HISTOPATHOLOGY PATTERNS OF MALIGNANT SOFT TISSUE TUMORS: IN JIMMA UNIVERSITY MEDICAL CENTER: 5 YEARS RETROSPECTIVE STUDYBY MEBRAT NIGUSE (MD)A RESEARCH PROPOSAL TO BE SUBMITTED TO DEPARTMENT OF PATHOLOGY FACULTY OF MEDICAL SCIENCES, JIMMA UNIVERSITY INSTITUTE OF HEALTH IN PARTIAL FULFILLMENT OF THE REQUIREMENT FOR THE SPECIALITY IN HUMAN PATHOLOGY.JUNE, 2018JIMMA ETHIOPIAJIMMA UNIVERSITYFACULTY OF MEDICAL SCIENCESDEPARTMENT OF PATHOLOGY HISTOPATHOLOGY PATTERNS OF MALIGNANT SOFT TISSUE TUMORS: IN JIMMA UNIVERSITY MEDICAL CENTER: 5 YEARS RETROSPECTIVE STUDY BY: MEBRAT NIGUSE (MD)ADVISORS:1. DR MESELE BEZABIH (ASSOCIATE PROF. OF PATHOLOGY, EPIDEMIOLOGIST )2. MRS.
TAMIRAT Abstract Background: Soft tissue is defined as the complex of nonepithelial extra skeletal structures of the body exclusive of the supportive tissue of the various organs and the hematopoietic/lymphoid tissue. It accounts for a substantial portion of the body but tumors are relatively rare, and are diagnostically challenging as they comprise a large spectrum of diagnostic entities.Objective: To describe the histopathology patterns of malignant soft tissue tumors in Jimma University Medical Center, 2010Methods: Retrospective Descriptive cross sectional study design will be conducted based on records of patients in pathology department during September 1, 2004 to August 30, 2009 E.C. from august 01/12/2010 to 30/12/2010. Records of all soft tissue tumor biopsy of patients sent to JUMC, Pathology department will be reviewed and all malignant soft tissue tumor biopsy of patients during the five years which fulfills the inclusion criteria will be identified and entered into Epi data v.3.1 and exported to SPSS V.
20 for analysis. Finally result will be presented using tables, graphs or in narrative formWork plan and budget. The plan of this study is from May 2010 to December 2011 E.
CKey words: histopathology patterns, grades of tumor.Acknowledgement I would like to express my deepest gratitude to Jimma university for providing me this opportunity and my advisors who gave me insights and valuable information and initiating me from topic selection to writing and preparing this paper.Table of contentsContentsAbstract 3Acknowledgement 4Table of contents 5List of tables and figures 7Acronyms and abbreviations 8Introduction 9Statement of the problem 10Literature review 12Significance of the study 16Objectives 17General objectives 17Specific objectives 17Methods and materials 18Study area and study period 18Study design 18Population 18Source population 18Study population 18Sample size 18Sampling techniques 18Inclusion and Exclusion criteria 19Inclusion criteria 19Exclusion criteria 19Data collection techniques 19Data quality assurance 19Variables 19Data analysis 19Ethical consideration 21WORK PLAN 22Budget break down 23Dummy tables 24References 27Check list format 29List of tables and figures Table 1: Frequency distribution of patients by sexTable 2: Frequency distribution of patients by ageTable 3: Frequency distribution of patients by addressTable 4: Frequency of tumors distribution by type of tumorTable 5: Frequency of tumor by sites or locationTable 6: Frequency distribution of tumor by gradesTable 7: Frequency distribution of tumor by histological patternsAcronyms and abbreviations JUMC- Jimma University Medical ScienceSTT- Soft Tissue TumorSTS- Soft Tissue SarcomaNOS-Not Otherwise SpecifiedWHO- World Health Organization MFH- Malignant Fibrous HistocytomaRMS- RhabdomyosarcomaDFSP-Dermato Fibro sarcoma Protuberance Introduction Soft tissue is defined as the complex of nonepithelial extra skeletal structures of the body exclusive of the supportive tissue of the various organs and the hematopoietic/lymphoid tissue. It is composed of fibrous (connective) tissue, adipose tissue, skeletal muscle, blood and lymph vessels, and peripheral nervous system (1). Soft tissue sarcomas are the most common subset of tumors that arise from the embryonic mesoderm. The term sarcoma is derived from the Greek sarcoma meaning ‘fleshy growth’ and sarcomas can occur anywhere in the body and are diagnostically challenging as they comprise a large spectrum of diagnostic entities.
