Perivascular Epithelioid Cell Tumors

Background

The perivascular epithelioid cell (PEC) gives rise to a variety of tumors having a clear cytoplasmic apperance and showing strong immunopositivity for HMB-45, a marker which is relatively specific for melanoma. However, it is clear that these tumors are not melanomas. These tumors are often associated with patients having tuberous sclerosis. Although tumors occurring in organs as varied as the kiendy and liver were once thought be benign, it is becoming increasingly clear that PEC tumors (PEComas) should be regarded as a tumor of uncertain malignant potential. Longer term follow up should resolve these issues of borderline cases.

CLINICAL VARIANTS CHARACTERIZATION

ABDOMENOPELVIC SARCOMA

Abdominopelvic Sarcoma of Perivascular Epithelioid Cells. Report of Four Cases in Young Women, One with Tuberous Sclerosis

Franco Bonetti, M.D., Guido Martignoni, M.D., Chiara Colato, M.D., Erminia Manfrin, M.D., Marcello Gambacorta, M.D., Maurizio Faleri, M.D., Carlos Bacchi, M.D., Vai-Chong Sin, MBBS, Nim-Lai Wong, M.D., Mark Coady, M.D. and John Kwok-cheung Chan, M.D.

Istituto di Anatomia Patologica (FB, GM, EM, CC), Università di Verona; Servizio di Anatomia Patologica (MG, MF), Ospedale Niguarda, Milano, Italy; Department of Pathology (CB), Facultade Medicina-UNESP Botucatu, Brasil; Department of Pathology and Clinical Oncology (VCS, JKCC), Queen Elizabeth Hospital, Hong Kong; Department of Anatomical Pathology (MC), SEALS Prince of Wales Hospital, Sidney, Australia; and Department of Pathology (NLW), Kinag Wu Hospital, Macau

Mod Pathol 2001;14:563-568 Abstract quote

The perivascular epithelioid cell has been proposed to be the unifying proliferating cell type in a number of lesions such as angiomyolipoma, lymphangiomyomatosis, clear cell "sugar" tumor and renal capsuloma. With the exception of rare examples of angiomyolipoma, they are non-metastasizing.

We report four examples of a new member of this family of perivascular epithelioid cell neoplasms that occur in abdominopelvic location and show metastatic properties.

The patients, all women, were aged 19 to 41 years (mean, 32), and presented with a tumor mass involving the serosa of the ileum, uterus or pelvic cavity. Morphologically, the tumors were composed of sheets of large polygonal cells with glycogen-rich clear or eosinophilic cytoplasm and moderately pleomorphic nuclei, traversed by a delicate vasculature, mimicking clear cell carcinoma. There were areas of coagulative necrosis and occasional mitotic figures. Intracytoplasmic brown pigment was present in two cases. Spindly cells, smooth muscle and fat were absent. Lymphovascular invasion was present in all, lymph node metastasis was documented in two and metastasis to the ovary was present in one case.

Two patients developed widespread metastatic disease after 10 and 28 months from diagnosis. One patient showed the clinical signs of tuberous sclerosis. In spite of the epithelial-like appearance, the tumor cells were negative for epithelial markers but were strongly positive with the melanogenesis-related marker HMB45. Another melanogenesis marker (MART-1) was positive in two cases. Other markers including S-100 protein, vimentin, muscle-specific actin, desmin and chromogranin A were negative.

Thus, these tumors are not readily classifiable in the existing schema of known entities, and show overlapping morpho-phenotypic features of clear cell "sugar" tumor of the lung and epithelioid angiomyolipoma. We consider them as sarcomas composed of a pure population of uncommitted perivascular epithelioid cell, that lack modulation toward smooth muscle or adipose cells.

BREAST

Clear cell 'sugar' tumor of the breast: another extrapulmonary site and review of the literature.

Govender D, Sabaratnam RM, Essa AS.

Department of Pathology, Nelson R. Mandela School of Medicine, University of Natal, Durban, South Africa.

Am J Surg Pathol 2002 May;26(5):670-5 Abstract quote
A group of lesions show morphologic and immunophenotypic evidence of differentiation toward a putative perivascular epithelioid cell. These so-called PEComas include angiomyolipoma, lymphangiomyoma, lymphangioleiomyomatosis, renal capsuloma, clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres, and clear cell "sugar" tumor. PEComas are characterized by strong immunoreactivity with the HMB45 antibody and variable expression of muscle markers. This family of lesions may be composed of a spectrum of cells from epithelioid to spindle cells with clear to granular eosinophilic cytoplasm. One member of this family, composed of epithelioid cells with glycogen-rich clear cytoplasm, is descriptively called a clear cell "sugar" tumor. This tumor, originally described in the lung, is being recognized increasingly in extrapulmonary sites.

