The Journal of Dennatology Vol. 17: 414-422,1990
Kaposi's Sarcoma: A Light and Electron Microscopic Study Haruhisa Kato, Toshio Hamada, Takuo Tsuji*, Takashi Baba**,jun-ichi Seki*** and Yasutsugu Kobayashi**** Abstract
A patient with diabetes mellitus who developed the typical classic lesions of Kaposi's sarcoma is described. Our patient presented with a reddish-purple papulonodular lesion on the right foot of five months' duration. A skin biopsy specimen showed a proliferation of spindle cells forming numerous vascular slits and a diffuse extravasation of erythrocytes. The patient's sera was negative for human immunodeficiency virus (HIV) antibodies and cytomegalovirus (CMV) antibodies. Ultrastructural examination demonstrated fibroblast-like spindle cells phagocytosing and digesting red blood cells to form vascular spaces. The patient died, due to gastrointestinal hemorrhage, and the autopsy revealed an extensive visceral involvement of Kaposi's sarcoma.
Key words:
Kaposi's sarcoma; diabetes mellitus; ultrastructure; autopsy
Introduction Kaposi's sarcoma, originally described by Kaposi in 1872, is an unusual multicentric neoplastic disorder with unknown etiology characterized by proliferation of vascular spaces and spindle-shaped cells. It usually appears as asymptomatic purple to violaceous or reddish-brown maculopapular lesions on the lower extremities, primarily in men over the age of 60, and may become nodules or plaques. Histologically, proliferation of small vessels, increased numbers of spindle cells and macrophages with hemosiderin deposits, and extravasation of erythrocytes are common features. Recent observations have revealed that acquired immune deficiency syndrome (AIDS) may accompany Kaposi's sarcoma. Kaposi's Received January 26, 1990; accepted for publication April 4, 1990. Department of Dermatology, Osaka City University Medical School, Osaka,Japan. *Department of Dermatology, Nagoya City University Medical School, Nagoya,japan. **Divisions of Dermatology and ***Intemal Medicine, Osaka Municipal Momoyama Citizen Hospital, Osaka, japan. ****Division of Pathology, Children's Medical Center of Osaka City, Osaka,japan. Reprint requests to: Haruhisa Kato, Division of Dermatology, Hoshigaoka Koseinenkin Hospital, 4-8-1, Hoshigaoka, Hirakata 573,japan.
Fig. 1. Appearance of lesion on the right foot. Multiple, reddish-purple papulonodular eruptions are seen. sarcoma in the AIDS patient is distinct from previously reported forms of this disease in its clinical presentation, extensive visceral involvement, and poor prognosis. We report herein a classical Kaposi's sarcoma with a rapid and widespread visceral involvement occurring in a 69-year-old japanese man and review the japanese cases of Kaposi's sarcoma.
Report of a Case A 69-year-old man was referred to us for evaluation of slowly growing, painful, papulonodular eruptions on his right foot in September of 1985,which had developed five months earlier. He had suffered from diabetes mellitus for more than a decade and
Kaposi's Sarcoma
415
Fig. 2. Appearance of lesion on the left foot. Reddish-purple papulonodular eruptions are seen.
Fig. 3. An autopsy finding from the ileum. Multiple, hemorrhagic nodular lesions are seen.