For every soft-tissue sarcoma diagnosed, there are over 100 benign soft-tissue tumors (2).There is a huge variability in histopathological subtypes of soft tissue sarcoma. Generally classification of soft tissue sarcoma is centered upon particular cellular lineages on the basis of morphology and immunohistochemical profiles. However, in a substantial number of cases no such cellular lineage is apparent and classification relies on morphological criteria There are certain histological subtypes of soft tissue sarcoma that have distinct biological behaviors that influence management, the most important example being tumors displaying intrinsic chemo sensitivity. Ewing’s sarcoma and pediatric embryonal rhabdomyosarcoma are exquisitely chemo sensitive, and synovial sarcoma which usually presents in young adults is relatively chemo sensitive. For these subtypes induction chemotherapy prior to surgery is often indicated (3).Tumors arising in soft tissue, although clinically often no distinctive, form a varied and complex group that may show a wide range of differentiation. To an extent perhaps shared only by hematolymphoid disorders, the morphology of soft tissue lesions frequently belies their true biologic potential: Examples of pseudo malignancy and even pseudo benignity abound.
For this reason alone, in the absence of a firm histological diagnosis it is often dangerous to attempt to predict (or “guess at”) the likely clinical course of a given soft tissue neoplasm (4). Statement of the problem Tumors of soft tissue are among the most challenging in surgical pathology. There are several reasons for this: they are rare, so you see few in training; they are overlapping in morphology; they do not always obey the principles that help you to identify malignant potential in carcinomas; and each entity has at least three names, four variants, and many mimickers. According to American cancer society report the most common types of sarcoma in adults are: Undifferentiated pleomorphic sarcoma (previously called malignant fibrous histiocytoma), Liposarcoma, Leiomyosarcoma. (5).Etiology of most benign and malignant soft tissue tumor is unknown.
In rare cases genetics, and environmental factors; viral infections, immunodeficiency states, chemicals, irradiation have been found to be associated with the development of usual soft tissue malignancies. There are also isolated reports of sarcoma arising from scar tissue sites, fractures sites and close to surgical implants. Some angiosarcoma also arise from lymph edema.
However most sarcomas arise denovo (6). Tumors of the musculoskeletal system are an extremely heterogeneous group of neoplasms consisting of greater than 200 benign types of neoplasms and approximately 90 malignant conditions. Malignant tumors or sarcomas are capable of invasive, locally destructive growth with a tendency to recur and to metastasize. Soft tissue and bone sarcomas have an annual incidence in the United States of more than 6000 and 3000 new cases, respectively. When compared with the overall average cancer mortality of 550,000 cases per year, sarcomas are a small fraction of the problem. However, although a relatively uncommon form of cancer, these mesenchymal tumors behave in an aggressive fashion with reported current mortality rates in some series greater than 50%. Sarcomas are more common in older patients, with 15% affecting patients younger than 15 years and 40% affecting persons older than 55 years. Accordingly, as the population ages, as it is doing at a rapid rate, the incidence of these tumors will increase (7).
Malignant soft tissue tumors ultimately come to medical attention. Soft tissue sarcomas, compared with carcinomas and other neoplasms, are relatively rare and constitute less than 1.5% of all cancers with an annual incidence of about 6 per 100,000 persons.
However, according to an analysis of the Surveillance, Epidemiology and End Results (SEER) database, the incidence changes with age ; for children younger than 10 years of age, the annual incidence was 0.9/100,000 children but rose to 18.2/100,000 adults over the age of 70 years. The most dramatic increases occurred at 30 and 70 years of age. Judging from the available data, the incidence and distribution of soft tissue sarcomas seem to be similar in different regions of the world.
