Irifune Kenji

Itakura Hideyo

Senba Masachika

Toda Yumiko

Toriyama Kan

Uzuta Fukumu

Nagasaki University's Academic Output SITE: NAOSITE

T rop. Med., 28 (Suppl.), 3-8, December, 19863Kaposi's Sarcoma: Pathology and Local Epidemiology in KenyaHideyo ITAKURA, Kan TORIYAMA, Fukumu UZUTA, Yumiko TODAKenji IRIFUNE and Masachika SENBADepartment of Pathology, Institute of Tropical MedicineNagasaki University, Nagasaki 852, JapanKaposi's sarcoma8' (KS) is regarded as being commonamongpeople in Africa.1-10) The highestincidence of KS is found around Lake Kivu, at the edge of Tropical rain forest surrounded by Zaire,Rwanda, Burundi and Uganda, and the disease accounts for up to 12.8% of all malignant tumors.There are reports that the incidence of KS increases as one approaches to the Equator. Thispresentation is mainly concerned with geographical pathology and histopathology of KS in westernKenya, and additional studies in Ghana, Tanzania, the United States and Japan.Kaposi's sarcoma in western KenyaWhat we are going to present first is the results of our investigation75 in local areas in westernKenya. Out of 23,271 surgical specimens at provincial and district hospitals in western Kenya, 107cases were diagnosed histologically as KS during the period from 1979 to 1985. The averageincidence of KS in western Kenya was 2.81% of all malignant tumors. These figures are lower thanthat in Zaire, Uganda, Malawi and Tanzania. The highest incidence of KS is found in the age groupbetween 50 and 59. The youngest was a 1 year and 6 month-old boy, and the oldest was a 72-year-oldmale. Male : female ratio was 8 : 1. Many reports from Africa showed almost the same agedistribution, and these figures are relatively younger than the classical form of KS in Europe andNorth America. These differences probably depend on the life style, hygienic conditions and lifespan in each country.In adults, the most commonsite of primary lesion was the foot, followed by the leg, hand, arm,thigh, knee and ankle. In children, on the other hand, it was the lymph nodes. The western regionof The Republic of Kenya stands almost exactly astride the equator. And it accounts for almost onethird of the whole country in area and about one half in population. Western Kenya is composedof three provinces; Nyanza, Western and Rift Valley Province. These areas show a wide variationof climatic conditions. The highest incidence of KS (1.78 per 100,000 population) is found in NyanzaProvince, where there is a tropical savannah and in the southern half, a lake basin around LakeVictoria, followed by Western Province, where there is a tropical savannah, and then Rift ValleyProvince, central and eastern parts of western Kenya being a tropical highlands.The Luo tribe, the main inhabitants of Nyanza Province around Lake Victoria, showed thehighest incidence of KS (2.40 per 100,000 population) , followed by the Luhya tribe who are the maininhabitants of Western Province. The Kisii and Teso also showed a high incidence. The Kikuyuhave the largest population of the country, but many of them are living in provinces outside westernKenya. We could not confirm the exact number of their population in western Kenya. As in KS,4the highest incidence of Burkitt's lymphoma was also seen in the Luo tribe.In the areas showing the highest incidence of KS in western Kenya, there is also a highfrequency of other tumors, such as Burkitt's lymphoma, hepatocellular carcinoma, penile cancer,and uterus cancer, which might be related to certain infectious agents. KS and Burkitt's lymphomahave relatively same geographical distribution in Africa. It is presumed that continuous foreigninfectious antigenic stimulation might cause a relative immunodeficiency in African inhabitants.Reports from Europe and North America showed that the association of KS with other malig-nancies, especially of the lymphoreticular system, such as Hodgkin's disease, malignant lymphomaand lymphocytic leukemia is not uncommon. In our series, however, we have no case of KS withother malignancies. Many reports described that genetic factors also seem to play a role in thecausation of KS. It has been reported that in Tanzania tribal concentration was observed in somesmall Bantu tribes, and on the other hand, in the Nilohamitic groups, KS was extremely rare. Inwestern Kenya, however, KS is more commonin the