been treated with an oral hypoglycemic agent; his fasting blood sugar was around 200 mg/dl. He also complained of pain and soreness over the right leg when walking. There was no past history of homosexual or multiple sexual contact. On physical examination, various sized (up to 2 ern), slightly indurated, firm, reddish-purple papules and nodules were scattered over the right dorsal foot. Some necrotic lesions were seen, but no blisters (Fig. 1). The right foot had a lower temperature than the left foot. The arteria dorsalis pedis of the right foot pulsed regularly. Digital subtraction angiography of both legs showed no vascular anomalies. A biopsy specimen from the papular lesion on the right foot showed proliferation of spindle cells and extravasation of erythrocytes, compatible with Kaposi's sarcoma. In November of 1986, the pain in both legs had become intense, and the patient was admitted to Osaka Municipal Momoyama Citizens Hospital, Osaka, japan. Results oflaboratory studies disclosed a white blood cell count of 4,400/mm' and a red blood cell count of 424 x 104/ mm' . The hemoglobin level was 11.5 g/dl and the results of routine chemistries were normal, except for an increased blood sugar level, 326 mg/dl. Immunofluorescence studies with antibodies to human T-cell lymphotropic virus (HTLV-l), human immunodeficiency virus (HIV), and cytomegalovirus (CMV) were negative. Six months after hospital admission, the lesions on the right foot had extended rapidly to the sole with moderate to severe edema which caused in-
tense pain and disturbance of gait. Combined chemotherapy with vincristine (1.1 mg/week) and a 5-day course of actinomycin D (0.125 mg/day) was instituted. However, the patient followed a progressively downhill course with new cutaneous lesions (Fig. 2), and he died in November of 1987. An autopsy was performed. Widespread Kaposi's sarcoma was identified in the gastrointestinal tract, diaphragm, and adrenal glands (Fig. 3). Examination of multiple lymph nodes disclosed extensive replacement of the nodal architecture by Kaposi's sarcoma. The immediate cause of death was overwhelming gastrointestinal bleeding.
Materials and Methods A biopsy specimen taken from a representative papular lesion at the initial presentation was processed for light and electron microscopic examination. A formalin-fixed, paraffin-embedded specimen was cut 7-J1.m thick and stained with hematoxylin and eosin. For ultrastructural investigation, the specimen was fixed with 2.5% glutaraldehyde and post-fixed with 1% osmium tetroxide in phosphate buffer solution (pH 7.4). Routine methods were used for dehydration, embedding, thin sectioning, and staining. The sections were examined in a Hitachi H-300 electron microscope. At autopsy, specimens were taken from skin, lymph nodes, and other visceral organs including gastrointestinal tract, lung, adrenal glands, and bone marrow, and submitted for light microscopic examination.
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Fig. 4. Histology of the biopsy specimen showed dense aggregates of spindle cells, capillaries, and extravasated erythrocytes within a circumscribed area surrounded by a thick fibrotic wall in the upper to middle dermis (H&E; x90).
Fig. 5. There are many thin-walled, rudimentary vascular channels surrounded by closely packed spindle cells (H&E; x180).
Kaposi's Sarcoma
Fig. 6. A mitotic figure (arrowhead) is seen (H&E; x360).
Fig. 7. A photomicrograph of a postmortem specimen taken from one of the nodules in the ileum. Numerous vascular channels are embedded in an edematous stroma (H&E; x180).
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Fig. 8. Electron micrograph of the lesion of the foot. Each aggregate demonstrated in Figure 4 is composed of spindle cells, erythrocytes, and incomplete vascular lumina (L).
Results Light microscopic findings: A biopsy specimen from a representative papular lesion at the initial presentation showed a proliferation of endothelial cells, interweaving fascicles or spindle cells, and extravasated erythrocytes in the upper to deep dermis (Fig. 4). There were numerous narrow vascular spaces or vascular slits containing erythrocytes. All neoplastic vascular structures were bizarre in shape, and thin-walled rudimentary spaces were seen within aggregates of neoplastic cells (Fig. 5). Cytologic atypia was not prominent; few mitotic figures were seen (Fig. 6). At the periphery of the aggregates, there were widely dilated endothelial-lined spaces (Fig. 5). There were only sparse inflammatory infiltrates. Postmortem examination of internal viscera, including esophagus, small intestine, colon, and adrenal gland, revealed similar histologic
findings. The visceral organs were infiltrated by Kaposi's sarcoma, showing collections of vascular channels and spindle cells embedded in a rather edematous stroma (Fig. 7). The cells comprising these vessels had large nuclei with one or two distinct nucleoli, protruding into the lumen. Nuclear atypia was minimal and few mitotic figures were observed. Electron microscopic findings: There were various degrees of development of blood vessels ranging from incomplete to relatively complete ones. In the incomplete blood vessels, endothelial cells had a large irregular nucleus with peripherally condensed chromatin and prominent nucleoli (Fig. 8). There were a few cytoplasmic organelles in such endothelial cells; no Weibel-Palade bodies were seen. These cells formed incomplete lumina and had discontinuous basal lamina. Intercellular junctions were poorly formed, as was the basal lamina. Erythrophagocytosis was a prominent feature;
Kaposi's Sarcoma
419
Fig. 9. Crumpled remnants of erythrocyte membrane (M) are seen in an endothelial cell. Peripheral to the endothelium lies a discontinuous basal lamina (arrow).