Soft tissue sarcomas may occur anywhere in the body, but most arise from the large muscles of the extremities, the chest wall, the mediastinum, and the retro peritoneum. They occur at any age and, like carcinomas, are more common in older patients. Soft tissue sarcomas occur more commonly in males, but gender and age-related incidences vary among the histological types: for instance, embryonal rhabdomyosarcoma occurs almost exclusively in young individuals, whereas undifferentiated pleomorphic sarcoma is predominantly a tumor of old age and is rare in children younger than 10 years (8). There is limited studies in Africa about soft tissue tumors and only a single soft tissue cytopathology was accessed in Ethiopia by the researcher; therefore in absence of well established cancer registry system, and studies such record analysis provide useful information for understanding the changing trend and pattern and help in undertaking further studies in identifying the associated factors is immense importance for developing appropriate strategies and prioritizing control measures. This study is intended to describe the histopathology patterns of soft tissue tumors and hope it will fill the existing gapLiterature review Soft tissue tumours may arise in any location, 40% occur in the lower extremities the thigh, 20% in the upper extremities, 10% in the head and neck and 30% in the trunk and retro peritoneum. Malignant soft tissue tumors are seen more commonly in males than in females in the ratio 1.4:1 and incidence increases with the increasing age.
At least one third of the benign tumors are lipomas, another one third is fibrohistiocytic and fibrous tumors, 10% are vascular tumors and 5% nerve sheath tumors. Of the benign soft tissue tumors 99% are superficial and 95% are less than 5 cm in diameter. (1, 2)According study done in USA, Leiomyosarcoma was the most common sarcoma, accounting for 23.
9% of cases (incidence rate 1.23). Other major histological types included malignant fibrous histiocytoma (MFH) 17.1%, liposarcoma 11.
5%, dermatofibrosarcoma 10.5% and rhabdomyosarcoma 4.6. The higher rates for both uterine leiomyosarcoma and dermatofibrosarcoma among blacks were apparent at virtually all ages. Rates for both uterine leiomyosarcoma and dermatofibrosarcoma rose rapidly during the childbearing years and peaked about age 40 and 50 years, respectively, before declining thereafter. Rates for the group of other specified sarcomas did not change with age. Age-specific rates for all rhabdomyosarcomas combined were bimodal, with rates elevated in childhood and at older ages. The peak in childhood was due primarily to rates for embryonal rhabdomyosarcoma, which were highest at birth and during childhood, before declining rapidly through adolescence and early adulthood until about age 40 years.
The highest rates for alveolar rhabdomyosarcoma occurred in childhood and adolescence before decreasing until about 20 years of age. In contrast, rates for pleomorphic rhabdomyosarcoma generally increased with age (9). A 25 years retrospective study done in Serbia shows 1308 STS patients were registered, the most frequent histological type was NOS sarcoma , (i.
e., at that moment, not included in the existing, precisely defined classifications) which developed in every fourth patient (27%). It was followed by leiomyosarcoma (21%), liposarcoma (14%), rhabdomyosarcoma (11%) and malignant fibrous histiocytoma, 248 (19%). cases, occurs at the age younger than 39, STS mostly occurs at the older age. The highest age-specific rates occur in two moderate peaks, the first one between 55-59 (5.
31/100 000), and the second one between 70-74 (5.32/100 000 (10). According to journal from India Mangaluru, Karnataka, a total of 35 cases of malignant soft tissue sarcomas were studied and Malignant Fibrous Histiocytoma and Liposarcoma were the commonest tumors consisting 7 (20%) each out of 35 cases. The least common were Clear Cell Sarcoma, Leiomyosarcoma, Synovial Sarcoma, Malignant Hemangiopericytoma, Alveolar Soft Part Sarcoma and Extra skeletal Osteosarcoma (One case each) Most of the cases were seen in the age group of 51 -60 years.
The lowest age in which tumors found was a 25 day old baby girl who was diagnosed of Infantile Fibro sarcoma. The oldest individual was a 70 year old man who was diagnosed to have Malignant Fibrous Histiocytoma. Males had higher incidence of tumors than females. Among the various sites, lower extremity was the commonest site 18(51.42%), followed by the upper extremity 9(25.71%) and posterior chest wall 4(11.