humid tropical savannah and on the tropicalhighlands, even among different ethnic groups. KS predominates among people in rural areas. Inadults the most commonsite of primary lesion is the foot, followed by the leg, hand, and arm. Theseregions are more exposed to the environment than other sites of the body and so are more prone tobe infected with transmissible agents. Nowadays, ethnic groups are gradually increasing culturaland marital exchanges each other, but they are still keeping their own identities and cultures,especially in the rural areas. Therefore, it is clear that they have had little chance to interminglegenetically.In our series the high incidence of KS was shown amongthe differnt ethnic groups; the Luo whobelong to the Nilotic, the Luhya who belong to Bantu, and Kalenjin who belong to Nilotic. But KSwas extremely rare among the Maasai who are Nilohamitic and Turkana who are Nilotic, bothliving in dry sandy areas. It seems that these differences of incidence among the ethnic groups aredependent on the different environmental conditions and life styles. These findings suggest thatenvironmental factors are more important in the causation of KS in Africa, although there areundoubtedly other genetic factors.Histological process:Histological process of skin lesions of African endemic KS was studied in African countriesincluding Kenya, Ghana, Tanzania and the United States by observation of different nodules of thesame patient and a lot of specimens from differnt patients at every stage of the disease. His-tologically, in ealier stages of the disease, cutaneous edema and perivascular inflammatory cellinfiltration, mainly lymphocytes and plasma cells, were observed. Lymphangiectasis was also asignificant feature. Spindle-shaped cell proliferation appeared gradually. Hemangiosarcoma-likepatterns were observed frequently in the course of the tumor. KS having an angiomatous patternmay be confused with hemangiosarcoma. In advanced stages, characteristic atypical cells withslit-like pattern (vascular cavities) were observed. The typical KS at later stages were composedof proliferating bundles of spindle-shaped cells. Collagen fibers were seen occasionally between thetumor cells. A few cases of cutaneous KS were quite anaplastic. Amongspindle-shaped cells havingrelatively abundant cytoplasm elongated cells with basophilic cytoplasm similar to anaplasticcarcinoma cells were observed.Histology in the course of African cutaneous KS can be summarized as follows: 1 ) In early5stages, cutaneous edema and perivascular inflammatory cell infiltration, mainly lymphocytes andplasma cells are seen. Lymphangiectasis is also significant feature. 2 ) Spindle-shaped cellsappears gradually. 3 ) Hemangiosarcoma-like pattern is observed in the course of the tumorfrequently. 4 ) In advanced stages, characteristic tumor cells with slit-like vascular cavities areobserved.According to these findings, cutaneous KS in Africa has characteristic features of both infec-tions and neoplasm. Majority (80%) of cutaneous KS show multicentric foci even in its earlystages. In this respect, KS is a unique disease different from other simillar diseases of soft tissuessuch as hemangioma, hemangiosarcoma, lymhangiosarcoma and malignant pericytoma.Histological classification:The essential histological features of KS are composed of spindle-shaped cells and vasculartissues. Various histological classifications of the disease have been used by many researchers. Weclassified African cutaneous KS according to the predominant components as follows: 1 )granulomatous, 2 ) hemangiosarcomatous, 3 ) fibrosarcomatous or spindle-shaped cells and 4 )anaplastic types.Additional histological findings:Another charactristic feature is the round, hyaline, eosinophilic globules of various sizes in thetumor tissue. The globules were found in some cases of African cutaneous KS, and also observedin KS of the lymph nodes. The size of the globules ranges from 1 to 10 um. The globules occur inaggregates in the intercellular spaces and/or in the cytoplasm of tumor cells.The eosinophilic globules had similar histochemical properties to the globular bodies found inyolk sac tumor and other tissues.15) They were positive in periodic acid Schiff (PAS) reaction, PASafter diastase, trypsin and neuraminidase digestion, phosphotungstic acid hematoxylin (PTAH)staining, and auto fluorescence methods. These globules were histochemically distinct from globulargiant mitochodria and Mallory's alcoholic hyaline, which were PAS negative. Orcein, resorcinfuchsin, silver impregnation and iron reaction could not stain the globules. We could not demon-strate alpha-fetoprotein, alpha-1-antitrypsin and beta-subunit of human chorionic gonadotropin inthe globules by immunoperoxidase methods. The globules were negative for Mayer's mucicarmineand alcian blue. These results suggest that the globules are glycoprotein.Histogenesis:Considering histogenesis of KS,3'n> the immunoperoxidase technique was performed to thecutaneous type of KS to examine factor VIII-related antigen. Positve staining was demonstratedin only mature endothelial cells in our series.Three forms of KS: African endemic, Classical, and AIDSAfter the evolution of AIDS, Pneumocystis carinii pneumonia and KS have been reported as themost common"marker" diseases of AIDS.4-5-6-9'13'14) KS in AIDS shows a wide variety of clinicalmanifestations and some cases with flat and hemorrhagic skin lesions are different in appearancefrom African endemic KS. KS in AIDS also show a wide variety of histological features. Althoughsomelesions of KS in AIDS show remarkable proliferation of spindle-shaped cells similar to African6cutaneous KS, some of them have abundant vascular channels like the appearance of capillaryhemangioma or hemangiosarcoma. Vascular endothelial cells of KS in AIDS show a wide varietyof atypism. African endemic cutaneous KS in adults are usually long standing, growing slowly, andoccasionally regressive. In our series, the longest one had a 20 year duration, and clinically it wasnot aggressive or fatel. KS in AIDS can show African KS-like manifestations. However, accordingto our experiences, the fact was not vice versa except in rare cases. Same cases of classicalcutaneous KS of white adults showing multiple small nodules in the lower legs were examinedhistologically. The lesions were nearly the same as the African cutaneous form, although interlac-ing spindle-shaped cells were somewhat loose in density. As for lymph node lesions of African KSin children, proliferation of spindle-shaped cells with relatively abundant cytoplasm were observedand this type of KS seemed relatively aggressive. Lymph node lesions of adult African endemic KSshowed almost the same features as African pediatric cases. Lymph node lesions in some cases ofKS in AIDS were only angiogenetic rather than typical KS and were observed mainly at thecapsular or pericapsular connective tissue of the lymph nodes.These results suggest that clinical manifestations and histological features of three forms of KSare not necessarily the same, although fundamental histological pattern is proliferation of spindle-shaped cells with abundant vascular channels. African endemic cutaneous KS are occasionallyfibrosarcomatous predominant, while some of KS in AIDS are hemangiomatous or hemaniosar-comatous predominant.Epidemiology:Finally, it must be helpful to find out the etiological factors or cofactors to conductepidemiological studies on KS in not only endemic and epidemic areas but also non-endemic andnon-epidemic areas.2'12) We have observed angiogenetic lesions in the retroperitoneal lymph nodesof a postmortem case of Japanese hemophiliac AIDS patient. We think these KS or KS-like lesionsarising in Japanese AIDS patients are very significant, because KS has been quite rare in the Orient.These findings suggest that there may be activation of some agents in AIDS or immunosuppresiveconditions119 leading to the induction of angiogenetic lesions or KS even among inhabitants ofhistorically non-endemic and non-epidemic areas of the world.Acknowledgments:This report is the outcome of our medical investigation research conducted mainly in Kenya.These>studies were supported in part by the Grant-in Aid for Overseas Research Promotion,Ministry of Education, Science and Culture, Government of Japan and performed for a few monthseach year during the period 1978 to 1985. The data in part were obtained during the period from1974 to 1975, under the Japan-Kenya Medical Cooperation Program organized by Japan Interna-tional Cooperation Agency (JICA). Throughout the whole period of this investigation, we receivedthe full support of Government of Kenya (Research