some endothelial cells contained residues of red blood cells (Fig. 9). Fibroblast-like cells, macrophages, and pericytes were the most likely candidates involved in erythrophagocytosis. Whole or parts of the phagocytosed erythrocytes were seen within the cytoplasm. Some of them contained crumpled erythrocyte membranes, representing an advanced stage of erythrophagocytosis (Fig. 10). The number of phagocytosed erythrocytes varied, ranging from one to many per cell. In relatively complete blood vessels, endothelial cells had a rather small regular nucleus and well-developed cell organelles, including Weibel-Palade bodies (Fig. 11). Some endothelial cells protruded into the vascular lumen and contained nuclear bodies. However, the tubuloreticular structures usually seen in the AIDS-associated variant of Kaposi's sarcoma were absent.
Comment
The present article describes a rare case of Kaposi's sarcoma recently seen in Japan. Kaposi's sarcoma was first described in 1872 by Moricz Kaposi as a malignant neoplastic process of the skin and internal organs. Classically, it appears as dark-blue to red-purple macules, plaques, or nodules on the feet. The disease is usually seen in elderly men ofJewish, Italian, Mediterranean, or black ancestry (1-3); Japanese cases of Kaposi's sarcoma are very rare. Fujii et al. (4) reviewed fifteen cases of Kaposi's sarcoma reported in the Japanese literature, including the diagnostic, histologic, and clinical findings. Six more cases of classical Kaposi's sarcoma have appeared in the Japanese literature since then (5-9), and we add another. Among all the Japanese cases, the ages of the patients ranged from 8 to 87 with a mean of 52. Male to female patient ratio was 13:9. The
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Kato et al
Fig. 10. A fibroblast-like cell is engaged in erythrophagocytosis. Note the extensive cisternae of rough endoplasmic reticulum. Crumpled membrane of erythrocytes is seen (M).
lesions were composed of multiple reddish purple papules and nodules, mainly distributed over the legs and feet. The development of Kaposi's sarcoma is usually linked with a state of immunodepression, in the classic form as well as in the AIDSassociated variant. Seroepidemiologic analyses have shown a specific association of CMV with Kaposi's sarcoma in the cases reported in Europe, Africa, and the USA. Serum antibodies to CMV have also been detected in patients with classic Kaposi's sarcoma (10-12). Our patient was negative for CMV antibody and showed no clinical CMV involvement. Diabetes mellitus seems to be one of Kaposi's sarcoma's predisposing factors (13). Dysfunctions of immunocompetence in diabetics may play an essential role in the development of this disease. Morphologic features of Kaposi's sarcoma
seen in the histologic sections vary from stage to stage of the disease's chronologie development. The histology of nodular or plaque lesions of Kaposi's sarcoma includes fibroblastic and neovascular proliferation, extravasated erythrocytes, and hemosiderin deposits. The characteristic vascular slit pattern, the presence of erythrocytes in clefts between the neoplastic spindle cells, is one important clue that aids in diagnosis. At this stage, spindle cells show cytologic atypia, pleomorphism, and mitotic figures in large numbers. The present case displayed spindle cells forming interweaving fascicles with erythrocytes in the interstrices between the spindle cells. Mitotic figures were sometimes encountered; however, cytologic atypia was minimal. Ultrastructurally, major features of Kaposi's sarcoma are a proliferation of immature vascular channels, and endothelial and fibroblast-
Kaposi's Sarcoma
421
Fig. 11. Endothelial cells have a large nucleus and protrude into the lumen (L). Inset: High power view of one of the endothelial cells. Weibel-Palade bodies (W) are seen.