42%). The head and neck region were relatively rare sites 1(2.8%) and 2(5.7%) retroperitoneal (11).A two year retrospective study done in Syria from a total of 308 patients, with a musculoskeletal tumor were evaluated malignant tumors consisted of seven diagnostic categories: malignant fibrous histiocytoma (23%), liposarcoma (22%), rhabdomyosarcoma (9%), leiomyosarcoma (8%), malignant schwannoma (5%), dermatofibrosarcoma protuberant (5%), synovial sarcoma (10%), fibro sarcoma (13%), extra skeletal chondrosarcoma (1%), and extra skeletal Ewing sarcoma (4%) (12).
Another study, done in India on 200 soft tissue tumors, out of which 169 (84.5%) cases were benign, 11 (5.5%) were intermediate and 20 (10.
0%) malignant tumors. The age ranged from 6 months to 98 years. Benign tumors were found to be more common in younger population whereas malignant tumors were commoner in 5th to 6th decade of life.
The male to female ratio was 1.1:1. The most common benign tumors were lipoma (44.5%) followed by hemangioma (14.0%) and schwannoma (5.5%). The commonest malignant tumors were sarcomas NOS (n=10; 5.
0%) followed by leiomyosarcoma. (n=4; 2.0%).
The benign tumors were found to be commoner in younger population whereas malignant tumors were seen in 5th to 6th decade. Statistically highly significant correlation was found between age and the category of tumor (p value = 0.004). Although rhabdomyosarcomas are malignant tumors but they were seen in 2nd decade of life.
The most common site of soft tissue tumors as a whole was head ; neck (29.0%) followed by upper limb (25.5%). Among benign tumors, hemangiomas had a predilection for head ; neck (10.5%) while lipomas were seen commonly in upper limb (14.5%).Most favored site for sarcomas was lower limb (n=10; 5.0%), out of which 5 cases were of sarcomas NOS.
The second most common site involved by sarcomas was abdomen (n=5; 2.5%) (13).A four year retrospective study done in Pakistan from 26 cases, age range was from 1 to 75 years with mean age of 30.68 ±17.71 years. Male to female ratio is1.
13:1. Benign tumors were 176(65.91%) cases, and malignant were 91 (34.08%) cases. Amongst benign tumors haemangiomas were 73 (27.3%) followed by lipoma 41 (15.
35%) cases, benign fibrous histiocytoma (BFH) 23 (8.6%) cases and Schwannoma 14 (5.2%) cases. Among the malignant tumors 35 (13.1%) cases were of rhabdomyosarcoma followed by angiosarcoma 14 (5.
2%) cases , malignant fibrous histiocytoma (MFH) 12 (4.5%) cases and fibro sarcoma and malignant peripheral nerve sheath tumors (MPNST) 6 (2.2%) and 5 (1.9%) cases respectively (14).
Study done in Nigeria on patterns of sarcoma and A total of 264 cases of soft tissue sarcomas were reviewed; 162 males and 102 females with a male to female ratio of 1.6:1. The age range was between 3 months and 89 years with a mean age of 39.0 years. Kaposi sarcoma was the predominant histological type with 56 cases (21.2%). Then rhabdomyosarcoma with 54 (20.
5%) cases, dermatofibrosarcoma with 52 (19.7%) cases and liposarcoma with 32 (12.0%) cases.
The most common site of affectation was the lower limb with 73 (27.7%) cases, followed by the trunk with 66 (25.0%) cases, head and neck with 45 (17.0%) cases and upper limb with 35 (13.3%) cases.
Two hundred and eight cases satisfied the criteria for grading, out of which 34.1% were classified in grade I, 32.2% in grade II and 33.7% in grade III.Soft tissue sarcomas accounted for 8.8% of malignant tumors seen over the review period (15).Another study done in Nigeria from 108 patients were diagnosed to have soft tissue sarcoma, age range was 3 to 85 years with a mean age of occurrence was 1.1years +/-18.
4 years. Rhabdomyosarcoma being the commonest variety (65.7%) fibro sarcoma 26 (24.1%), liposarcoma 6(5.6%), dermatofibrosarcoma 4(3.7%) and angiosarcoma the least occurring (0.