We report a case of a primary extrapulmonary clear cell "sugar" tumor occurring in the right breast of a 16-year-old girl. The tumor was composed of clear epithelioid cells with abundant glycogen and distinct cell borders. The tumor showed strong immunoreactivity with HMB45 antibody and Melan-A. There was focal vimentin staining. In addition, there was diffuse and strong nuclear staining for progesterone receptor. Antibodies to actins, S-100 protein, cytokeratins (AE1/AE3 and CAM5.2), desmin, and estrogen receptor were negative. The tumor was completely excised, and the patient is well without evidence of disease 9 months postexcision.

FALCIFORM LIGAMENT

Clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres: a novel member of the perivascular epithelioid clear cell family of tumors with a predilection for children and young adults.

Folpe AL, Goodman ZD, Ishak KG, Paulino AF, Taboada EM, Meehan SA, Weiss SW.

Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA. .

Am J Surg Pathol 2000 Sep;24(9):1239-46 Abstract quote
The perivascular epithelioid cell family of tumors (PEComas), defined by their co-expression of melanocytic and muscle markers, includes angiomyolipoma, lymphangioleiomyoma, and clear cell "sugar" tumors of the lung, pancreas, and uterus.

We present seven cases of a unique and previously unrecognized tumor of children and young adults, which represents a new addition to the PEComa group of tumors. Culled from three institutions over a 50-year period, all cases occurred in or immediately adjacent to the ligamentum teres and falciform ligament. Six patients were female and one male; their ages ranged from 3 to 21 years (median, 11 yrs). Tumor sizes ranged from 5 to 20 cm (median, 8 cm). All cases consisted of clear to faintly eosinophilic spindled cells arranged in fascicular and nested patterns. The cells had small but distinct nucleoli and low mitotic activity. Immunohistochemically, all cases were positive with antibodies to gp100 protein (HMB-45) and negative for S-100 protein. In three of the seven cases studied immunohistochemically, the tumors expressed smooth muscle actin, melan-A, microphthalmia transcription factor (MiTF), and myosin, but not desmin. No expression of the TSC2 gene product, tuberin, was seen in three cases. One case studied cytogenetically disclosed a t(3;10). Follow-up data, available in six of seven cases (median duration, 18 mos), showed five patients to be free of disease and one to have a radiographically presumed lung metastasis.

We think these tumors comprise a new entity for which we propose the term "clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres." The differential diagnosis of these tumors includes clear cell sarcoma of tendons and aponeuroses, leiomyosarcoma, and angiomyolipoma.

KIDNEY

Angiomyolipoma

LUNG

Clear cell tumor of the lung (sugar tumour). Study of a case
Eichler B, Loubet A, Leboutet MJ, Germouty J, Loubet R.

Service d'Anatomie Pathologique 1 et Microscopie Electronique, CHU Dupuytren, Limoges.

Arch Anat Cytol Pathol 1991;39(3):83-7 Abstract quote

A case of benign clear cell tumor ("sugar tumor") is reported. Light microscopy showed a proliferation of clear cells with a rich blood supply and endocrinoid pattern. Ultrastructurally, cells were loaded with glycogen both free and membrane-bound.

The cellular origin of the benign clear cell tumor of the lung is still uncertain.

Benign clear cell tumor of the lung in an 8-year-old girl.

Fukuda T, Machinami R, Joshita T, Nagashima K.

Arch Pathol Lab Med 1986 Jul;110(7):664-6 Abstract quote

A case of "benign clear cell tumor of the lung" occurred in an 8-year-old girl. The tumor was a solid well-circumscribed mass, measuring 1 cm in diameter. Histologically, it consisted of polygonal cells intermingled with large, thin-walled vessels. Glycogen was scarce in paraffin sections; however, electron microscopic observation revealed a large amount of glycogen. Intracytoplasmic filaments were not observed, but scattered pinocytotic vesicles and plaquelike densities along the plasma membrane were found.