like spindle cells. Extravasation of erythrocytes is a common finding. Erythrophagocytosis, most often by endothelial cells but also by pericytes and fibroblasts, is a distinctive feature in the later nodular stage. Hypertrophied endothelial cells with increased mitotic activity, often containing nuclear bodies, are a common feature. Surrounding the endothelial cells, there is a basal lamina which is frequently fragmented and discontinuous. Tubuloreticular structures are found only in the AIDSassociated form of Kaposi's sarcoma, not in the classical form of the tumor (14, 15). The most prominent ultrastructural features of the present case were erythrophagocytosis by the neoplastic spindle cells and endothelial cells and a proliferation of primitive vessels. Crumpled membranes of erythrocytes were seen in some of the fibroblast-like cells and endothelial cells, representing an advanced stage of erythrophagocytosis. However, the
tubuloreticular structures seen in the AIDSassociated form of Kaposi's sarcoma were absent. The age of the onset of the disease (late sixties), slowly growing clinical course, results of immunofluorescence studies (negative HIV antibody), and absence oftubuloreticular structures confirmed a diagnosis of classic Kaposi's sarcoma. References 1) Cox FH, Helwig EB: Kaposi's sarcoma, Cancer, 12: 289-298, 1959. 2) Herring BD: Kaposi's sarcoma in the Negro,jAMA, 185:540-542,1966. 3) Friedman-Birnbaum R, Weltfriend S, Katz I: Kaposi's sarcoma: Retrospective study of 67 cases with the classical form, Dermatologica, 180: 13-17, 1990. 4) Fujii Y, Takayasu S, Yokoyama S, Eizuru Y, Minamishima Y, Enjoji M: Kaposi's sarcoma in a Korean living in Japan: Review of cases reported in Japanese literature,] Am AcadDermatol, 15: 76-82, 1986.
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Kato et al
5) Yamada H, Tsunoda T, Mitsuhashi Y, Furukawa T, Okuyama H: A case of Kaposi's sarcoma, jpn j Dermatol, 91: 1013,1981. (in Japanese) 6) Sasaki K, Tanaka S, Watanabe S, Yabumoto E: Kaposi's sarcoma and its management of radiotherapy,Jpnj Dermatol, 95: 1379, 1985. (in Japanese) 7) Uyesato H, Miyasato H, Shinei H, et al: A case of Kaposi's sarcoma in association with multiple myeloma,jpnj Dermatol, 96: 541, 1986. (in Japanese) 8) Takahashi Y, Ando M, Tsukinaga I, Kobayashi H, Kumakiri M: A case of Kaposi's sarcoma, jpn j Dermatol, 97: 615, 1987. (in Japanese) 9) Ando M, Takahashi Y, Kaneko F, et al: Two cases of Kaposi's sarcoma,jpnj Dermatol, 97: 1483-1484,1987. (in Japanese) 10) Giraldo G, Beth E, Kourilsky FM, et al: Antibody patterns to herpesviruses in Kaposi's sarcoma: Serological association of European Kaposi's sarcoma with cytomegalovirus, IntjCancer, 15: 839-848, 1975.
11) Giraldo G, Beth E, Henle W, et al: Antibody patterns to herpesviruses in Kaposi's sarcoma with cytomegalovirus, Intj Cancer, 22: 126-131, 1978. 12) Boldogh I, Beth E, Huang E-S, Kyalwazi KS, Giraldo G: Kaposi's sarcoma: IV. Detection of CMV DNA, CMV RNA and CMNA in tumor biopsies, Intj Cancer, 28: 469-474, 1981. 13) Hurlbut WB, Lincoln CS: Multiple hemorrhagic sarcoma and diabetes mellitus, Arch Int Med, .84: 738-750,1949. 14) Konrad K, Schenk P, Rappersberger K: Tubuloreticular structures in Kaposi's sarcoma: A comparison of the classical and AIDS-associated forms, Acta Derm Venereol (Stockh), 66: 207-212, 1986. 15) Berk MA, Medenica M, Laumann A: Tubuloreticular structures in a papular eruption associated with human immunodeficiency virus disease, j Am Acad Dermatol, 18: 452-456, 1988.
