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Cancer Pathology Registry

2003-2004

And Time Trend Analysis

Nadia Mokhtar

Chairman & Professor of Pathology

National Cancer Institute

Cairo University

Iman Gouda Iman Adel

Lecturer of Pathology Lecturer of Pathology

National Cancer Institute National Cancer Institute

Cairo University Cairo University

Department of Pathology, NCI

2007

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Preface

Histopathological data are important and mandatory to accurate cancer registration. Cancer Pathology Registry was originally developed by the Department of Pathology at the National Cancer Institute (NCI) since 1985. NCI of Cairo University is a large referral center draining the Cairo Metropolitan area as well as other parts of the country. The hospital receives a big number of patients, of which about 80% are presented to the Department of Pathology for tissue diagnoses. This material includes tissue biopsies, surgical specimens and referred slides and constructs the basis of this registry. Thus, such data have the advantage of establishing a model for hospital-based cancer registry founded on confirmed tissue diagnoses with detailed tumor typing, grading and pathologic staging.

Our data included all cases presented to the Department of Pathology, Surgical Pathology Unit during the years 2003-2004 with active participation of all the team members of this Unit. Their scientific experience and professional accurate diagnoses shaped the keystone of this work. The unified extended use of the International Histological Classification of Tumors by the WHO, and the ICD-O coding system applied in this registry may help towards a great degree of standardization and hence better comparability with other international registries. The implication of both coded and descriptive database computer system proved to be both practical and efficient. Leukemia data were kindly supplied by the Department of Clinical Pathology at NCI, headed by Professor Azza Kamel.

The material of this book could be of help to oncologists, post-graduate students and researchers in the field of cancer in general and cancer pathology in particular. Comparison with our previous Cancer Pathology Registry issued in 1991, provides a model for time trend analysis in cancer profile at large. This book also presents comparative features with other cancer registries from Egypt, namely a hospital-based cancer registry issued by the Department of Statistics and Cancer Epidemiology at NCI and the Gharbia population-based Cancer Registry issued by the Ministry of Health & Population.

The computer-aided database system was provided by the Department of Statistics & Cancer Epidemiology at NCI under supervision of Professor Inas El-Attar, chairman of the Department. She thankfully offered data from the NCI registry. Special thanks are due to Professor Amal Sami Ibrahim, Professor of Statistics and Cancer Epidemiology at NCI for granting data from the Gharbia Cancer Registry.

Professor Mohamed Hussein, Professor of Community Medicine at Faculty of Medicine Cairo University, enriched this registry book with a Chapter on epidemiology describing important comparative data and offering possible justifications for time trend changes. He provided expert suggestions for data presentation.

Dr. Atef Badran, the clinical data manager at NCI, gratefully compiled this book. He demonstrated skilled table and graphic designs. His effort, dedication and dexterity are greatly appreciated.

The editors wish to express gratitude to Professor Hussein Khaled, Dean of NCI and Professor of Medical Oncology for his enthusiasm and helpful ideas. His full support aided in launching this registry book.

This publication was funded by the National Cancer Institute and Sanofi Aventis. It is distributed free of charge.

The Editors

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Preface

Cancer is a global problem. It comes next to cardiovascular diseases as the cause of mortality of mankind. In Egypt, cancer morbidity and mortality are becoming increasingly important health problems. However, a national cancer registry is not available although many efforts are on the way to create such an essential development. An example is the Gharbia Governorate cancer registry headed by Prof. Amal Sami Ibrahim.

The National Cancer Institute, which is the largest comprehensive cancer center in the region, has been a pivotal corner in such efforts since the early 1970s starting with the cancer profile of Cairo Metropolitan Area. In addition to this, the hospital based cancer registry of our institute is being updated every year, and the latest for 2002 – 2003 is to be available soon.

Over the last 20 years, great efforts within the Department of Pathology have also been conducted by professor Nadia Mokhtar and colleagues, not only to evaluate the profile of cancer cases coming to be managed at the NCI, but also to study in depth the different clinicopathologic criteria of such cases. The previous Cancer Pathology Registry was one of the pioneer works in that field.

In this latest edition of the Cancer Pathology Registry, you will observe how cancer frequencies and patterns are changing over the years. I feel deeply indebted and thankful to Professor Nadia Mokhtar, Dr. Iman Gouda and Dr. Iman Adel from the Department of Pathology for their professional and detailed informative work. Now this book is a part of the oncology data base that is greatly needed for every oncologist in Egypt, the region and the rest of the world.

Professor Hussein Khaled

Dean of NCI

and Professor of Medical Oncology

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Members of the Department of Pathology

Surgical Pathology Unit

National Cancer Institute

Cairo University

Professor Hassan Nabil Tawfik

Professor Nabil El-Bolkainy

Professor Saad Eissa

Professor Nadia Mokhtar

Professor Nader Dahaba

Professor Nayera Anwar

Professor Magda Murad

Professor Sumaya El-Huseiny

Professor Hala Taha

Professor Mustafa El-Kabany

Professor Amani El-Deeb

Dr. Akram Nouh

Dr. Hoda Ismail

Dr. Amani Abdel Hamid

Dr. Mona Sakr

Dr. Wael Tharwat

Dr. Iman Gouda

Dr. Iman Adel

Dr. Tarek El-Bolkainy

Dr. Asmaa Salama

Dr. Iman Loay

Dr. Dina Salah

Dr. Nevine Fayez

Dr. Safinaz Talaat

Dr. Mohab Eissa

Dr. Ghada Abdel Salam

Dr. Iman Naguib

Dr. Hanaa Ebrahim

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No matter how good you may seem,

You’re always better in a team.

Nadia Mokhtar

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Table of Contents

	Chapter
1	General Features Of Total Pathology Series
2	Epidemiology
3	Malignant Urinary System Tumors
4	Breast Cancer
5	Lympho-Hematopoietic System Tumors
6	Malignant Digestive System Tumors
7	Malignant Respiratory System Tumors
8	Malignant Female Genital System Tumors
9	Malignant Skin Tumors
10	Soft Tissue Sarcomas
11	Malignant Bone Tumors
12	Malignant Endocrine System Tumors
13	Malignant Male Genital System Tumors
14	Malignant Central Nervous System Tumors
15	Malignant Eye And Ear Tumors
16	Multiple Malignant Tumors
17	Locally Recurrent Tumors
18	Metastatic Tumors At Initial Presentation With Unknown Primary
19	Metastatic Recurring Tumors
20	Tumors Of Border-Line Malignancy

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Chapter 1

General features of total Pathology series

Introduction

The Department of Pathology at NCI is built up of three units: 1. Surgical Pathology Unit, concerned with histopathologic diagnosis of cases presented to the NCI using recent tools and research facilities; 2. Cytology Unit, concerned with cytology diagnosis of cases; 3. Tissue Culture and Cytogenetics Unit, concerned mainly with advanced research activities. The material of this book represents all cases received by the Surgical Pathology Unit during the two-year period 2003-2004. Such material represents about 80% of the cases presented to the NCI during the same period of time (Table 1.1).

Time trend data compares the present series with our previous Cancer Pathology Registry including data of the 80’s and issued in 1991. Demographic data compares age and sex distribution of this recent series with our previous registry. Comparison with other hospital-based and population-based registries from Egypt is also presented.

Table 1.1: Percentage of New cancer cases who visited NCI, 2003-04

	2003 %	2004 %	2003-04 %
Histopathology diagnosis	79.6%	79.7%	79.6%
Non-histopathology diagnosis	20.4%	20.3%	20.4%

Figure 1.1: New cancer cases who visited NCI, 2003-04

Material of study

During the years 2003-2004, the Surgical Pathology Unit has received a total number of 20081 cases distributed as follows: biopsies 9113 cases (45.38%), surgical specimens 6378 cases (31.76%), and referred slides 4590 cases (22.86%). A total of 2638 cases were cancelled because of double registration due to biopsy or slide revision and specimen material. For double registered cases, only information from specimens' material was considered (Table 1.2). The rest of material (17443 cases) formed the core of data presented (Table 1.3). Non-malignant cases were presented only as main categories. Primary malignant solid tumors formed more than half of all categories (8437 cases). This group of new cancer cases, included cases of carcinoma in-situ, invasive cancer, and multiple tumors in the same site and in different sites, tumors with direct spread from an adjacent site, tumors not certain whether primary or secondary, as well as metastases at initial presentation with unknown primary.

A total of 1371 new leukemia cases were received by the Department of Clinical Pathology during the same period of time 2003-04. The leukemia cases summed to the primary malignant solid tumors formed a total of 9808 cases. This combined group formed the database to represent the relative frequency data of the Cancer Pathology Registry. A total of 805 recurrent and relapsing tumors and 218 tumors of borderline malignancy were presented separately.

Table 1.2: Total material received

	No.	%
Material included	17443	86.86
Double registered (cancelled)	2638	13.14
Total received	20081	100.00

The information was coded for computer data entry using the ICD-O coding system, while the topographic code was recorded using a coding system originally designed by Professor Nabil El-Bolkainy, Professor of Pathology and former Dean of NCI. Coded data were retrieved from the Surgical Pathology computer network and included the following items: hospital number, age, sex, pathology number, nature of specimen, type of operation, site or topography, morphologic diagnosis, grade, stage, surgical margin, lymph node status, etiology, secondary site, and category. Data concerning leukemia cases were retrieved from the Biostatistics and Cancer Epidemiology Department based on the records of the Department of Clinical Pathology.

The presented profile concerning the changing pattern of cancer and time trend analysis was performed by comparing the data base coded and descriptive parameters with similar parameters from the prior Cancer Pathology Registry issued by us in 1991. Time interval between both registries was about 15 years.

General Features of Total Series

The frequency distribution of all documented categories including the non-malignant cases showed a high predominance of malignant tumors constituting a majority of 53.16% (Table 1.3, Figures 1.2 and 1.3). This high figure is expected in cancer hospitals. The NCI receives referred cases from various regions of the country.

Table 1.3: Percent distribution of categories – 17443 cases

Category	%
I. Malignant tumors	53.16
Malignant primary site	48.38
Local recurrence	3.00
Metastatic recurrence and relapse	1.53
Uncertain primary or secondary	0.25
II. Borderline malignancy	1.25
III. Benign tumors	7.23
IV. Tumors of unpredictable biological potential	0.45
V. Premalignant lesions	2.37
Dysplasia	1.40
Atypical lesion	0.97
VI. Non neoplastic lesions and other conditions	35.54
Inflammatory	9.88
Non-neoplastic (NOS)*	6.19
Hyperplasia	6.13
Inadequate sample	4.88
For further data	2.85
Normal appearance	1.70
No definite diagnosis	1.64
Degenerative	1.03
Developmental malformation	0.40
Dysfunctional	0.30
Metaplasia	0.28
Immunologic disorder	0.26

*NOS: not otherwise specified

Figure 1.2: Percent distribution of categories – 17443 cases

Figure 1.3: Percent distribution of categories of malignant tumors

Table 1.4: Ranking of some important malignant tumors

Site	Rank	Number	Percent
Breast	1	1718	17.50
Leukemia	2	1371	13.95
Bladder	3	1201	12.22
Lymphoma	4	1146	11.66
Colon and rectum	5	427	4.34
Oral cavity and oropharynx	6	282	2.87
Lungs and pleura	7	233	2.37
Stomach	8	208	2.12
Liver and biliary tract	9	178	1.81
Larynx	10	174	1.77
Cervix	11	169	1.72
Esophagus	12	141	1.43
Ovaries	13	135	1.37
Corpus uteri	14	108	1.10
Prostate	15	47	0.48
Pancreas	16	41	0.42

Lymphoid tumors of different organs were incorporated in the lymphoma chapter

Figure 1.4: Ranking of malignant tumors

The ranking of 16 important malignant tumors internationally identified is shown in table 1.4 and figure 1.4. Breast cancer constituted 17.5% ranking as No. 1, followed by leukemia, bladder cancer and lymphoma as ranks 2, 3 and 4 respectively. This is different from WHO reports showing that lung, colorectal, and stomach cancers are the most common cancers in both industrialized and developing countries. Lung and pleura cancer in our series ranked as number 7 and colorectal cancer as number 5 while stomach ranked as number 8. Among men, prostate cancer is largely seen in developed countries. But in our series prostate cancer is low and bladder cancer is high. For women, the most common cancers worldwide are breast and cervical cancer, although cervical cancer is primarily seen in less developed countries. In our series breast cancer is the most common tumor, keeping in accordance with worldwide figures, however, cervical cancer is low. The unique feature of our series is the high prevalence of bladder cancer, breast and lympho-hematopoietic malignancies.