9%). The anatomical sites involved were, thighs 32 (29.6%) , head and neck 16 (14.8%) , arms 10 (9.3%) , buttocks 11 (10.
2%) , legs 11 (10.2%) , abdomen 9 (8.3%) , chest 7 (6.5%) , back 5 (4.
6%) ,forearm 5(4.6%) and retroperitonuem2 (1.9%). Rhabdomyosarcoma made up two thirds of the soft tissue sarcomas found and the thighs were the commonest site of involvement (16). A five years retrospective study done on cytopathology patterns of soft tissue sarcoma in Ethiopian shows total of 15 361 patients 623 (4.1%) were included in the study in whom 516 (82.
8%) benign, 88 (14.1%) malignant and 19 (3.1%) suspicious lesions were identified. Benign tumors were relatively common in the fourth and fifth decades of life (30±49 years; 233/516: 45.1%), while the majority of soft tissue sarcomas (77/88: 87.5%) occurred in patients less than 50 years of age; about half (36/88: 40.
9%) were children and young adults less than 20 years of age. More than two thirds (364/516: 70.5%) of benign soft tissue tumors were lipomas, and 46/516 (8.9%) were neurogenic tumors, including 39 neurofibromas and seven benign schwannomas.
The most frequently diagnosed malignant soft tissue tumors were soft tissue sarcomas (56/88: 63.7%). There were 32 type-specific malignant soft tissue tumors, including 13 dermatofibrosarcomas (DFS), eight malignant fibrous histiocytomas (MFH) and three fibro sarcomas (FS), one case each of neurofibrosarcoma, myxoid liposarcoma, angiosarcoma and alveolar rhabdomyosarcoma (RMS), and four cases of embryonal RMS. Benign tumors were roughly equally distributed across all parts of the body, with a slight predilection for the upper parts of the body, in the head and neck (135/516: 26.2%) and the trunk region (136/516: 26.4%) especially for the lipomas.
Commonest site of involvement for malignant lesions was the lower extremities (32/88: 36.4%). These included 21 non-specific malignant soft tissue tumors and 11 type-specific sarcomas (six MFH, two FS and one each of angiosarcoma, DFS and alveolar RMS). There were 19 soft tissue tumors that were diagnosed as suspicious, of which seven were diagnosed as spindle cell neoplasms and eight as simply mesenchymal neoplasms. (17).Significance of the studyDespite cases are reported frequently in study area Histological patterns of sarcoma let alone in jimma; it’s very few as a whole in Ethiopia and very limited in Africa. Having this I am enthusiastic in studying patterns of soft tissue malignancies in JUMC, hoping that this research may help as foot step for further studies, and provide information’s regarding Soft tissue malignancies for institutions, journals and policy makersSo this study is believed to identify the commonest Soft tissue malignancies in JUMC with in last five years. Objectives General objectives• To describe the histopathology pattern of malignant soft tissue tumors in Jimma University Medical Center, 2010 from 2004 to 2009 E.
CSpecific objectives1. To describe the histopathology patterns of malignant soft tissue tumors with respect to residence 2. To assess the histopathology patterns of malignant soft tissue tumors with respect sex3.
To determine the histopathology patterns of malignant soft tissue tumors with respect to age of the patient4. To assess the histopathology patterns of malignant soft tissue tumors with respect to the topology of the tumor.Methods and materials Study area and study periodThe study will be conducted in Jimma University medical center (JUMC), Pathology department. It is teaching hospital situated in Jimma town 345KM south west of central city. JUMC is the only teaching and referral hospital in southwest region and Pathology department in JUMC is providing a comprehensive range of services both to the hospital, to the south west part of the country in large and to the local primary care sectors since its establishment in 1985 G.
C There is Fine Needle Aspiration Cytology (FNAC) services and histopathology services in the hospital. The study will be conducted from September 1 -30, 2010Study design Descriptive cross sectional study design will be used PopulationSource populationAll soft tissue tumor biopsy of patients sent to JUMC, Pathology departmentStudy populationAll malignant soft tissue tumor biopsy of patients during the five years duration (2004-2009 E.C) which fulfills the inclusion criteria.