Kaposi's Sarcoma: A Light and Electron Microscopic Study Haruhisa Kato, Toshio Hamada, Takuo Tsuji*, Takashi Baba**,jun-ichi Seki*** and Yasutsugu Kobayashi**** Abstract
A patient with diabetes mellitus who developed the typical classic lesions of Kaposi's sarcoma is described. Our patient presented with a reddish-purple papulonodular lesion on the right foot of five months' duration. A skin biopsy specimen showed a proliferation of spindle cells forming numerous vascular slits and a diffuse extravasation of erythrocytes. The patient's sera was negative for human immunodeficiency virus (HIV) antibodies and cytomegalovirus (CMV) antibodies. Ultrastructural examination demonstrated fibroblast-like spindle cells phagocytosing and digesting red blood cells to form vascular spaces. The patient died, due to gastrointestinal hemorrhage, and the autopsy revealed an extensive visceral involvement of Kaposi's sarcoma.
Key words:
Kaposi's sarcoma; diabetes mellitus; ultrastructure; autopsy
Introduction Kaposi's sarcoma, originally described by Kaposi in 1872, is an unusual multicentric neoplastic disorder with unknown etiology characterized by proliferation of vascular spaces and spindle-shaped cells. It usually appears as asymptomatic purple to violaceous or reddish-brown maculopapular lesions on the lower extremities, primarily in men over the age of 60, and may become nodules or plaques. Histologically, proliferation of small vessels, increased numbers of spindle cells and macrophages with hemosiderin deposits, and extravasation of erythrocytes are common features. Recent observations have revealed that acquired immune deficiency syndrome (AIDS) may accompany Kaposi's sarcoma. Kaposi's Received January 26, 1990; accepted for publication April 4, 1990. Department of Dermatology, Osaka City University Medical School, Osaka,Japan. *Department of Dermatology, Nagoya City University Medical School, Nagoya,japan. **Divisions of Dermatology and ***Intemal Medicine, Osaka Municipal Momoyama Citizen Hospital, Osaka, japan. ****Division of Pathology, Children's Medical Center of Osaka City, Osaka,japan. Reprint requests to: Haruhisa Kato, Division of Dermatology, Hoshigaoka Koseinenkin Hospital, 4-8-1, Hoshigaoka, Hirakata 573,japan.
Fig. 1. Appearance of lesion on the right foot. Multiple, reddish-purple papulonodular eruptions are seen. sarcoma in the AIDS patient is distinct from previously reported forms of this disease in its clinical presentation, extensive visceral involvement, and poor prognosis. We report herein a classical Kaposi's sarcoma with a rapid and widespread visceral involvement occurring in a 69-year-old japanese man and review the japanese cases of Kaposi's sarcoma.
Report of a Case A 69-year-old man was referred to us for evaluation of slowly growing, painful, papulonodular eruptions on his right foot in September of 1985,which had developed five months earlier. He had suffered from diabetes mellitus for more than a decade and
Kaposi's Sarcoma
415
Fig. 2. Appearance of lesion on the left foot. Reddish-purple papulonodular eruptions are seen.
Fig. 3. An autopsy finding from the ileum. Multiple, hemorrhagic nodular lesions are seen.