Table 1.5: Sex distribution of malignant primary tumors

in different systems-9808 cases

Site	Male		Female		Total
	No.	%	No.	%	No.	%
Lympho-hematopoietic system	1641	65.20	876	34.80	2517	25.67
Breast	26	1.50	1692	98.50	1718	17.50
Urinary system	991	74.85	333	25.15	1324	13.50
Digestive system	721	54.62	599	45.38	1320	13.45
Respiratory system	422	73.00	156	27.00	578	5.90
Female genital system	0	0.00	461	100.00	461	4.70
Skin	224	61.20	142	38.80	366	3.74
Soft tissue	161	60.07	107	39.93	268	2.74
Endocrine system	102	46.58	117	53.42	219	2.23
Bone	120	63.83	68	36.17	188	1.92
Male genital system	95	100.00	0	0.00	95	0.97
Central nervous system	38	50.00	38	50.00	76	0.77
Special senses	8	50.00	8	50.00	16	0.16
NOS	320	48.34	342	51.66	662	6.75
Total	4869	49.65	4939	50.35	9808	100.00

Figure 1.5: Sex distribution of malignant solid tumors

Table 1.6: Age distribution of malignant primary tumors

in different systems-9808 cases

Site	Adults		Pediatrics		Total
	No.	%	No.	%	No.	%
Breast	1718	100.00	0	0.00	1718	17.50
Lympho-hematopoietic system	1691	67.18	826	32.82	2517	25.67
Urinary system	1273	96.15	51	3.85	1324	13.50
Digestive system	1275	96.59	45	3.41	1320	13.45
Respiratory system	570	98.62	8	1.38	578	5.90
Female genital system	450	97.61	11	2.39	461	4.70
Skin	348	95.08	18	4.92	366	3.74
Soft tissue	193	72.00	75	28.00	268	2.74
Endocrine system	146	66.66	73	33.44	219	2.23
Bone	85	45.20	103	54.80	188	1.92
Male genital system	90	94.74	5	5.26	95	0.97
Central nervous system	41	54.44	35	45.56	76	0.77
Special senses	12	75.00	4	25.00	16	0.16
NOS	608	91.84	54	8.16	662	6.75
Total	8500	86.66	1308	13.34	9808	100.00

Figure 1.6: Age distribution of malignant primary tumors (number of cases)

Table1.5 and figure 1.5 represent the relative frequency of malignant tumors of the different systems with sex distribution, while table 1.6 and figure 1.6 show age distribution. They show high incidence of lympho-hematopoietic, breast, digestive, urinary, and respiratory systems as the 5 most common systems.

Sex distribution; The male to female ratio in the whole series was 1:1.01 reflecting the large bulk of female breast cancer. In males, the lympho-hematopoietic system represented the highest figure of 33.70%, followed by the urinary system 20.35% and the digestive system 14.80% as seen in table 1.8. In females, however, the highest figure was that of the breast 34.26%, followed by the lympho-hematopoietic system 17.74%, the digestive system 12.13%, and the female genital system 9.33%. Table 1.9 shows the ranking of female malignancies in different systems. Comparative ranking between male and female malignancies is demonstrated in figure 1.5.

Table 1.8: Ranking of male malignant tumors- 4869 cases

Site	Rank	Number	Percent
Lympho-hematopoietic system	1	1641	33.70
Urinary system	2	991	20.35
Digestive system	3	721	14.80
Respiratory system	4	422	8.67
Skin	5	224	4.63
Soft tissue	6	161	3.30
Bone	7	120	2.46
Endocrine system	8	102	2.10
Male genital system	9	95	1.95
Central nervous system	10	38	0.78
Breast	11	26	0.53
Special senses	12	8	0.16
NOS		320	6.57

Figure 1.8: Ranking of male malignant tumors

Table 1.9: Ranking of female malignant tumors- 4939 cases

Site	Rank	Number	Percent
Breast	1	1692	34.26
Lympho-hematopoietic system	2	876	17.74
Digestive system	3	599	12.13
Female genital system	4	461	9.33
Urinary system	5	333	6.74
Respiratory system	6	156	3.16
Skin	7	142	2.90
Endocrine system	8	117	2.36
Soft tissue	9	107	2.16
Bone	10	68	1.37
Central nervous system	11	38	0.77
Special senses	12	8	0.16
NOS		342	6.92

Figure 1.9: Ranking of female malignant tumors

Age distribution; The total primary malignant tumors were divided into 2 groups; namely adults and pediatrics. The adult group constituted a majority of 86.66% of cases. In this group, breast cancer represented alone 20.20%. The lympho-hematopoietic system, digestive system, and urinary system came next in frequency being 19.90%, 15.00%, and 14.98% respectively. The pediatric group formed a minority of 13.34%, 63.15% of which were in the lympho-hematopoietic system. Bone and soft tissue tumors constituted 7.87% and 5.73% respectively. Tables 1.10, 1.11 and corresponding figures show the ranking of adult and pediatric tumors in different systems respectively.

Table 1.10: Ranking of adult malignant tumors-8500 cases

Site

Rank

Number

Percent

Breast	1	1718	20.21
Lympho-hematopoietic system	2	1691	19.90
Digestive system	3	1275	15.00
Urinary system	4	1273	14.98
Respiratory system	5	570	6.71
Female genital system	6	450	5.29
Skin	7	348	4.10
Soft tissue	8	193	2.27
Endocrine system	9	146	1.72
Male genital system	10	90	1.06
Bone	11	85	1.00
Central nervous system	12	41	0.48
Special senses	13	12	0.14
NOS		608	7.14

Figure 1.10: Ranking of adult malignant tumors

Table 1.11: Ranking of pediatric malignant tumors-1308 cases

Site	Rank	Number	Percent
Lympho-hematopoietic system	1	826	63.15
Bone	2	103	7.87
Soft tissue	3	75	5.73
Endocrine system	4	73	5.58
Urinary system	5	51	3.90
Digestive system	6	45	3.44
Central nervous system	7	35	2.68
Skin	8	18	1.38
Female genital system	9	11	0.84
Respiratory system	10	8	0.61
Male genital system	11	5	0.38
Special senses	12	4	0.31
NOS		54	4.13

Figure 1.11: Ranking of pediatric malignant tumors

Table 1.12 and figure 1.12 compare two Cancer Pathology Registries. There is increased relative frequency of breast and lung cancers and decreased relative frequency of bladder cancer in the present series.

Table 1.12: Time trend of cancer pathology registries

Site	CPR 2003/2004		CPR 1985-1989
	%	Rank	%	Rank
Breast	17.50	1	11.34	3
Leukemia	13.95	2	6.79	5
Bladder	12.22	3	26.39	1
Lymphoma	11.66	4	12.23	2
Colon and rectum	4.34	5	5.05	6
Oral cavity and pharynx	2.87	6	7.62	4
Lungs and pleura	2.37	7	0.58	13
Stomach	2.12	8	3.06	8
Liver and biliary tract	1.81	9	2.63	9
Larynx	1.77	10	1.04	11
Cervix	1.72	11	3.58	7
Esophagus	1.43	12	1.83	10
Ovaries	1.37	13	0.80	12
Corpus uteri	1.10	14	0.53	14
Prostate	0.48	15	0.32	15
Pancreas	0.42	16	0.13	16

Figure 1.12: Time trend of Cancer Pathology Registries

Table 1.13 and figure 1.13 compare the present registry series with 2 other registry series, from the Department of Biostatistics & Cancer Epidemiology at NCI and from the population-based Gharbia Governorate Cancer Registry. The 3 Egyptian registries, in spite of some differences, all agreed on frequent cancers. The minor differences among the three registries can be justified by the nature of the material collected, geographical differences, and the followed protocols of management.

Table 1.13: Relative frequency of common sites of cancer in different registries

Site	CPR 2003/2004	NCIR 2003/2004	GCR 1999
Breast	17.5%	18.9%	18.6%
Bladder	12.2%	10.1%	9.5%
Lymphoma	11.6%	8.1%	9.5%
Colon and rectum	4.3%	4.4%	3.8%

CPR: Cancer Pathology Registry, NCIR: National Cancer Institute Registry (Department of Biostatistics & Cancer Epidemiology), GCR: Gharbia Cancer Registry.

Figure 1.13: Relative frequency of common sites of cancer

in different registries

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Chapter 2

Epidemiology

Epidemiologic Implications of the NCI Cancer Pathology Registries Between 1985-89 and 2003-04

By comparing the two period's pathology registries, it was noticed that the yearly pathologically examined cases dropped by 9% during this 15-year interval. This drop was due to the appreciable decrease in number of male pathological specimens. On the other hand female pathological specimens showed slight increase during the 15-year interval (Table 2.1).

Table 2.1: Average number of solid malignant tumors per year

Sex	1985-89	2003-04
Males	2647	2026
Females	1976	2182
Total	4623	4208

Before investigating the reasons for this noticeable drop in pathologically examined cases with the accompanying different sex behavior, it is important to consider the other important factors that changed over the same time interval. Despite NCI being the main cancer treating center in Egypt, yet since the mid 1990's other cancer management centers were established by other Universities as well as Ministry of Health and Population in many geographical areas of the country. Also, mix of cases and protocols of management including other non-histologic tests for diagnosis has changed over the years. These two factors may explain some of the appreciable drop in the number of pathologically confirmed cases at the Department of Pathology at NCI. Table 2.2 shows that not only the absolute number of pathologically examined cases had dropped, but also the drop was more in relation to the increased population size during the 15- year interval. The overall estimate of yearly incidence index for males was 107.8 cases, diagnosed by pathology at the NCI per million Egyptians during the 1980's period. The yearly incidence estimate halved to 51.9 male malignancies per million male populations during 2003-04.

Table 2.2: Pathologically examined cases in relation to Egyptian population

	Population size		Cases / million population
Sex	1986 census 1985-1989	2003 estimation 2003-2004	1985-1989	2003-2004
Males	24 710 000	34 444 000	107.8	51.9
Females	23 545 000	32 869 000	84.3	62.6

If the Department of Pathology at NCI was the only place for malignancy diagnosis then this would represent true drop in incidence of malignant tumors for both sexes. However, these proportions shown in Table 2.2 could not be taken as true incidence rates or even an approximation. It is used as indicators of changes of confirmed cases in relation to population size, to correct for increasing population.

Figure 2.1: Pathologically examined male cases in relation to Egyptian male population (annual incidence rate)

There was a drop in the population related rates of pathologically diagnosed male cases in most systems as seen in Figure 2.1. The most appreciable rate of decrease was noticed for cancer of the urinary system. This dramatic drop in urinary system malignancy rate was mostly due to drop in average number of yearly diagnosed bladder cancer cases. This could be a real decrease in Egyptian bladder cancer cases. The pathology details that are shown later in the Chapter on urinary system may give some clue to the probable decrease of the schistosoma related type.

It is important to note that the general ranking of the systems was the same for the two periods. In other words, the urinary system malignancies are the most common among males, and the brain malignancies showed the lowest occurrence. Every male pathological specimens by site in relation to male population showed that the rate for 2003–04 was almost half the rate for 1985-89. This rate drop was most noticeable in the urinary system malignancy where it dropped to one third.

The estimated age specific incidence rates, as seen in figure 2.2, showed continuous increase starting after the age of 25 years, which is more noticeable after the age of 45 years. In the recent period 2003-04, the rates continued to increase after the age of 60 years which was not noticed during the 1980's data. This last finding may be due to longevity of the population (increased life span) which leads to more old age males who are at higher risk of malignancy. However, this old age increase of incidence may also be due to more awareness of the public towards their health status and improved health care seeking behavior.