Sample sizeAll biopsy samples with soft tissue tumors recorded on registration and logbook during the last five years (2004-2009) will be reviewed.Sampling techniquesFirst, all biopsy records with soft tissue from Pathology department filled on biopsy request form and logbook during the last five years (2004-2009) will be identified. Second, among all identified soft tissue tumor biopsy records, records with malignant soft tissue tumors diagnosis will also be identified.Finally, those biopsy records with malignant soft tissue tumors will be reviewed consecutively for all important variables. Inclusion and Exclusion criteriaInclusion criteriaAll soft tissue biopsy records with all important variables such as age, sex, sites, residence and diagnosis.Soft tissue related biopsy samples sent for histopathology studyExclusion criteriaRecords which missed at least one of important variables and records with no diagnosis Data collection techniquesData extraction checklist will be prepared for extraction of important variables from the records.
Data will be extracted by trained five histopathology technicians.Data quality assuranceTo assure the quality of data, before the actual data collection, situational analysis will be conducted to look at the records. Afterwards missed variables will be included into the extraction checklist and unimportant variables will be excluded. A two days training will also be provided for the data extractors.
Variables Dependent variables – Type of the tumor – Site of the tumor Independent variables- Age of the patient- Sex of the patient- Address of the patient Data analysisData will be entered into Epi data v.3.1. and exported to SPSS V.20 for analysis. Before analysis data cleaning will be done to make the data ready for analysis. Descriptive analysis such as frequency, proportions, mean and standard deviation will be used for analysis.
Finally result will be presented using tables, graphs or in narrative form. Ethical considerationEthical clearance will be obtained from Institutional Review Board (IRB) of JUMC. Permission to conduct study will also be submitted to pathology department. All records will be retrieved by unique identifier rather than the patient name to keep confidentiality. WORK PLANActivities Responsible bodies Months(2010/2011 E.C) May June July August Sep Oct Nov Dec Topic selection PI Development of proposal PI; AD 1stdraft submission PI Final proposal submission PI Data collection PI ; DC Data compilation and analysis PI ;AD Submission of final report PI Dissemination of the result PI PI- Principal Investigator, AD-Advisor, DC – data collectorBudget break downS.no Budget category List of respective category Unit Unit price (birr) Multiplying factors (quantity) Total(birr)1 Personal Data collector 12345 300300300300300 300*10300*10300*10300*10300*10 30003000300030003000 Secretary 1 1000 1000 1000 Data analyzer 2 3000 3000*2 6000 Sub total 22,0002 Stationary Duplicating paper 1 packet 100 100 Duplicating ink 1 200 200 Pens 2 2 2*5 10 CD-RW 2 25 25*2 50 Pencils 5 1 1*5 5 Ruler 5 5 5*5 25 Eraser 5 2 5*2 10 Sharpener 2 5 2*5 10 Sub total 410Grand total 22,410 Ethiopian birrDummy tables Table 1: Frequency distribution of patients by sex No.
%sex Female Male Table 2: Frequency distribution of patients by ageAge group No %70 Table 4 Frequency distribution of tumors by residencyResidence No. %Urban Rural Table 4 Frequency distribution of tumors by locationSites of tumor No. %Lower limb Upper limb Head and neck Trunk Pelvis Retroperitoneal others Tables 5: Frequency distribution of tumors by typesTumors No. %Benign Malignant Table 6; Frequency distribution of tumors grades of tumors Grades No. %High grade Intermediate grades Low grades Table 7; Frequency distribution of tumors by histopathology patternspatterns No. %Liposarcoma Leimyosarcoma MFH Rhabdomyosarcoma Malignant PNST Synovial sarcoma Dermatofibrosarcoma protuberance Fibro sarcoma Others References 1. Rosa J, Ackerman. Soft tissues.
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Volume 14, Issue 4 Ver. IX (Apr. 2015), PP 47-49 17. Cytological diagnosis of soft tissue tumors M.
BEZABIH Department of Pathology Jimma University, Ethiopia; January (2001) Check list format Age ______________________ Sex_______________________Residence ______________Site of the tumor__________________Diagnosis———————————————————————————————————————————————————————-Collected by——————————-Date ———————————