been treated with an oral hypoglycemic agent; his fasting blood sugar was around 200 mg/dl. He also complained of pain and soreness over the right leg when walking. There was no past history of homosexual or multiple sexual contact. On physical examination, various sized (up to 2 ern), slightly indurated, firm, reddish-purple papules and nodules were scattered over the right dorsal foot. Some necrotic lesions were seen, but no blisters (Fig. 1). The right foot had a lower temperature than the left foot. The arteria dorsalis pedis of the right foot pulsed regularly. Digital subtraction angiography of both legs showed no vascular anomalies. A biopsy specimen from the papular lesion on the right foot showed proliferation of spindle cells and extravasation of erythrocytes, compatible with Kaposi's sarcoma. In November of 1986, the pain in both legs had become intense, and the patient was admitted to Osaka Municipal Momoyama Citizens Hospital, Osaka, japan. Results oflaboratory studies disclosed a white blood cell count of 4,400/mm' and a red blood cell count of 424 x 104/ mm' . The hemoglobin level was 11.5 g/dl and the results of routine chemistries were normal, except for an increased blood sugar level, 326 mg/dl. Immunofluorescence studies with antibodies to human T-cell lymphotropic virus (HTLV-l), human immunodeficiency virus (HIV), and cytomegalovirus (CMV) were negative. Six months after hospital admission, the lesions on the right foot had extended rapidly to the sole with moderate to severe edema which caused in-
tense pain and disturbance of gait. Combined chemotherapy with vincristine (1.1 mg/week) and a 5-day course of actinomycin D (0.125 mg/day) was instituted. However, the patient followed a progressively downhill course with new cutaneous lesions (Fig. 2), and he died in November of 1987. An autopsy was performed. Widespread Kaposi's sarcoma was identified in the gastrointestinal tract, diaphragm, and adrenal glands (Fig. 3). Examination of multiple lymph nodes disclosed extensive replacement of the nodal architecture by Kaposi's sarcoma. The immediate cause of death was overwhelming gastrointestinal bleeding.
Materials and Methods A biopsy specimen taken from a representative papular lesion at the initial presentation was processed for light and electron microscopic examination. A formalin-fixed, paraffin-embedded specimen was cut 7-J1.m thick and stained with hematoxylin and eosin. For ultrastructural investigation, the specimen was fixed with 2.5% glutaraldehyde and post-fixed with 1% osmium tetroxide in phosphate buffer solution (pH 7.4). Routine methods were used for dehydration, embedding, thin sectioning, and staining. The sections were examined in a Hitachi H-300 electron microscope. At autopsy, specimens were taken from skin, lymph nodes, and other visceral organs including gastrointestinal tract, lung, adrenal glands, and bone marrow, and submitted for light microscopic examination.
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Kato et al
Fig. 4. Histology of the biopsy specimen showed dense aggregates of spindle cells, capillaries, and extravasated erythrocytes within a circumscribed area surrounded by a thick fibrotic wall in the upper to middle dermis (H&E; x90).
Fig. 5. There are many thin-walled, rudimentary vascular channels surrounded by closely packed spindle cells (H&E; x180).
Kaposi's Sarcoma
Fig. 6. A mitotic figure (arrowhead) is seen (H&E; x360).
Fig. 7. A photomicrograph of a postmortem specimen taken from one of the nodules in the ileum. Numerous vascular channels are embedded in an edematous stroma (H&E; x180).
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Kato et al
Fig. 8. Electron micrograph of the lesion of the foot. Each aggregate demonstrated in Figure 4 is composed of spindle cells, erythrocytes, and incomplete vascular lumina (L).
Results Light microscopic findings: A biopsy specimen from a representative papular lesion at the initial presentation showed a proliferation of endothelial cells, interweaving fascicles or spindle cells, and extravasated erythrocytes in the upper to deep dermis (Fig. 4). There were numerous narrow vascular spaces or vascular slits containing erythrocytes. All neoplastic vascular structures were bizarre in shape, and thin-walled rudimentary spaces were seen within aggregates of neoplastic cells (Fig. 5). Cytologic atypia was not prominent; few mitotic figures were seen (Fig. 6). At the periphery of the aggregates, there were widely dilated endothelial-lined spaces (Fig. 5). There were only sparse inflammatory infiltrates. Postmortem examination of internal viscera, including esophagus, small intestine, colon, and adrenal gland, revealed similar histologic
findings. The visceral organs were infiltrated by Kaposi's sarcoma, showing collections of vascular channels and spindle cells embedded in a rather edematous stroma (Fig. 7). The cells comprising these vessels had large nuclei with one or two distinct nucleoli, protruding into the lumen. Nuclear atypia was minimal and few mitotic figures were observed. Electron microscopic findings: There were various degrees of development of blood vessels ranging from incomplete to relatively complete ones. In the incomplete blood vessels, endothelial cells had a large irregular nucleus with peripherally condensed chromatin and prominent nucleoli (Fig. 8). There were a few cytoplasmic organelles in such endothelial cells; no Weibel-Palade bodies were seen. These cells formed incomplete lumina and had discontinuous basal lamina. Intercellular junctions were poorly formed, as was the basal lamina. Erythrophagocytosis was a prominent feature;
Kaposi's Sarcoma
419
Fig. 9. Crumpled remnants of erythrocyte membrane (M) are seen in an endothelial cell. Peripheral to the endothelium lies a discontinuous basal lamina (arrow).