Figure 2.2:Annual age specific estimate of incidence rate for male malignancies

Figure 2.3: Pathologically examined female cases in relation to Egyptian female population (annual incidence rate)

Female malignant cases in relation to Egyptian female population showed appreciable increase in the recent time period for breast cancer. In contrast to males, the relative distribution of system malignancies was different in recent than old time period, e.g. digestive system stepped up from the third to the second position, while female genital system stepped down from rank 2 to rank 3.

Female estimated overall yearly malignancy incidence index dropped from 84.3 to 62.6 cases per one million Egyptian female population between 1985-89 and 2003-04.

The estimate of incidence rates of the ages between 20 years and 50 years showed an exponential increase for both time periods. During the early period of the 1980's estimates of incidence rates before the age of 60 were higher then those of the 2003-04 time period. After the age of 60, female annual incidence rates showed increase during recent time period, as compared to the 1980's period (Figure 2.4). This may explain changing of health care seeking behavior among females in older ages. However, the cohort of living Egyptian women who are older than 70 years seemed to still keep the tradition of negligence of seeking health care.

Detailed and careful analysis of site-specific rates should be done to understand whether this changing pattern is true or apparent due to changes in female health seeking care attitudes.

Figure 2.4: Annual age specific estimate of incidence rate for

female malignancies

Epidemiologic Aspects of Urinary Bladder Cancer

The annual urinary bladder pathologically recorded cases dropped in recent years as compared to earlier ones, from 862 cases per year in 1985-89 to 600 cases in 2003-04. However, this drop in cases was similar for males and females as shown by the stable slightly changed sex ratio. This Male to Female ratio showed that male urinary bladder pathological cases were more than three times those among females (Table 2.3).

Table 2.3: M:F ratios in bladder cancer

Period	M:F case ratio	M:F incidence ratio
1985-89	3.8	3.7
2003-04	3.5	3.3

The majority of cases in both sexes showed that squamous cell carcinoma and transitional cell carcinoma together constituted around 90% of all pathological types. The squamous carcinoma was the highest in 1985-89 then it gave way to the transitional carcinoma in the recent time period (Figures 2.5 and 2.6).

Figure 2.5: Relative frequency of histopathologic types of urinary bladder cancer in male patients

Figure 2.6: Relative frequency of histopathologic types of urinary bladder cancer in female patients

It is noticed that females showed less relative frequency (proportion to all cases) drop for squamous type than males between the two time periods. Females dropped by one third while males dropped by one half. Many Egyptian studies incriminate schistosomiasis as a high risk for development of urinary bladder malignancy especially the squamous type. Accordingly, it is tempting to suggest that female reluctance to seek early diagnosis and treatment of schistosomiasis increases the chances of pathological sequels including squamous bladder malignancy.

As seen in figures 2.7 the age distribution of bladder cancer cases in males is very similar to that of the overall malignancy that was shown in figure 2.2. Figure 2.8 illustrates the previously mentioned low health care seeking behavior of the old aged women.

More than three quarters of the transitional cell carcinoma were above the age of 50 years (79%). In contrast, the squamous cell carcinoma shows lower proportion of cases occurring above the age of 50 years, only 57%.

Figure 2.7: Annual age specific estimate of incidence rate of urinary bladder cancer in male patients

Figure 2.8: Annual age specific estimate of incidence rate of urinary bladder cancer in female patients

Epidemiologic Aspects of Breast cancer

Figure 2.9 shows that female breast cancer incidence was similar for the two periods until the age of 45 years. Starting from the age of 50 years and above, the pathologically registered cases for the later period 2003-04 showed markedly higher rates.

This pattern of age incidence may suggest age misreporting during the earlier period 1985-89 especially around the ages of 30-39 years and older than 50 years. However, more in depth epidemiologic studies need to be done for this seemingly increasing type of malignancy. These studies should include hormonal, environmental and maybe genetic epidemiology. For example; the drop in incidence after menopause could be in line with the hormonal etiology hypothesis.

The female to male ratio of breast cancer has shown a 3-fold increase from 23.7 in 1985-89 to 72.8 in 2003-04.

Figure 2.9: Annual age specific estimate of incidence rate of breast cancer in female patients

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Chapter 3

malignant Urinary system tumors

The urinary system malignancies represented a high incidence of 13.50% of total malignant tumors. The main bulk was dominated by the urinary bladder cancer, 12.22%. The rest of the urinary system malignancies constituted a minority of only 1.27%. Table 3.1 and figure 3.1 show the relative frequency of malignant tumors of the urinary system.

Table 3.1: Urinary system malignancies – 1324 cases

Site	No.	%	%Total
Urinary bladder	1201	90.71	12.22
Kidney	118	8.91	1.22
Ureter	4	0.30	0.05
Urethra	1	0.08	0.01
Total	1324	100.00	13.50

Figure 3.1: Percent distribution of urinary system malignancies – 1324 cases

Urinary bladder

The total number of bladder cancer cases was 1201. The material received at the Department of Pathology for cases of bladder cancer was distributed as follows: surgical specimens, TUR and biopsies constituted 86.1%, while referred slides constituted 13.9%. After excluding referred cases (13.9%), the nature of the surgical material received at the Department of Pathology was as follows: radical operations done for bladder cancer at NCI, whether radical cystectomy or anterior pelvic excentration represented 44.29% of the bladder cancer surgical material. Cystectomy whether subtotal or not otherwise specified (NOS) represented 1.55%. TUR procedure was mostly performed for transitional cell carcinomas, and represented 17.12%. Biopsies were 37.04%. Table 3.2 and figure 3.2 show the nature of material for bladder cancer submitted from the Department of Surgery at NCI, excluding cases with referred slides only.

Table 3.2: Surgical material for bladder cancer at NCI- 1034 cases

Nature	Transitional		Squamous		Adeno.		Undifferent.		Total
	No.	%	No.	%	No.	%	No.	%	No.	%
Radical specimens	229	34.18	196	65.55	22	53.66	11	45.83	458	44.29
Cystectomy (Subtotal or NOS)	9	1.34	5	1.67	2	4.88	0	0	16	1.55
TUR	156	23.28	17	5.69	2	4.88	2	8.33	177	17.12
Biopsy	276	41.19	81	27.09	15	36.59	11	45.83	383	37.04
Total	670		299		41		24		1034

*Cases with referred slides only were not included.

Figure 3.2: Surgical material for bladder cancer at NCI- 1034 cases

The age group showed that the highest frequency in bladder cancer was 61-70 years (30.38%) followed by 51-60 years (29.94%). There was a male to female predominance of 3.5:1. It is worthwhile to mention that the male to female ratio varied within the histopathologic types, being almost 2:1 in adenocarcinoma and squamous cell carcinoma, 7:1 in papillary transitional cell carcinomas, while the non-papillary transitional carcinomas matched the 4:1 ratio of bladder carcinomas in general.

Multiple tumors were seen in 5.81% of carcinomas, the majority (2/3) were transitional cell carcinomas. The relative frequency of histopathologic subtypes of malignant tumors as seen in table 3.3 and figure 3.3 demonstrate a predominance of transitional cell carcinomas (64.20%). The invasive non-papillary type of transitional cell carcinomas was the most common (61.68%) followed by the papillary type with no evidence of invasion of the basement membrane (22.09%), and then the papillary & superficially invasive type (16.23%).

Table 3.3: Histopathologic types of bladder cancer, both sexes – 1201 cases

Type	No.	%
Transitional cell carcinoma	771	64.20
Squamous cell carcinoma	340	28.30
Verrucous squamous carcinoma	5	0.42
Adenocarcinoma	54	4.50
Undifferentiated carcinoma	25	2.08
Embryonal rhabdomyosarcoma	4	0.33
Leiomyosarcoma	2	0.17
Total	1201	100.00

Figure 3.3: Histopathologic types of bladder cancer – 1201 cases

Proper evaluation of pathologic stage was done in 610 cases of common bladder carcinomas. Their distribution as seen in table 3.4 and figure 3.4 demonstrated nearly equal numbers of early (Pa & P1) and late stages (P3 & P4). The early stage tumors were mostly of the transitional type.

Table 3.4: Percent staging of common bladder carcinomas

- surgical specimens – 610 cases

Stage	Transitional		Squamous		Total
	No.	%	No.	%	No.	%
Pa	23	5.70	0	0	23	3.78
P1	173	42.82	18	8.80	191	31.32
P2	64	15.84	48	23.30	112	18.40
P3	117	28.96	109	52.90	226	37.00
P4	27	6.68	31	15.00	58	9.50
Total	404	100.00	206	100.00	610	100.00

Figure 3.4: Staging of common bladder carcinomas – 610 cases

Table 3.5 and figure 3.5 demonstrate an increase in relative frequency of transitional cell carcinoma and decrease in squamous cell carcinoma in both sexes collectively. Detailed epidemiologic pattern regarding the change of histopathologic types in each sex is documented in Chapter 2. Other tumor types show stable relative frequency.

Table 3.5: Time trend of bladder cancer pathology types illustrated

by two Cancer Pathology Registries

Type	CPR 2003-2004	CPR 1985-1989
	%	%
Squamous cell carcinoma	28.72	58.45
Ordinary	28.30	55.95
Verrucous	0.42	2.50
Transitional cell carcinoma	64.20	30.89
Adenocarcinoma	4.50	5.49
Undifferentiated carcinoma	2.08	4.69
Sarcomas & unclassified	0.50	0.48

Figure 3.5: Time trend of bladder cancer pathology types illustrated

by two Cancer Pathology Registries

In the recent Cancer Pathology Registry, there were trends for more superficial tumors and less invasive stage (Table 3.6 and Figure 3.6). The difference between the old and recent series with regard to the general profile of bladder cancer is shown in table 3.7.

Table 3.6: Time trend of bladder cancer pathologic stage illustrated

by two Cancer Pathology Registries

Pathologic stage	CPR 2003-2004	CPR 1985-1989
	%	%
Pa	3.78	0.2
P1	31.32	7.6
P2	18.40	6.0
P3	37.00	69.5
P4	9.50	16.7

Figure 3.6: Time trend of bladder cancer pathologic stage illustrated

by two Cancer Pathology Registries

Table 3.7: Time trend for bladder cancer in two Cancer Pathology Registries

Years	CPR 2003/2004	CPR 1985-1989
Rank Average yearly cases	3 600	1 797
Percent total malignancy	12.22	26.39
Median age in years	60	50
Percent cases with bilharzia ova in specimen	39.7	61.7
Percent histopathology types Squamous carcinoma Verrucous carcinoma Transitional carcinoma	28.7 0.4 64.2	58.5 2.5 30.9
Percent stage Superficial P0-P1 Deep P2-P4	35.1 64.9	7.8 92.2
Percent lymph node metastasis	27.07	25.8

Lymph nodes were positive for metastasis in 27.07% of cases. The incidence of lymph node metastasis was higher with invasive transitional cell carcinomas (61.11%) in contrast to the other types which showed collectively a 38.89% incidence of lymph node metastasis. Dissected lymph nodes ranged mostly between 1 and 10 in number (49.06%) while specimens with 11 to 20 lymph nodes formed 40.82% and those with 20 or more lymph nodes formed 9.36%.

Bilharziasis was demonstrated as ova deposition in tissues in 39.7% of cases. Among the squamous cell carcinomas, bilharziasis was evident in about half of the cases (51.73%), while it was evident in 33.60% of transitional cell carcinomas.

Malignant Renal Tumors

The total number of cases was 118 representing nearly 1.2% of total malignancies. The frequency distribution of the different histopathologic types is shown in table 3.8 and figure 3.7.