Permit No. OP. 13/001/8c224/12,36). We wouldalso like to express our sincere gratitude to concerned authorities and institutions in Ghana,Tanzania, Zaire, the United States of America and Japan.cutaneous edemagranulomatous lesion\ \-> angiosarcoma-like lesion >x' ->\ > fibrosarcoma-like lesion >7FIG, 1, CUTANEOUS KAPOSI'S SARCOMA, HISTOLOGICALLY, IN EARLYSTAGES OF THE DISEASE, CUTANEOUS EDEMA AND PERIVASCULARINFLAMMATORY CELL INFILTRATION. MAINLY LYMPHOCYTES ANDPLASMA CELLS ARE SEEN, LYMPHANGIECTASIS IS ALSOSIGNIFICANT FEATURE, SPINDLE-SHAPED CELL PROLIFERATIONAPPEARS GRADUALLY, IN SOME CASES, HEMANGIOSARCOMA-LIKEPATTERN IS OBSERVED IN THE COURSE OF THE TUMOR, INADVANCED STAGES, CHARACTERISTIC SARCOMA CELLS WITHSLIT-LIKE VASCULAR CAVITIES ARE OBSERVED,TABLE 1, Characterization of eosinophilic globulesGlobules PAS D-PAS Trichrom PTAHKaposi'ssarcomaAlpha-l-antitrypsinYolk sac tumorHepatocetlularcarcinomaLung carcinomaBreastcarcinomaRenal cellcarcinomaGiantmitochondria+ ++ 4-à"f ++ +-f- ++ +4- +Auto- Immuno-reactivityfluorescence AFP AAT hCGRedRedRedNDNDNDNDRed ND+ 4- ND+ + --f 4- N DND ND NDND ND NDNDND ND NDPAS; PERIODIC ACID $CHIFF, D-PAS: PERIODIC ACID SCHIFF WITH DIASTASEDIGESTION, PTAH: PHOSPHOTUNGSTIC ACID HEMATOXYLIN, AFP: ALPHA-FETOPROTEIN,AAT: ALPHA-1-ANTITRYPSIN, HCG: HUMAN CHORIONIC GONADOTROPIN,+! POSITIVE, -I NEGATIVE, ND: NOT DONE8\References1 ) Bayley, A. C. (1984) : Aggressive Kaposi's sarcoma in Zambia. Lancet I, 1318-1320.2 ) Bayley, A. C., Downing, R.G., Cheingsong-Popov, R., Tedder, R.S., Dalgleish, A.G., & Weiss, R.A. (1985) : HTLV-III serology distinguishes atypical and endemic Kaposi's sarcoma in Africa.Lancet I, 359-361.3) Beckstead, J. H., Wood, G. S. & Fletcher, V. (1985) : Evidence for the origin of Kaposi'ssarcoma from lymphatic endothelium. Amer. J. Pathol, 119, 294-300.4 ) CDC (1981) : Kaposi's sarcoma and Pneumocystis pneumonia among homosexual men-NewYork City and California. MMWR, 30, 305-308.5 ) Gottlieb, G. J. & Ackerman, A. B. (1982) : Kaposi's sarcoma : An extensively disseminatedform in young homosexual men. Human PathoL, 13(10), 882-892.6 ) Hymes, K. B., Cheung, T., Greene, J. B., Prose, N. S., Marcus, A., Ballard, H., William, D. C. &Laubenstein, L. (1981) : Kaposi's sarcoma in homosexual men-Areport of eight cases. LancetII,598-600.7) Itakura, H. & Toriyama, K. (1985) : Pathology of Kaposi's sarcoma. Dept. PathoL, Inst. Trop.Med., Nagasaki Univ., Nagasaki.8) Kaposi, M. (1872) : Idiopathisches multiples Pigmentsarkom der Haut. Arch. Dermat. Syph., 4,265-273.9) Krigel, R. L. & Friedman-Kien, A. E. (1985) : Kaposi's sarcoma inAIDS, pp 185-211. In V. T.DeVita, Jr., S. Hellman & S. A. Rosenberg (ed.). AIDS-etiology, diagnosis, treatment, andprevention. J. B. Lippincott Co., New York.10) Kungu, A & Gatei, D. G. (1981) : Kaposi's sarcoma in Kenya. Antibiotics Chemother., 29, 38-55.ll) McNutt, N. S., Fletcher, V. & Conant, M. A. (1983) : Early lesions of Kaposi's sarcoma inhomosexual men : An ultrastructural comparison with other vascular proliferations in skin.Amer. J. PathoL, 111, 62-67.12) Oettle, A. G. (1962) : Geographical and racial differences in the frequency of Kaposi's sarcomaas evidence of environmental or genetic causes. Acta Un. Int. Cancr., 18, 330-363.13) Ross, R. K., Casagrande, J.T., Dworsky, R. L., Levine, A., & Mack, T. (1985) : Kaposi'ssarcoma in Los Angeles, California. JNCI, 75, 1011-1015.14) Safai, B. (1985) : Kaposi's sarcoma and other neoplasms in acquired immunodeficiencysyndrome, pp 59-73. In J. I. Gallin & A. S. Fauci (ed.). Advances in Host Defense Mechanisms(Vol. 5) - Acquired Immunodeficiency Syndrome. Raven Press, New York.15) Senba, M., Itakura, H., Toriyama, K. & Uzuta, F. (1984) : Periodic acid Schiff (PAS) andphosphotungstic acid hematoxylin (PTAH) positive materials in cutaneous type of Kaposi'ssarcoma. Trop. Med., 26(2), 87-91.16) Ulbright, T. M. & Santa Cruz, D. J. (1981) : Kaposi's sarcoma : Relationship with hematologic,lymphoid, and thymic neoplasia. Cancer, 47, 963-973.

Kaposi\u27s Sarcoma : Pathology and Local Epidemiology in Kenya

https://nagasaki-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=25090&item_no=1&attribute_id=18&file_no=1

Kaposi\u27s Sarcoma : Pathology and Local Epidemiology in Kenya

Abstract

Similar works

Full text

Available Versions

Nagasaki University's Academic Output SITE: NAOSITE