some endothelial cells contained residues of red blood cells (Fig. 9). Fibroblast-like cells, macrophages, and pericytes were the most likely candidates involved in erythrophagocytosis. Whole or parts of the phagocytosed erythrocytes were seen within the cytoplasm. Some of them contained crumpled erythrocyte membranes, representing an advanced stage of erythrophagocytosis (Fig. 10). The number of phagocytosed erythrocytes varied, ranging from one to many per cell. In relatively complete blood vessels, endothelial cells had a rather small regular nucleus and well-developed cell organelles, including Weibel-Palade bodies (Fig. 11). Some endothelial cells protruded into the vascular lumen and contained nuclear bodies. However, the tubuloreticular structures usually seen in the AIDS-associated variant of Kaposi's sarcoma were absent.
Comment
The present article describes a rare case of Kaposi's sarcoma recently seen in Japan. Kaposi's sarcoma was first described in 1872 by Moricz Kaposi as a malignant neoplastic process of the skin and internal organs. Classically, it appears as dark-blue to red-purple macules, plaques, or nodules on the feet. The disease is usually seen in elderly men ofJewish, Italian, Mediterranean, or black ancestry (1-3); Japanese cases of Kaposi's sarcoma are very rare. Fujii et al. (4) reviewed fifteen cases of Kaposi's sarcoma reported in the Japanese literature, including the diagnostic, histologic, and clinical findings. Six more cases of classical Kaposi's sarcoma have appeared in the Japanese literature since then (5-9), and we add another. Among all the Japanese cases, the ages of the patients ranged from 8 to 87 with a mean of 52. Male to female patient ratio was 13:9. The
420
Kato et al
Fig. 10. A fibroblast-like cell is engaged in erythrophagocytosis. Note the extensive cisternae of rough endoplasmic reticulum. Crumpled membrane of erythrocytes is seen (M).
lesions were composed of multiple reddish purple papules and nodules, mainly distributed over the legs and feet. The development of Kaposi's sarcoma is usually linked with a state of immunodepression, in the classic form as well as in the AIDSassociated variant. Seroepidemiologic analyses have shown a specific association of CMV with Kaposi's sarcoma in the cases reported in Europe, Africa, and the USA. Serum antibodies to CMV have also been detected in patients with classic Kaposi's sarcoma (10-12). Our patient was negative for CMV antibody and showed no clinical CMV involvement. Diabetes mellitus seems to be one of Kaposi's sarcoma's predisposing factors (13). Dysfunctions of immunocompetence in diabetics may play an essential role in the development of this disease. Morphologic features of Kaposi's sarcoma
seen in the histologic sections vary from stage to stage of the disease's chronologie development. The histology of nodular or plaque lesions of Kaposi's sarcoma includes fibroblastic and neovascular proliferation, extravasated erythrocytes, and hemosiderin deposits. The characteristic vascular slit pattern, the presence of erythrocytes in clefts between the neoplastic spindle cells, is one important clue that aids in diagnosis. At this stage, spindle cells show cytologic atypia, pleomorphism, and mitotic figures in large numbers. The present case displayed spindle cells forming interweaving fascicles with erythrocytes in the interstrices between the spindle cells. Mitotic figures were sometimes encountered; however, cytologic atypia was minimal. Ultrastructurally, major features of Kaposi's sarcoma are a proliferation of immature vascular channels, and endothelial and fibroblast-
Kaposi's Sarcoma
421
Fig. 11. Endothelial cells have a large nucleus and protrude into the lumen (L). Inset: High power view of one of the endothelial cells. Weibel-Palade bodies (W) are seen.