Table 3.8: Histopathologic types of malignant renal tumors – 118 cases

Type	No.	%	% Total
Renal cell carcinoma	67	56.78	0.68
Wilms' tumor	44	37.28	0.45
Transitional cell carcinoma	5	4.24	0.05
Squamous cell carcinoma	1	0.85	0.01
Primitive neuroectodermal tumor (PNET)	1	0.85	0.01
Total	118	100.00	1.2

Figure 3.7: Percent distribution of histopathologic types

of malignant renal tumors

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chapter 4

Breast Cancer

Breast cancer came as number 1 in ranking of malignant tumors constituting 17.50% of total malignancies. Duct carcinomas formed a majority of 85.02%, 2.04% of which were intraductal carcinomas. Lobular carcinomas formed 5.81%, while less common carcinomas formed collectively 8.42%. Malignant phyllodes tumors constituted 0.41% while sarcomas of the breast and Non-Hodgkin's lymphomas formed 0.17% each (Table 4.1). The relative frequency of histopathologic types of breast tumors is shown in table 4.2 and figure 4.1. Multiple tumors formed 4.14% and were mostly duct carcinomas (80.70%). As regard the laterality of tumors, 26.58% had no specified laterality. A slight insignificant predominance of the left side tumors was noticed, being 37.59%, while right side tumors were 34.88%, and bilateral tumors were only 0.78%.

Table 4.1: Malignant tumors in breast– 1721 cases

Tumor	No.	%
Breast tumors	1718	99.83
Lymphoid tumors	3	0.17
Total	1721	100.00

Table 4.2: Histopathologic types of malignant breast tumors – 1721 cases

Type	No.	%
Duct carcinoma	1463	85.02
Lobular carcinoma	100	5.81
Mixed duct and lobular carcinoma	53	3.08
Mucoid carcinoma	24	1.39
Duct carcinoma and Paget's disease	16	0.93
Medullary carcinoma	14	0.81
Metaplastic carcinoma	14	0.81
Cribriform carcinoma	9	0.52
Papillary carcinoma	5	0.29
Signet ring carcinoma	3	0.17
Paget's disease of nipple	2	0.12
Tubular carcinoma	2	0.12
Apocrine carcinoma	2	0.12
Inflammatory carcinoma	1	0.06
Malignant phyllodes tumor	7	0.41
Sarcoma	3	0.17
Non-Hodgkin's lymphoma	3	0.17
Total	1721	100.00

Figure 4.1: Percent distribution of histopathologic types of

malignant breast tumors

The age distribution showed rare occurrence of breast cancer in cases below the age of 30 (2.30%) and above the age of 80 (1.00%). Females showed a vast majority of 98.35%, while only 1.65% were males.

Pathologic grading of breast carcinomas with an assigned grade showed a low incidence of grade 1 tumors (0.88%). Grade 2 formed 84.00%, while grade 3 formed 15.12% (Figure 4.2).

Figure 4.2: Percent of pathological grading of breast cancer

Lymph nodes were positive for metastasis in 69.50% of cases. The incidence of lymph node metastasis was slightly higher with invasive duct carcinomas (70.25%) in contrast to the other types which showed collectively a 62.50% incidence of lymph node metastasis. Dissected lymph nodes ranged mostly between 11 and 20 in number (66.37%) while specimens with more than 20 dissected lymph nodes formed 19.05% and those with 10 or less lymph nodes formed 14.58% (Figure 4.3).

Figure 4.3: Number of lymph nodes dissected

Specimen types: Modified radical mastectomy specimens represented the majority of breast cancer surgical specimens forming 75.19%, while radical mastectomies formed 1.94%, mastectomy (NOS) 1.35%, and simple mastectomies 1.21%. Wide excision specimens constituted 5.08% and lumpectomy specimens 4.59%. The rest of specimens were biopsies, forming 10.64% (Figure 4.4).

Figure 4.4: Types of specimens for breast cancer cases

Hormone Receptors and Her-2 Status (Tables 4.3, 4.4, Figures 4.5 and 4.6): Tumors positive for estrogen and/ or progesterone receptors formed a slight predominance of 57.8%. While positive tumors for Her-2 oncogene formed a minority of 44.5%.

Table 4.3: Hormone receptor status in breast cancer cases

Receptor status	%
Positive hormone receptor(s)	57.80
ER+ & PR+	43.9
ER+ & PR-	8.9
ER- & PR+	5.0
Negative hormone receptors	42.20
Total	100

Figure 4.5: Percent distribution of hormone receptor status

in breast cancer cases

Table 4.4: Her-2 receptor status in breast cancer cases

Receptor status	%
Positive receptor (scores +2 & +3)	44.5
Negative receptor (scores 0 & +1)	55.5
Total	100

Time trend as seen from table 4.5 and figures 4.7 and 4.8 show increased relative frequency of breast cancer in the recent series, slight increase of intraduct carcinoma, smaller average tumor size, less high grade tumors and decreased frequency of lymph node metastasis

Figure 4.6: Percent distribution of Her2 receptor status

in breast cancer cases

Table 4.5: Time trend for breast cancer in two Pathology Registries.

Years	CPR 2003/2004	CPR 1985-1989
Rank (number of cases)	1 (N=1718)	3 (N=1713)
% Total malignancy	17.50	11.34
Average tumor size	3.2	4.5
% Most common tumor	Duct carcinoma 85.02%	Duct carcinoma 83.36%
% Intraduct carcinoma	2.04	1.5
Grades 1:2:3	0.88:84.00:15.12	5.40:66.02:28.57
% Bilaterality	0.78	0.60
% Male breast cancer	1.5	3.8
% Lymph node metastasis	69.50	75.29
% Conservative surgery	10%	Almost nil

Figure 4.7: Time trend for breast cancer in two Cancer Pathology Registries

Figure 4.8: Time trend for breast cancer in two Cancer Pathology Registries

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Chapter 5

Lympho-hematopoietic system tumors

During the years 2003-2004, the Department of Pathology received a total of 1146 lymphoma cases. They constituted 11.66% of total malignancies. During the same period of time, the Department of Clinical Pathology received a total of 1371 cases of leukemia, constituting 13.95% of total malignancies. The leukemia:lymphoma ratio was 1.2:1. While lymphoma predominated in adults, leukemia predominated in children (Table 5.1 and Figure 5.1). Males slightly predominated in lymphoma and females predominated in leukemia (Table 5.2 and Figure 5.2 ).

Table 5.1: Lympho-hematopoietic malignancies,

age distribution- 2517 cases

	Adult	Pediatric	Total
Lymphoma	948 (56.06%)	198 (23.97%)	1146
Leukemia	743 (43.94%)	628 (76.03%)	1371
Total	1691 (100%)	826 (100%)	2517

Figure 5.1: Lympho-hematopoietic malignancies, age distribution- 2517 cases

Table 5.2: Lympho-hematopoietic malignancies,

sex distribution- 2517 cases

	Males	Females	Total
Lymphoma	844 (51.43%)	302 (34.47%)	1146
Leukemia	797 (48.57%)	574 (65.53%)	1371
Total	1641 (100%)	876 (100%)	2517

Figure 5.2: Lympho-hematopoietic malignancies, sex distribution- 2517 cases

Lymphoid Malignancies

Malignant lymphoma cases showed a predominance of non-Hodgkin's lymphoma forming 76.6% of cases (Table. 5.3 and Figure 5.3).

Table 5.3: Lymphoid malignancies – 1146 cases

	Type	No.	%	% Total
	Non-Hodgkin’s lymphoma	878	76.6	8.95
	Hodgkin’s lymphoma	268	23.4	2.73
	Total	1146	100	11.6

Figure 5.3: Lymphoid malignancies (%)

Phenotyping done as a routine for all cases of lymphoma with available material constituted 90.43% of cases (Figure 5.4). Phenotyping is used to establish clonality, differentiate Hodgkin's from non-Hodgkin's lymphoma, and for sub-typing of non- Hodgkin's and Hodgkin’s lymphoma. There was a high predominance for B-phenotype lymphoma (Table 5.4 and Figure 5.6).

Table 5.4: Phenotyping of non- Hodgkin's lymphoma – 878 cases

	Type	No.	%
	B-cell NHL	712	81.08
	T-cell NHL	82	9.35
	Unspecified	84	9.57
	Total	878	100.00

Figure 5.4: Phenotyping of NHL (%)

The series showed a male to female predominance of 2.8:1. Adult lymphomas constituted 82.70% and pediatric lymphomas 17.3% (Table 5.5 and Figure 5.5).

Table 5.5: Adult and pediatric lymphomas – 1146 cases

Type	Adults		Pediatrics
	No.	%	No.	%
Non - Hodgkin's lymphoma	757	80.00	121	61.10
Hodgkin's lymphoma	191	20.00	77	38.90
Total	948	82.70	198	17.30

Figure 5.5: Adult and pediatric lymphomas

The relative frequency of non-Hodgkin's lymphoma subtypes according to the WHO classification is seen in table 5.6, figures 5.6 and 5.7. Extranodal presentation was seen in 23.23% of non-Hodgkin's lymphomas. They were registered with the lymphoid malignancies but their detailed presentation is demonstrated in the corresponding systems. The most common site was the gastrointestinal tract (Table 5.7 and Figure 5.8).

Table 5.6: Subtyping of non- Hodgkin's lymphoma – 878 cases

Type	No.	%	Average age	M/F ratio
B-cell lymphomas	712	81.08	44.5	3.1
Diffuse large cell lymphoma	479	54.55	47.2	1.4
Burkitt's lymphoma	60	6.83	7.7	4.5
Small lymphocytic lymphoma	51	5.80	52.0	4.8
Follicular lymphoma	45	5.13	48.4	2.3
MALT and marginal zone lymphoma	43	4.90	54.0	2.4
Myeloma and plasmacytoma	18	2.05	62.5	1.8
Mantle cell lymphoma	6	0.68	65.6	3.9
Hairy cell leukemia	6	0.68	44.0	3.1
Lymphoblastic B-cell lymphoma	3	0.34	27.0	3.4
Anaplastic B-cell lymphoma	1	0.12	37.0	-
T-cell lymphomas	82	9.35	46.6	2.3
Lymphoblastic T-cell lymphoma	36	4.10	10.7	3.0
Peripheral T-cell lymphoma	22	2.51	45.0	2.7
Anaplastic T-cell lymphoma	18	2.05	38.0	1.6
Mycosis fungoides	5	0.57	67.0	1.8
Angioimmunoblastic lymphoma	1	0.12	72.0	-
Unspecified phenotype	84	9.57	64.0	2.2
Total	878	100.00	51.7	2.5

Figure 5.6: Percent distribution of phenotypes of non- Hodgkin's lymphoma

T-Cell lymphomas

B-Cell lymphomas

Figure 5.7: Detailed subtyping of Non-Hodgkin’s lymphoma

Extranodal lymphomas

A total of 204 cases of extranodal lymphomas were diagnosed. The relative frequency in different systems is seen in table 5.7. More detailed description of their types and specific sites are demonstrated in the corresponding chapters.

Table 5.7: Extranodal lymphomas-

204 cases

Site	%
Gastrointestinal tract	45.56
Respiratory system	23.04
Bone	16.67
Skin	11.27
Endocrine system	1.48
Breast	1.48
Female genital system	0.50
Total	100.00

Figure 5.8: Extranodal lymphomas %

Hodgkin's Lymphomas

A total number of 268 cases of Hodgkin's lymphoma (23.4% of all lymphomas) were received during the years 2003-2004. Their sub-typing is seen in table 5.8 and figure 5.9.

Table 5.8: Subtyping of Hodgkin's lymphoma – 268 cases

Type	No.	%	Average age	M/F ratio
Classic Hodgkin's lymphoma	229	85.45	26.1	2.4
Mixed cellularity	123	45.90	24.0	2.7
Nodular sclerosis	85	31.72	24.2	1.7
Lymphocyte rich	13	4.85	28.4	2.5
Lymphocyte depletion	8	2.98	27.7	2.6
Nodular lymphocyte predominance	25	9.32	20.0	3.8
Unspecified	14	5.23	25.4	2.6
Total	268	100.00	25.0	2.7

Figure 5.9: Percent distribution of subtypes of Hodgkin's lymphoma

Pediatric Lymphomas

Pediatric lymphomas constituted 17.3% with a predominance of non-Hodgkin's lymphoma (Table 5.9 Figure 5.10). Burkitt's lymphoma was the most frequent subtype (Table 5.10 and Figure 5.11). With regards to Hodgkin's lymphoma, the most frequent subtype was mixed cellularity which comprised about half of the cases (Table 5.11, Figure 5.12).

Table 5.9: Pediatric lymphomas – 198 cases

	Type	No.	%
	Non-Hodgkin's lymphoma	121	61.10
	Hodgkin's lymphoma	77	38.90
	Total	198	100.00

Figure 5.10: Pediatric lymphomas (%)

Table 5.10: Pediatric non- Hodgkin's lymphomas – 121 cases

Type	No.	%
Burkitt's lymphoma	53	43.80
Lymphoblastic lymphoma	30	24.80
Diffuse large B-cell lymphoma	17	14.10
Peripheral T-cell lymphoma	3	2.50
Anaplastic large cell lymphoma	3	2.50
MALT lymphoma	2	1.60
Skin lymphomas	2	1.60
Unspecified	11	9.10
Total	121	100.00

Figure 5.11: Percent type distribution of pediatric non- Hodgkin's lymphomas

Table 5.11: Pediatric Hodgkin's lymphomas – 77 cases

Type	No.	%
Classic Hodgkin’s Lymphoma	66	85.70
Mixed cellularity	38	49.30
Nodular sclerosis	20	26.00
Lymphocyte rich	4	5.20
Lymphocyte depletion	4	5.20
Nodular lymphocyte predominance	5	6.50
Unspecified	6	7.80
Total	77	100.00

Figure 5.12: Percent type distribution of pediatric Hodgkin's lymphomas

Time trend changes in lympho-hematopoietic system, as seen in two Cancer Pathology Registries, showed reversed lymphoma:leukemia ratio and relative increase in NHL over HL (Table 5.12 and Figure 5.13).

Table 5.12: Time trend of lympho-hematopoietic system in

two Cancer Pathology Registries

Years	2003/2004	1985-1989
Male:female ratio	2.5:1	2.1:1
Lymphoma:leukemia ratio	0.84:1	1.8:1
NHL:HL ratio	3.3:1	2.3:1
% pediatric NHL	13.78	19.30
% pediatric HL	28.73	45.50
% Extranodal lymphoma	23.23	22.1

Figure 5.13: Time trend of lympho-hematopoietic system in two

Cancer Pathology Registries

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Chapter 6

Malignant Digestive System Tumors

The digestive system’s malignancies as a group ranked as the fourth most common after lympho-hematopoietic system, breast, and urinary system malignancies, constituting 13.45% of total malignancy with a slight male predominance of 54.62% and high adult predominance of 96.59%.

Table 6.1 and Figure 6.1 show that 6.58% of digestive system tumors are lymphomas. Table 6.2 and figure 6.2 show that colon, stomach, and rectum in that order of frequency constitute high figures. Relatively lower figures were seen in gall bladder and biliary tract, anal canal, pancreas, small intestine, and salivary glands, whereas, liver, and esophagus malignancies lie in between.

Table 6.1: Malignant tumors in digestive organs– 1413 cases

	No.	%
Digestive system tumors	1320	93.42
Lymphoid tumors in G.I.T.	93	6.58
Total	1413	100.00

Figure 6.1: Percent distribution of malignant tumors

in digestive organs– 1413 cases

Table 6.2: Digestive organ malignancies – 1413 cases

Site	No.	% Digestive	% Total
Colon	223	15.78	2.27
Stomach	208	14.72	2.12
Rectum	204	14.44	2.08
Liver	166	11.75	1.69
Oral cavity	154	10.90	1.57
Esophagus	141	9.98	1.43
Tongue	87	6.16	0.88
Small intestine	57	4.03	0.58
Salivary glands	48	3.40	0.49
Pancreas	41	2.90	0.42
Anal canal	39	2.76	0.40
Gall bladder and biliary tract	12	0.84	0.12
GIT NOS	33	2.34	0.34
Total	1413	100.00

Figure 6.2: Percent site distribution of digestive organ malignancies

Tongue and Oral Cavity

The tongue and oral cavity malignant tumors were 241 cases, constituting 17.06% of the malignancies of all digestive organs and 2.45% of total malignancy. The distribution of these tumors, as seen in table 6.3 and figure 6.3, revealed that the tongue was the most common site (36.10%).

Tongue and oral cavity malignant tumors were predominantly squamous carcinoma, while adenoid cystic carcinoma constituted 8 cases, malignant melanoma 3 cases, mucoepidermoid carcinoma 3 cases, non-Hodgkin’s lymphoma and malignant fibrous histiocytoma 2 cases each and neuroblastoma, malignant myoepithelioma, malignant salivary gland tumor and basal cell carcinoma one case each.

Table 6.3: Sites of malignant tongue and oral cavity tumors - 241 cases

Site	No.	% Oral	% Digestive	% Total
Tongue	87	36.10	6.16	0.88
Oral Cavity	154	63.90	10.90	1.57
Gum	46	19.09	3.26
Cheek	19	7.88	1.35
Hard palate	18	7.47	1.27
Lip	12	4.98	0.85
Retromolar area	12	4.98	0.85
Floor of mouth	3	1.24	0.21
Oral cavity NOS	44	18.26	3.11
Total	241	100.00	17.06	2.45

Tongue

Oral cavity

Figure 6.3: Percent site distribution of malignant tongue and oral cavity tumors

Salivary Glands

Salivary gland malignant tumors formed 3.40% of all digestive organ malignancies and 0.49% of total malignancy. Parotid gland, as seen in table 6.4 and figure 6.4, was the most common site, constituting 70.83% of salivary gland tumors.

Table 6.4: Sites of malignant salivary gland tumors – 48 cases

Site	No.	% Salivary tumors	% Digestive
Parotid	34	70.83	2.42
Salivary gland NOS	10	20.83	0.70
Submandiular	4	8.33	0.28
Total	48	100.00	3.40

Figure 6.4: Sites of malignant salivary gland tumors

Esophagus

Sites for esophageal tumors are seen in table 6.5 and figure 6.5. The lower third was occupied by almost one third of the cases 29.08%. Squamous carcinoma was 85% and adenocarcinoma 15%.

Table 6.5: Sites of malignant esophageal tumors – 141 cases.

Site	No.	%
Lower third	41	29.08
Middle third	18	12.77
Upper third	5	3.55
Esophagus NOS	77	54.60
Total	141	100.00

Figure 6.5: Percent distribution of malignant esophageal tumor sites

Stomach

Gastric tumors formed 2.12% of total malignancy. Histopathologic types and sites of malignant gastric tumors are seen in tables 6.6, 6.7 and corresponding figures. Adenocarcinoma was the most common type, although the site was not specified in more than three quarters of the pathology request form, the cardia was the most frequent site involved when stated.

Table 6.6: Histopathologic types of malignant gastric tumors –208 cases.

Type	No.	%
Glandular adenocarcinoma	99	47.60
Signet ring adenocarcinoma	43	20.66
Lymphoma	40	19.23
GIST	12	5.77
Undifferentiated carcinoma	6	2.88
Leiomyosarcoma	4	1.93
Unclassified tumors	4	1.93
Total	208	100.00

Figure 6.6: Histopathologic types of malignant gastric tumors (%)

Table 6.7: Sites of malignant gastric tumors – 208 cases.

Site	No.	%
Cardia	23	11.06
Pylorus	10	4.81
Lesser curvature	2	0.96
Fundus	1	0.48
Body	1	0.48
Greater curvature	1	0.48
Stomach NOS	170	81.73
Total	208	100.00

Figure 6.7: Percent site distribution of malignant gastric tumors

Colon

Histopathologic types and sites of malignant colonic tumors are seen in tables 6.8, 6.9 and corresponding figures. Adenocarcinoma was the most common type. Although the site was not precisely specified in about half of the reports (59%), the sigmoid colon was the most frequent site involved in colonic tumors, represented by 21.52%. Carcinoid malignant tumors were seen in two cases, one in sigmoid and one in colon NOS. One rare case of adenocarcinoid was seen in the colon.

Table 6.8: Histopathologic types of malignant colonic tumors- 223 cases

Type	No.	%
Glandular adenocarcinoma	146	65.47
Mucinous adenocarcinoma	48	21.52
Signet ring carcinoma	10	4.48
Lymphoma	8	3.60
GIST	4	1.80
Undifferentiated carcinoma	3	1.33
Malignant carcinoid	2	0.90
Carcinosarcoma	1	0.45
Adenocarcinoid	1	0.45
Total	223	100.00

Figure 6.8: Percent histopathologic types of malignant colonic tumors

Table 6.9: Sites of malignant colonic tumors- 223 cases

Site	No.	%
Sigmoid colon	48	21.63
Cecum	17	7.66
Recto-sigmoid	9	4.05
Splenic flexure	5	2.25
Transverse colon	4	1.80
Descending colon	3	1.35
Hepatic flexure	2	0.90
Ascending colon	2	0.90
Appendix	1	0.45
Colon NOS	132	59.01
Total	223	100.00

Figure 6.9: Percent site distribution of malignant colonic tumors

Ano-rectal

Ano-rectal malignant tumors formed 2.48% of total malignancy. Anal and rectal malignant tumors were mostly adenocarcinoma 87.85% as seen in table 6.10 and figure 6.10. The most frequent subtype was the glandular type, followed by mucinous and signet ring adenocarcinomas in descending order of frequency.

Table 6.10: Histopathologic types of malignant ano-rectal tumors-

243 cases

Type	No.	%
Glandular adenocarcinoma	140	57.61
Mucinous adenocarcinoma	61	25.10
Signet ring adenocarcinoma	12	4.94
Undifferentiated carcinoma	9	3.71
Malignant melanoma	5	2.06
GIST	5	2.06
Basaloid carcinoma	3	1.23
Squamous cell carcinoma	2	0.82
Lymphoma	2	0.82
Others	4	1.65
Total	243	100.00

Figure 6.10: Percent distribution of histopathologic types of

malignant ano-rectal tumors

Liver

Liver cancer formed 11.75% of the malignancies of all digestive organs and 1.68% of total malignancy. This registry shows under estimation of liver tumors because most of them are diagnosed by non-histopathology means. Liver tumors, as seen in figure 6.11, were mostly hepatocellular carcinoma 70.48%, while hepatoblastoma constituted 10.24%, non-Hodgkin's lymphoma 4.21% of hepatic malignancies and adenocarcinoma unspecified 9.03%.

Figure 6.11: Types of malignant liver tumors (%)

Gall Bladder and Extrahepatic Biliary System

Those malignant tumors accounted for 0.84% of digestive malignancies and 0.12% total malignancy. They were adenocarcinomas except only one case which was undifferentiated carcinoma. Data are shown in table 6.11 and figure 6.12.

Table 6.11: Histopathologic types of malignant gall bladder and

biliary tract tumors –12 cases

Type	No	%
Gall Bladder	10	83.33
Adenocarcinoma, NOS	6	50.00
Mucinous adenocarcinoma	2	16.67
Papillary adenocarcinoma	1	8.33
Undifferentiated carcinoma	1	8.33
Extrahepatic Biliary Tract Adenocarcinoma	2	16.67
Total	12	100.00

Figure 6.12: Percent distribution of histopathologic types of malignant gall bladder and biliary tract tumors

Pancreas

As regards the malignant pancreatic tumors, it constituted 2.9% of digestive malignancies and 0.42 of total malignancy. They were predominantly of the exocrine part, mostly adenocarcinoma of ductal origin, constituting (65.85%) of all cases. Special types of ductal adenocarcinoma such as mucinous adenocarcinoma, and signet ring adenocarcinoma were represented in 7.32% and 2.44% respectively (Table 6.12 and Figure 6.13).

Other carcinomas of exocrine part of pancreas like acinar cell carcinoma and undifferentiated carcinoma were minorities as shown in table 6.12.

Tumors of the endocrine part of pancreas so called malignant endocrine tumor, or endocrine carcinoma were far less than tumors of the exocrine part seen in only 9.76% of cases. This group includes malignant tumors arising from islet cells.