like spindle cells. Extravasation of erythrocytes is a common finding. Erythrophagocytosis, most often by endothelial cells but also by pericytes and fibroblasts, is a distinctive feature in the later nodular stage. Hypertrophied endothelial cells with increased mitotic activity, often containing nuclear bodies, are a common feature. Surrounding the endothelial cells, there is a basal lamina which is frequently fragmented and discontinuous. Tubuloreticular structures are found only in the AIDSassociated form of Kaposi's sarcoma, not in the classical form of the tumor (14, 15). The most prominent ultrastructural features of the present case were erythrophagocytosis by the neoplastic spindle cells and endothelial cells and a proliferation of primitive vessels. Crumpled membranes of erythrocytes were seen in some of the fibroblast-like cells and endothelial cells, representing an advanced stage of erythrophagocytosis. However, the
tubuloreticular structures seen in the AIDSassociated form of Kaposi's sarcoma were absent. The age of the onset of the disease (late sixties), slowly growing clinical course, results of immunofluorescence studies (negative HIV antibody), and absence oftubuloreticular structures confirmed a diagnosis of classic Kaposi's sarcoma. References 1) Cox FH, Helwig EB: Kaposi's sarcoma, Cancer, 12: 289-298, 1959. 2) Herring BD: Kaposi's sarcoma in the Negro,jAMA, 185:540-542,1966. 3) Friedman-Birnbaum R, Weltfriend S, Katz I: Kaposi's sarcoma: Retrospective study of 67 cases with the classical form, Dermatologica, 180: 13-17, 1990. 4) Fujii Y, Takayasu S, Yokoyama S, Eizuru Y, Minamishima Y, Enjoji M: Kaposi's sarcoma in a Korean living in Japan: Review of cases reported in Japanese literature,] Am AcadDermatol, 15: 76-82, 1986.
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Kato et al
5) Yamada H, Tsunoda T, Mitsuhashi Y, Furukawa T, Okuyama H: A case of Kaposi's sarcoma, jpn j Dermatol, 91: 1013,1981. (in Japanese) 6) Sasaki K, Tanaka S, Watanabe S, Yabumoto E: Kaposi's sarcoma and its management of radiotherapy,Jpnj Dermatol, 95: 1379, 1985. (in Japanese) 7) Uyesato H, Miyasato H, Shinei H, et al: A case of Kaposi's sarcoma in association with multiple myeloma,jpnj Dermatol, 96: 541, 1986. (in Japanese) 8) Takahashi Y, Ando M, Tsukinaga I, Kobayashi H, Kumakiri M: A case of Kaposi's sarcoma, jpn j Dermatol, 97: 615, 1987. (in Japanese) 9) Ando M, Takahashi Y, Kaneko F, et al: Two cases of Kaposi's sarcoma,jpnj Dermatol, 97: 1483-1484,1987. (in Japanese) 10) Giraldo G, Beth E, Kourilsky FM, et al: Antibody patterns to herpesviruses in Kaposi's sarcoma: Serological association of European Kaposi's sarcoma with cytomegalovirus, IntjCancer, 15: 839-848, 1975.
11) Giraldo G, Beth E, Henle W, et al: Antibody patterns to herpesviruses in Kaposi's sarcoma with cytomegalovirus, Intj Cancer, 22: 126-131, 1978. 12) Boldogh I, Beth E, Huang E-S, Kyalwazi KS, Giraldo G: Kaposi's sarcoma: IV. Detection of CMV DNA, CMV RNA and CMNA in tumor biopsies, Intj Cancer, 28: 469-474, 1981. 13) Hurlbut WB, Lincoln CS: Multiple hemorrhagic sarcoma and diabetes mellitus, Arch Int Med, .84: 738-750,1949. 14) Konrad K, Schenk P, Rappersberger K: Tubuloreticular structures in Kaposi's sarcoma: A comparison of the classical and AIDS-associated forms, Acta Derm Venereol (Stockh), 66: 207-212, 1986. 15) Berk MA, Medenica M, Laumann A: Tubuloreticular structures in a papular eruption associated with human immunodeficiency virus disease, j Am Acad Dermatol, 18: 452-456, 1988.