Tumors of indeterminate type or sometimes classified as mixed exocrine-endocrine type as solid cystic papillary epithelial tumors were represented in 7.32% of cases.

Table 6.12: Histopathologic types of malignant pancreatic tumors – 41 cases

Type	No.	%
Exocrine tumors	33	80.49
Adenocarcinoma	27	65.85
Mucinous adenocarcinoma	3	7.32
Signet ring adenocarcinoma	1	2.44
Acinar cell carcinoma	1	2.44
Undifferentiated carcinoma	1	2.44
Endocrine tumors	5	12.20
*Malignant endocrine tumor	4	9.76
Primitive neuroectodermal tumor	1	2.44
Mixed exocrine-endocrine tumors Solid cystic papillary epithelial tumor	3	7.32
Total	41	100.00

*Including islet cell carcinoma

Figure 6.13: Percent distribution of histopathologic types of malignant pancreatic tumors

Malignant Gastrointestinal Stromal Tumors (GIST)

A total of 36 cases of malignant GIST were diagnosed during the 2-year period of 2003-2004 representing 2.5% of digestive system malignancies and 0.36% of total malignant tumors. Soft tissue of the abdomen (mesentry and omentum) was the most common site followed by the stomach, the large intestine and then small intestine (Table 6.13 and Figure 6.14).

Table 6.13: Malignant gastrointestinal stromal tumors (GIST) - 36 cases

Site	No.	%
Mesentry & omentum	14	38.88
Stomach	12	33.33
Large intestine	9	25.00
Small intestine	1	2.79
Total	36	100.00

Figure 6.14: Malignant gastrointestinal stromal tumors (GIST) (%)

Lymphoma in Digestive System

A total of 93 cases of NHL were included, the stomach was the most common site for extra-nodal lymphoma in gastrointestinal tract (40 cases) followed by salivary glands (16 cases). Small intestine was involved in 13 cases; colon in 8 cases, oral cavity in 7 cases, liver in 7 cases and rectum in 2 cases (Table 6.14 and Figure 6.15).

Table 6.14: Distribution of lymphoma in digestive system - 93 cases

Site	No.	%
Stomach	40	43.00
Salivary gland	16	17.20
Small intestine	13	13.98
Colon	8	8.60
Oral cavity	7	7.53
Liver	7	7.53
Rectum	2	2.16
Total	93	100.00

Figure 6.15: Distribution of lymphoma in digestive system (%)

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Chapter 7

malignant Respiratory System tumors

Primary malignant tumors of the respiratory system were the fifth most common tumors (578 cases) in this registry material, constituting 5.90% of total malignancy, with high male predominance of 73% and high adult predominance 98.62%. With added lymphoma cases in respiratory system, the total number is 625 cases (Table 7.1 and Figure 7.1).

The relative frequency of the malignancies of respiratory organs as shown in table 7.2 and figure 7.2 demonstrates a relatively higher incidence of lung and laryngeal malignancies in relation to other malignancies of respiratory organs.

Table 7.1: Malignant tumors in respiratory organs– 625 cases

	No.	%
Respiratory system tumors	578	92.48
Lymphoid tumors	47	7.52
Total	625	100.00

Figure 7.1: Malignant tumors in respiratory system (%)

Table 7.2: Site distribution of malignant tumors

of respiratory system – 625 cases

Site	No.	% Respiratory	% Total
Larynx	174	27.84	1.77
Lungs	151	24.16	1.54
Hypopharynx	100	16.00	1.02
Pleura	82	13.12	0.84
Oropharynx	41	6.56	0.42
Nasopharynx	38	6.08	0.39
Nasal cavity and sinuses	35	5.60	0.36
Trachea	4	0.64	0.04
Total	625	100.00

Figure 7.2: Percent site distribution of malignant tumors

of respiratory system

Malignant tumors of the nasal cavity and sinuses constituted 5.6% of the malignancies of respiratory organs (35 cases) and 0.36% of total malignancy. The majority was in the maxillary sinus constituting 44.93%, tumors of ethmoid sinus were relatively rare. Table 7.3 and figure 7.3. show their distribution.

Soft tissue and bone tumors presented in the paranasal sinuses were not included with proper tumors of sinuses, but rather with the soft tissue and bone tumors respectively.

Table 7.3: Sites of malignant tumors of nasal cavity & sinuses – 35 cases

Site	No.	%
Nasal cavity	13	37.15
Maxillary sinus	17	48.57
Paranasal sinus	3	8.57
Ethmoid sinus	2	5.71
Total	35	100.00

Figure 7.3: Percent site distribution of malignant tumors

of nasal cavity and sinuses

Pharyngeal malignant tumors were divided into tumors of nasopharynx, oropharynx, and hypopharynx. The hypopharynx represented the most frequent site with 16% of respiratory malignancies. The sites of tumors were allocated in 52 out of the 100 tumors, the post cricoid region was the most frequent site 59.52%, followed by the pyriform sinus 21.73%, then posterior pharyngeal wall 18.75%. The histopathologic type was mainly squamous carcinoma, 95.03%.

Nasopharyngeal carcinomas were mostly of the undifferentiated type, 47.37%, non-Hodgkin’s lymphoma was 39.47%. Table 7.4 and figure 7.4 demonstrate these histopathologic types.

Table 7.4: Histopathologic types of nasopharyngeal malignant

tumors – 38 cases

Type	No.	%
Undifferentiated carcinoma	18	47.37
Lymphoma	15	39.47
Squamous carcinoma	3	7.90
Adenoid cystic carcinoma	1	2.63
Rhabdomyosarcoma	1	2.63
Total	38	100.00

Figure 7.4: Percent histopathologic types of nasopharyngeal tumors

Oropharynx: The most common site was the tonsil, being 58.54% of oropharyngeal tumors. The histopathologic types were predominantly non-Hodgkin’s lymphoma 65.85%. Tables 7.5., 7.6 and corresponding figures. demonstrate site distribution and histopathologic types of oropharyngeal tumors.

Table 7.5: Site distribution of malignant oropharnygeal tumors – 41 cases

Site	No.	%
Tonsil	24	58.54
Soft palate (uvula)	3	7.32
Oropharynx NOS	14	34.14
Total	41	100.00

Figure 7.5: Percent site distribution of malignant oropharnygeal tumors

Table 7.6: Histopathologic types of malignant oropharyngeal tumors – 41 cases

Type	No.	%
Non-Hodgkin’s lymphoma	27	65.85
Squamous carcinoma	8	19.51
Undifferentiated carcinoma	3	7.32
Mucoepidermoid carcinoma	2	4.88
Rhabdomyosarcoma	1	2.44
Total	41	100.00

Laryngeal malignant tumors constituted a major part of the malignancies of respiratory organs, 27.84%, and 1.77% of total malignancy. The site was allocated in only about a quarter of the cases, the supraglottic region was occupied in 15.52% (Table 7.7). The most common tumor type was squamous carcinoma; 95.96%.

Figure 7.6: Percent histopathologic types of oropharyngeal tumors

Table 7.7: Site distribution of malignant laryngeal tumors – 174 cases

Site	No.	%
Supraglottic	27	15.52
Vocal cord	8	4.59
Aryepiglottic fold	2	1.15
Anterior commissure	2	1.15
Larynx NOS	135	77.59
Total	174	100.00

Figure 7.7: Percent site distribution of malignant laryngeal tumors

Malignant tumors of the lower respiratory system including the lungs and bronchi constituted 24.16% of respiratory organ malignancies, and 1.54% of total malignancy. Their histopathologic types are shown in table 7.8 and figure 7.8.

Table 7.8: Histopathologic types of malignant lung tumors – 151 cases

Type	No.	%
Undifferentiated large cell carcinoma	45	29.80
Squamous cell carcinoma	33	21.85
Adenocarcinoma	32	21.20
Undifferentiated small cell carcinoma	23	15.23
Mucoepidermoid carcinoma	5	3.31
Sarcoma	4	2.65
Carcinoid	2	1.32
MALT	1	0.66
Desmoplastic round cell tumor	1	0.66
Carcinoma in situ	1	0.66
Combined undifferentiated and adenocarcinoma	1	0.66
Unclassified tumors	3	2.00
Total	151	100.00

Figure 7.8: Histopathologic types of malignant lung tumors

Malignant tumors of the pleura were all mesotheliomas (82 cases). They constituted 13.12% of respiratory system tumors and 0.84% of total malignancy. The ratio between malignant lung tumors and pleural mesothelioma was 1.8:1. Pleural mesothelioma showed a wide age range starting from the 3^rd to the 8^th decade. However the majority of the cases were between 30 to 70 years. The male to female ratio was 1.7:1. The percentage of different histologic subtypes of mesothelioma in pleura is shown in table 7.9 and figure 7.9. In small biopsy material, sometimes subtyping is not possible and the diagnosis of mesothelioma NOS is reported.

Table 7.9: Histopathologic subtypes of pleural mesothelioma- 82 cases

Type	No.	%
Epithelioid mesothelioma	37	45.13
Mesothelioma (NOS)	30	36.58
Biphasic mesothelioma	12	14.63
Sarcomatoid mesothelioma	3	3.66
Total	82	100.00

Figure 7.9: Percent of histopathologic subtypes of pleural mesothelioma

Lymphoma in Respiratory System

The sites of high incidence of lymphoma were the tonsils (20 cases), nasopharynx (15 cases), and oropharynx NOS and soft palate (7 cases). There was only one case of nasal NK/T cell lymphoma. MALT lymphoma was seen in one case of lung, trachea, and maxillary sinus, while one case of diffuse large NHL was seen in hypopharynx. No lymphoma cases were seen in the larynx (Table 7.10 and Figure 7.10).

Table 7.10: Lymphoma in respiratory system – 47 cases

Site	No.	%
Oropharynx	27	57.44
Tonsil	20	42.56
Soft palate	4	8.50
Oropharynx NOS	3	6.38
Nasopharynx	15	31.91
Hypopharynx	1	2.13
Nose	1	2.13
Trachea	1	2.13
Lung	1	2.13
Maxillary sinus	1	2.13
Total	47	100

Figure 7.10: Percent site distribution of lymphoma in respiratory system

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Chapter 8

malignant Female genital system tumors

Tumors of the female genital system represented 4.70% of total malignancy, with a high adult predominance of 97.61%. Only one lymphoid tumor was recorded (Table 8.1 and Figure 8.1). The relative frequency of the female genital tract malignancies, as seen in table 8.2 and figure 8.2, showed a high predominance of cervical tumors, 36.58% in contrast to lower figures of endometrial carcinomas 14.72%. Corpus uteri tumors including: endometrium, myometrium and uterine tumors NOS constituted 1.1% of total malignancies.

The histopathological tumor types of cervix as seen in table 8.3 and figure 8.3. showed a predominance of keratinizing squamous carcinoma being 39.64% of cervical malignancies while sarcoma constituted only 0.59% of cervical tumors. Cervical carcinoma in situ was very rare in this material; only one case of high grade squamous intraepithelial lesion was detected.

Table 8.1: Malignant tumors in Female Genital Organs– 462 cases

	No.	%
Female genital system tumors	461	99.78
Lymphoid tumors	1	0.22
Total	462	100.00

Figure 8.1: Malignant tumors in female genital organs (%)

Table 8.2: Relative frequency of female genital tract malignancies – 462 cases

Site	No.	% Female	% Total
Cervix	169	36.58	1.72
Ovary	135	29.22	1.37
Endometrium	68	14.72	0.69
Vulva	30	6.49	0.31
Vagina	20	4.33	0.20
Myometrium	5	1.08	0.05
Uterus NOS	35	7.58	0.36
Total	462	100.00	4.70

Figure 8.2: Percent site distribution of female genital tract malignancies

Table 8.3: Histopathologic types of malignant cervical tumors – 169 cases

Type	No.	%
Keratinizing squamous carcinoma	67	39.64
Large non-keratinizing squamous carcinoma	63	37.28
Small non-keratinizing squamous carcinoma	18	10.65
Adenocarcinoma	13	7.70
Clear cell carcinoma	2	1.18
Mixed Mullerian tumor	1	0.59
High grade squamous intraepithelial lesion	1	0.59
Undifferentiated tumor	3	1.78
Stromal sarcoma	1	0.59
Total	169	100.00

Figure 8.3: Percent histopathologic types of malignant cervical tumors

A total of 135 cases of ovarian malignant tumors represented 29.22% of female genital tract malignancies and 1.37% of total malignancy. Their histopathologic types are distributed in table 8.4 and figure 8.4.

The most common endometrial tumor was adenocarcinoma with the endometrioid subtype constituting three quarters of the cases. Sarcomas represented a minority of only 10.29% of total endometrial cancer. Their distribution is seen in table 8.5 and figure 8.5. The 5 cases of myometrial tumors were leiomyosarcoma.

Table 8.4: Histopathologic types of malignant ovarian tumors – 135 cases

Type	No.	%
Surface epithelial origin	99	73.33
Serous cystadenocarcinoma	47	34.82
Mucious cystadenocarcinoma	23	17.04
Adenocarcinoma	13	9.63
Undifferentiated carcinoma	7	5.18
Endometrioid adenocarcinoma	5	3.70
Papillary adenocarcinoma	2	1.48
Transitional carcinoma	1	0.74
Malignant Mixed Mullerian tumor	1	0.74
Sex cord-stromal origin	19	14.07
Granulosa cell tumor	16	11.85
Sarcoma	3	2.22
Germ cell origin	17	12.60
Teratoma	6	4.44
Dysgerminoma	4	2.97
Yolk sac tumor	4	2.97
Mixed germ cell tumor	3	2.22
Total	135	100.00

SEX CORD STROMAL ORIGIN 14.07%

GERM CELL ORIGIN 12.60%

SURFACE EPITHELIAL ORIGIN 73.33%

Figure 8.4: Histopathologic types of malignant ovarian tumors

Table 8.5: Histopathologic types of malignant endometrial tumors – 68 cases

Type	No.	%
Carcinoma	61	89.70
Endometroid adenocarcinoma	51	75.00
Squamous carcinoma	4	5.88
Papillary adenocarcinoma	3	4.41
Undifferentiated carcinoma	2	2.94
Adenoacanthoma	1	1.47
Carcinosarcoma	4	5.88
Endometrial stromal sarcoma	3	4.42
Total	68	100.00

Figure 8.5: Percent distribution of histopathologic types of endometrial tumors

Vulval and vaginal malignant tumors were mostly carcinomas, being 90% and 70% respectively. The histopathological types of vulval and vaginal malignant tumors are demonstrated in tables 8.6, 8.7 and corresponding figures respectively.

Table 8.6: Histopathologic types of malignant vulval tumors – 30 cases

Type	No.	%
Squamous carcinoma	27	90.01
Sarcomatoid carcinoma	1	3.33
Dermatofibrosarcoma	1	3.33
Non Hodgkin’s lymphoma	1	3.33
Total	30	100.00

Figure 8.6. Percent histopathologic types of malignant vulval tumors

Table 8.7: Histopathologic types of malignant vaginal tumors – 20 cases

Type	No.	%
Squamous carcinoma	10	50
Undifferentiated carcinoma	3	15
Adenosqumous carcinoma	1	5
Rhabdomyosarcoma	2	10
Malignant melanoma	1	5
Leiomyosarcoma	1	5
Carcinosarcoma	1	5
Mesenchymoma	1	5
Total	20	100

Figure 8.7: Percent distribution of histopathologic types

of malignant vaginal tumors

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Chapter 9

malignant Skin tumors

Malignant skin tumors constituted 3.74% of total malignancy. This group showed a high adult predominance of 95.08% and male predominance of 61.20%. Lymphomas formed 5.9% (Table 9.1 and Figure 9.1). With regard to the distribution in the body, tumors were predominantly in skin of the head (56.8%), distributed in descending order among skin of nose, scalp, lips, eyelids, forehead, cheek, ear, and lastly temple and chin (Table 9.2 and Figure 9.2).

Table 9.1: Malignant tumors in Skin– 389 cases

	No.	%
Skin tumors	366	94.10
Lymphoid tumors	23	5.90
Total	389	100.00

Figure 9.1: Percent distribution of malignant tumors in skin

Table 9.2: Site distribution of malignant skin tumors – 389 cases

Site	No	%
Head	221	56.80
Lower extremities	40	10.28
Upper extremities	14	3.60
Pelvis	13	3.34
Neck	8	2.06
Chest	8	2.06
Abdomen	5	1.29
Unspecified	80	20.57
Total	389	100.00

Figure 9.2: Percent site distribution of malignant skin tumors

* 20.57% unspecified site

More than half were presented to the Surgical Pathology Unit as surgical specimens. Carcinomas constituted nearly 90% of all primary skin malignancies. The relative frequency of the histopathologic types, as seen in table 9.3 and figure 9.3., demonstrates a high incidence of basal and squamous cell carcinomas, and a lower incidence of malignant melanoma and adnexal tumors. Non-Hodgkin’s lymphoma constituted nearly 6% of skin tumors, mostly of the mycosis fungoides type (85%).

Table 9.3. Histopathologic types of malignant skin tumors- 389 cases

Type	No.	%
Basal cell carcinoma	177	45.50
Squamous cell carcinoma	144	37.02
Non-Hodgkin's lymphoma	23	5.91
Malignant melanoma	20	5.14
Dermatofibrosarcoma	10	2.57
Kaposi's sarcoma	7	1.80
Sebaceous carcinoma	5	1.30
Verrucous carcinoma	2	0.51
Undifferentiated carcinoma	1	0.25
Total	389	100.00

Figure 9.3: Percent distribution of histopathologic types

of malignant skin tumors

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Chapter 10

Soft tissue sarcomas

Soft tissue sarcomas constituted 2.74% of total malignancy. This group of tumors showed a high percentage of pediatrics, 28.00%, and thus were number 3 in ranking of pediatric malignancies, after lympho-hematopoietic and bone tumors. Soft tissue sarcomas showed a male predominance of 60.07%.

The site distribution of soft tissue sarcomas as demonstrated in table 10.1 and figure 10.1 showed a higher predilection for the lower extremities and abdomen, constituting together 47.01% of cases. The most common site affected in the lower limbs was the thighs.

Table 10.1. Site distribution of soft tissue sarcomas – 268 cases

Site	No	%
Lower extremities	87	32.46
Abdomen	39	14.55
Chest	30	11.20
Pelvis	26	9.70
Upper extremities	20	7.46
Head	17	6.35
Neck	13	4.85
Unspecified	36	13.43
Total	268	100.00

Figure 10.1: Percent site distribution of soft tissue sarcomas

*13.43 % unspecified site

About half of the cases (51.10%) were presented to the Surgical Pathology Unit as surgical specimens. The relative frequency of the histopathologic types of soft tissue sarcomas is seen in table 10.2 and figure 10.2. Liposarcoma (mostly of the myxoid type) was the most common soft tissue sarcoma. This was followed by rhabdomyosarcoma and primitive neuroectodermal tumor, showing almost equal proportions. Rare sarcomas like extraskeletal osteosarcoma and chondrosarcoma, epithelioid sarcoma, desmoplastic small round cell tumor and mesenchymoma formed collectively 3.73% of cases. There was a relatively high frequency of undifferentiated sarcomas, forming 14.93% of cases.

Table 10.2: Histopathologic types of soft tissue sarcomas - 268 cases

Type	NO.	%
Liposarcoma	43	16.04
Rhabdomyosarcoma	37	13.80
Primitive neuroectodermal tumor	35	13.06
Malignant fibrous histiocytoma	27	10.07
Synovial sarcoma	26	9.70
Malignant peripheral nerve sheath tumor	19	7.09
Fibrosarcoma	12	4.48
Leiomyosarcoma	9	3.36
Alveolar soft part sarcoma	5	1.87
Vascular sarcomas	5	1.87
Rare sarcomas	10	3.73
Undifferentiated sarcoma	40	14.93
Total	268	100.00

Figure 10.2: Histopathologic types of soft tissue sarcomas

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Chapter 11

malignant Bone tumors

Malignant bone tumors constituted 1.92% of total malignancy. This group of tumors showed a high percentage of pediatrics, 54.80%, and thus were number 2 in ranking of pediatric malignancies, after lympho-haematopoietic malignancies. Bone tumors showed a male predominance of 63.83%. Lymphoma and myeloma represented in bones were 15.3% (Table 11.1 and Figure 11.1)

The site distribution of malignant bone tumors as demonstrated in table 11.2 and figure 11.2. showed a high percentage in the lower extremities, constituting half of the cases, 50.45%. The most common sites in the lower limbs in descending order were the femur, tibia, and lastly fibula.

Table 11.1: Malignant tumors in Bone– 222 cases

	No.	%
Bone tumors	188	84.68
Lymphoma and Myeloma	34	15.32
Total	222	100.00

Figure 11.1: Malignant tumors in Bone– 222 cases (%)

Table 11.2: Site distribution of malignant bone tumors – 222 cases

Site	No	%
Lower extremities	112	50.45
Upper extremities	23	10.36
Pelvis	22	9.91
Skull	17	7.66
Vertebral column	13	5.86
Thorax	6	2.70
Unspecified	29	13.06
Total	222	100.00

Figure 11.2: Percent site distribution of malignant bone tumors

* 13.06% unspecified site

About 1/4 of the cases were presented to the Surgical Pathology Unit as surgical specimens. Osteosarcoma was the most common primary malignant bone tumor, forming 47.75%, followed by Ewing's sarcoma (17.57%), while chondrosarcoma came third (14.86%) and NHL came fourth (9.01%). The relative frequency of the histopathologic types of malignant bone tumors is seen in table 11.3 and figure 11.3.

Table 11.3: Histopathologic types of malignant bone tumors – 222 cases

Type	No.	%
Osteosarcoma	106	47.75
Ewing's sarcoma	39	17.57
Chondrosarcoma	33	14.86
Non-Hodgkin's lymphoma	20	9.01
Plasma cell myeloma	14	6.31
Other sarcomas	6	2.70
Chordoma	2	0.90
Langerhan's cell histiocytosis	2	0.90
Total	222	100.00

Figure 11.3: Percent distribution of histopathologic types

of malignant bone tumors

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Chapter 12

Malignant Endocrine system tumors

This group constituted a minority of 2.23% of total malignancies with an adult predominance of 66.66%. The sex distribution showed no outstanding predilection, females constituting 53.42%. Lymphomas formed a minority of 1.3% (Table 12.1 and Figure 12.1).

A total of 222 cases were included in this group of endocrine gland tumors. Malignant thyroid gland tumors as seen in table 12.2 and figure 12.2. constituted a majority of 65.31% of endocrine malignant tumors, the rest were adrenal gland malignant tumors forming 19.37% and extra-adrenal neuroblastoma forming 15.32%. There were no documented cases of malignant parathyroid or pituitary gland tumors during the 2 years of this registry. The rarity of pituitary gland tumors in particular, could be due to the fact that neurosurgery is not within the domain of NCI, thus the incidence of these tumors might be underestimated.

Table 12.1: Malignant tumors in endocrine glands– 222 cases

Type	No.	%
Endocrine system tumors	219	98.65
Lymphomas	3	1.35
Total	222	100.00

Figure 12.1: Percent malignant tumors in endocrine glands

Table 12.2: Malignant endocrine tumors- 222 cases

	Site	No.	%	% Total
	Thyroid gland	145	65.31	1.48
	Adrenal gland	43	19.37	0.44
	Extra-adrenal sites	34	15.32	0.35
	Total	222	100.00

Figure 12.2: Malignant endocrine tumors (%)

The M/F ratio of thyroid gland tumors was 1:1.6 showing female predominance. While M/F ratio of adrenal gland tumors was 2.8:1. Also age distribution between tumors of these two glands showed marked difference, with predominance of adult cases in thyroid tumors (97.95%), as opposed to few cases in adrenal tumors (15.56%).

The most common malignant tumor of thyroid gland was papillary carcinoma (Table 12.3 and Figure 12.3). The most common malignant adrenal gland tumor was neuroblastoma, 36 cases. (Table 12.4 and Figure 12.4).

Table 12.3: Histopathologic types of malignant thyroid tumors – 145 cases

Type	No.	%
Papillary carcinoma	98	67.59
Follicular carcinoma	25	17.24
Medullary carcinoma	10	6.90
Anaplastic carcinoma	9	6.20
Non-Hodgkin's lymphoma	3	2.07
Total	145	100.00

Figure 12.3: Percent distribution of histopathologic types

of malignant thyroid tumors

Table 12.4: Histopathologic types of malignant tumors of adrenal gland and extra-adrenal ganglia - 77 cases

Type	No.	%
Adrenal gland neuroblastoma	36	46.75
Extra-adrenal neuroblastoma	34	44.15
Adrenal cortical carcinoma	3	3.90
Unclassified	4	5.20
Total	77	100.00

Figure 12.4: Percent distribution of histopathologic types

of malignant adrenal tumors

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Chapter 13

malignant Male genital system tumors

Malignant male genital tumors constituted only 0.97% of total malignancy, with a high adult predominance of 94.74%. The relative frequency of male genital malignancies is shown in table 13.1 and figure 13.1. Prostatic tumors showed a higher frequency than testicular tumors. They were almost all adenocarcinomas as seen in table 13.2 and figure 13.2. The relative frequency of histopathologic types of testicular tumors - as seen in table 13.3 and figure 13.3 - shows high figures of seminoma (56.4%).

Table 13.1: Relative frequency of male genital tract malignancies – 95 cases

Site	No.	% Male	% Total
Prostate	47	49.48	0.48
Testis	39	41.05	0.40
Extra-gonadal	7	7.37	0.07
Penis	1	1.05	0.01
Scrotum	1	1.05	0.01
Total	95	100.00	0.97

Figure 13.1: Percent distribution of male genital tract malignancies

Table 13.2: Histopathologic types of malignant prostatic tumors – 47 cases

Type	No.	%
Adenocarcinoma	45	95.74
PIN	1	2.13
Undifferentiated small cell carcinoma	1	2.13
Total	47	100.00

Figure 13.2: Percent distribution of histopathologic types

of malignant prostatic tumors

Table 13.3: Histopathologic types of malignant testicular tumors – 39 cases

Type	No.	%
Seminoma	22	56.40
Mixed germ cell tumor	4	10.26
Yolk sac tumor	4	10.26
Embryonal carcinoma	3	7.70
Malignant teratoma	3	7.70
Undifferentiated carcinoma	1	2.56
Fibrosarcoma	1	2.56
Leiomyosarcoma	1	2.56
Total	39	100.00

Figure 13.3: Percent distribution of histopathologic types

of malignant testicular tumors

The extra-gonadal malignant tumors were located mostly in soft tissue of pelvis except for two cases that were located in soft tissue of mediastinum. These cases were as follows: teratoma 3 cases, yolk sac tumor 2 cases, and two cases of seminoma. Penile and scrotal tumors (2 cases) were squamous carcinoma.

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Chapter 14

malignant Central nervous system tumors

This group constituted only 0.77% of total malignancy with a slight adult predominance of 54.44% and no sex predilection (50% each). The low number of such tumors could be attributed to the lack of neurosurgery practice at NCI. All except two cases were in the brain, those were located in the spinal cord. Astrocytoma was the most common tumor, 51 cases constituting 67.10% of total CNS tumors and 0.52% total malignancy, the majority were classified as fibrillary astrocytomas (WHO grade II). Table 14.1 and figure 14.1 represent their distribution.

Table 14.1 Central nervous system malignancies – 76 cases

Type	No.	%
Astrocytoma	51	67.10
Fibrillary (WHO grade II)	27	35.52
Anaplastic (WHO grade III)	12	15.79
Glioblastoma multiforme (WHO grade IV)	9	11.84
Pilocytic (WHO grade I)	3	3.95
Medulloblastoma	10	13.15
Ependymoma	7	9.21
Central PNET	4	5.26
Pleomorphic xanthoastrocytoma	1	1.32
Choroid plexus carcinoma	1	1.32
Cerebellar hemangioblastoma	1	1.32
Malignant meningioma	1	1.32
Total	76	100.00

Figure 14.1 Percent distribution of central nervous system malignancies

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Chapter 15

malignant Eye and ear tumors

This group included proper tumors of eyes and ears, and constituted a minority of 0.16% of total malignancy. They showed adult predominance of 75% and no sex predilection (50% each). Tumors of skin and soft tissue of eye and ears were considered with the skin and soft tissue tumors respectively. Only 14 cases of malignant eye tumors were included, 6 of which were in the conjunctiva where the majority were squamous carcinoma (5 cases) and the sixth was undifferentiated carcinoma. Malignant melanoma and retinoblastoma were represented by four cases each (Table 15.1 and Figure 15.1). Only two cases of squamous carcinoma from middle ear were included.

Table 15.1: Histopathologic types of malignant eye tumors - 14 cases

Type	No.	%
Squamous carcinoma	5	35.71
Retinoblastoma	4	28.57
Malignant melanoma	4	28.57
Undifferentiated carcinoma	1	7.15
Total	14	100.00

Figure 15.1: Percent distribution of histopathologic types

of malignant eye tumors

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Chapter 16

Multiple malignant tumors

This group included multiple tumors within the same organ or different anatomic sites. Table 16.1 and figure 16.1 show the characteristic sites of multiple malignant tumors. The breast was the most common site, and duct carcinoma was the most common histopathologic type (Table 16.2 and Figure 16.2).

Table 16.1: Sites of multiple tumors – 183 cases

Site	No.	%
Breast	70	38.25
Bladder	35	19.12
Ovary	18	9.84
Skin	15	8.20
Colorectal	13	7.10
Thyroid	9	4.92
Others	23	12.57
Total	183	100.00

Figure 16.1: Percent distribution of sites of multiple tumors

Table 16.2: Histopathologic types of multiple tumors - 183 cases

Type	No.	%
Duct carcinoma	57	31.15
Adenocarcinoma	37	20.22
Transitional cell carcinoma	26	14.21
Squamous cell carcinoma	16	8.74
Basal cell carcinoma	10	5.46
Lobular carcinoma	5	2.73
Others	32	17.49
Total	183	100.00

Figure 16.2: Percent distribution of histopathologic types of multiple tumors

Multiple malignant tumors in different anatomic sites:

Six cases were encountered in this rare group. Their details are presented in table 16.3.

Table 16.3: Multiple malignant tumors in different anatomic sites- 6 cases.

No.	Diagnosis and site of presentation
2	Laryngeal squamous carcinoma and papillary thyroid carcinoma
1	Cervical squamous carcinoma and endometrial adenocarcinoma
1	Cervical squamous carcinoma and anal canal melanoma
1	Cervical squamous carcinoma and bladder transitional cell carcinoma
1	Endometrial adenocarcinoma and malignant rectal polyp

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Chapter 17

Locally recurrent tumors

This group included tumors that recurred locally either within the 2 years of the study or only the recurrence was included. Table 17.1 and figure 17.1 show that soft tissue compartment, skin, and urinary bladder were the most common sites of local recurrence of malignant tumors. This group of 522 cases was not included with primary malignant tumors.

Table 17.1: Sites of locally recurrent malignant tumors – 522 cases

Site	No.	%
Soft tissue	180	34.48
Skin	96	18.39
Urinary bladder	43	8.24
Oral cavity	32	6.13
Colon and rectum	28	5.36
Breast	26	4.98
Paranasal sinuses	17	3.26
Vagina	12	2.30
Bone	11	2.10
Cervix	10	1.92
Larynx	10	1.92
Stomach	8	1.53
Nasopharynx and oropharynx	6	1.15
Thyroid gland	5	0.96
Urethra	5	0.96
Others	33	6.32
Total	522	100.00

Figure 17.1: Sites of locally recurrent malignant tumors

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Chapter 18

metastatic TUMOrs at initial presentation

WITH unknown primary

These tumors were initially seen as metastases. A total of 557 cases included showed that lymph nodes were the most common site for such presentation, constituting about half of cases (45.96%). In about third of these cases the histopathologic type was undifferentiated carcinomas thus the primary tumor could not be specified. In other cases the diagnosis was adenocarcinoma, squamous carcinoma, duct carcinoma, transitional carcinoma or neuroblastoma thus suggesting the location of the primary tumor. The different sites and histopathologic types are seen in tables 18.1 and 18.2 and corresponding figures respectively.

Table 18.1: Sites of metastasis of tumors at initial presentation – 557 cases

Site	No.	%
Lymph nodes	256	45.96
Soft tissues	124	22.26
Bone	46	8.26
Liver	34	6.10
Pleura	15	2.69
Peritoneum	17	3.05
Lung	7	1.26
Bone marrow	9	1.62
Ovary	8	1.44
Others	41	7.36
Total	557	100.00

Figure 18.1: Percent site distribution of metastatic

tumors at initial presentation

Table 18.2: Histopathologic types of tumors metastatic

at initial presentation – 557 cases

Type	No.	%
Adenocarcinoma	205	36.80
Undifferentiated carcinoma	178	31.96
Squamous carcinoma	36	6.46
Duct carcinoma	31	5.56
Signet ring carcinoma	18	3.23
Transitional carcinoma	15	2.70
Neuroblastoma	13	2.34
Others	61	10.95
Total	557	100.00

Figure 18.2: Histopathologic types of tumors metastatic at initial presentation

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Chapter 19

Metastatic recurring tumor

This group includes tumors recurring distant from their primary site. Tables 19.1, 19.2 and corresponding figures demonstrate the site of recurrences and their histopathologic types. The lymph nodes were the most common site for metastatic recurrent tumors, and adenocarcinoma was the most common histopathologic subtype. This group was not included with the primary malignant tumors.

Relapsing lymphomas diagnosed by histopathology (14 cases) were not included in the group of locally or metastatic recurrent tumors, but with lymphoid tumors. This separate group formed eight cases of non-Hodgkin's lymphomas and six cases of Hodgkin's lymphomas.

Table 19.1: Sites of metastatic recurrent tumors – 249 cases

Site	No.	%
Lymph nodes	82	32.93
Soft tissue	70	28.11
Lung	34	13.65
Skin	18	7.23
Bone	17	6.83
Liver	11	4.42
Rest	17	6.83
Total	249	100.00

Figure 19.1: Percent site distribution of metastatic recurrent tumors

Table 19.2: Histopathologic types of metastatic recurrent tumors – 249 cases

Type	No.	%
Adenocarcinoma	79	31.73
Sarcomas unspecified	42	16.87
Squamous cell carcinoma	41	16.47
Undifferentiated carcinoma	19	7.63
Duct carcinoma	16	6.43
Neuroblastoma	15	6.02
Transitional cell carcinoma	7	2.81
Melanoma	7	2.81
Germ cell tumors	4	1.60
Others	19	7.63
Total	249	100.00

Figures 19.2: Histopathologic types of metastatic recurrent tumors

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Chapter 20

Tumors of border-line malignancy

Tumors of border-line malignancy, recently termed tumors of low malignant potential, included 218 cases. Table 20.1 and figure 20.1 show their histopathologic types. The most common types include fibromatosis, giant cell tumor of bone, and epithelial ovarian tumors of borderline malignancy. This group was not included with the primary malignant tumors.

Table 20.1: Histopathologic types of tumors

of borderline malignancy – 218 cases

Type	No.	%
Fibromatosis	88	40.37
Giant cell tumor	40	18.35
Epithelial ovarian tumors	16	7.34
Ameloblastoma	11	5.05
Verrucous neoplasm	9	4.13
Phyllodes tumor	8	3.67
Myxoma	8	3.67
Hemangioendothelioma	6	2.75
Carcinoid tumor	4	1.83
Inflammatory myofibroblastic tumor	4	1.83
Papillary transitional neoplasm	3	1.38
Desmoplastic fibroma	3	1.38
Others	18	8.25
Total	218	100.00

Figure 20.1: Histopathologic types of tumors of borderline malignancy