Lymphangioleiomyomatosis

UTERUS
Most patients present with abnormal uterine bleeding with a mass in the uterine corpus

Group A tumors have a tounge-like growth pattern similar to low-grade endometrial stromal sarcoma with abundant clear to eosinophilic pale cytoplasm, diffuse HMB-45 expression and focal muscle marker expression

Group B tumors had epithelioid cells with less abundant clear cytoplasm, lesser numbers of cells with HMB-45 expression, extensive muscle marker expression,a nd lesser degress of endometrial stromal sarcoma growth pattern

Epithelioid lymphangioleiomyomatosis-like tumor of the uterus in a patient without tuberous sclerosis: a lesion mimicking epithelioid leiomyosarcoma

Histopathology 1998;33:91-93

Hyalinized uterine mesenchymal neoplasms with HMB-45 positive epithelioid cells: epithelioid leiomyomas or angiomyolipoma? Report of four cases

Michal M, Zamecnik M

Int J Surg Pathol 2000;8:323-328

Perivascular Epithelioid Cell Tumor (`PEComa') of the Uterus A Subset of HMB-45-Positive Epithelioid Mesenchymal Neoplasms With an Uncertain Relationship to Pure Smooth Muscle Tumors

Russell Vang, M.D. ; Richard L. Kempson, M.D.

From the Department of Pathology (Laboratory of Surgical Pathology), Stanford University Medical Center, Stanford, California, U.S.A.

Am J Surg Pathol 2002;26:1-13 Abstract quote

The family of lesions thought to be composed at least in part of perivascular epithelioid cells, characterized as HMB-45-positive epithelioid cells with clear to eosinophilic granular cytoplasm and a propensity for a perivascular distribution, includes some forms of angiomyolipoma and lymphangioleiomyomatosis, as well as clear cell “sugar” tumor (CC-SUGAR). When composed predominantly or exclusively of epithelioid cells, it has been suggested that these lesions be classified as “perivascular epithelioid cell tumors” (PEComa). Four cases of uterine PEComa have been described in the literature, three of which exhibited aggressive behavior.

We report the clinical, histologic, and immunohistochemical features of eight more examples of uterine PEComa. Patients ranged in age from 40 to 75 years (mean 54 years). Most patients presented because of abnormal uterine bleeding, and grossly a mass was present in the uterine corpus. Morphologically, the tumors could be divided into two groups (A and B). Group A tumors demonstrated a tongue-like growth pattern similar to that seen in low-grade endometrial stromal sarcoma and were composed of cells that tended to have abundant clear to eosinophilic pale granular cytoplasm, diffuse HMB-45 expression, and focal muscle marker expression. Group B tumors were composed of epithelioid cells with less prominent clear cell features, smaller numbers of which were HMB-45-positive. They also featured extensive muscle marker expression and a lesser degree of the endometrial stromal sarcoma growth pattern seen in group A tumors. Two of the four patients with group B tumors had pelvic lymph nodes involved by lymphangioleiomyomatosis, and one of these patients had the tuberous sclerosis complex. Seven of the eight patients with PEComas were treated by hysterectomy. All eight patients are alive and well, although follow-up of >2 years was available only for two patients.

Uterine epithelioid smooth muscle tumors and low-grade endometrial stromal sarcomas were compared with the PEComas. Group A PEComas, group B PEComas, and epithelioid smooth muscle tumors were all parts of a continuous histologic spectrum, with group A PEComa at one end of the spectrum and epithelioid smooth muscle tumors at the other, while group B tumors shared features of both. PEComa was histologically and immunohistochemically distinct from endometrial stromal sarcoma.

Our data and a review of the literature indicate that PEComa is a subset of HMB-45-positive epithelioid mesenchymal tumors of the uterus with an uncertain relationship to pure smooth muscle tumors. Although none of the patients in this study experienced recurrence during a short follow-up period, some reported in the literature have had recurrences; consequently, we think uterine PEComa should be considered a tumor of uncertain malignant potential until long-term outcome data for a larger number of patients become available.

OTHER

Primary Extrapulmonary Sugar Tumor (PEST): A Report of Four Cases

Henry D. Tazelaar, M.D., Kenneth P. Batts, M.D. and John R. Srigley, M.D.

Department of Laboratory Medicine and Pathology, Mayo Clinic (HDT), Rochester, Minnesota; Abbott Northwestern Hospital (KPB), Minneapolis, Minnesota; and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada and the Credit Valley Hospital, Mississauga, Ontario, Canada (JRS)

Mod Pathol 2001;14:615-622 Abstract quote

The cell of origin and direction of differentiation of the clear cell tumor of the lung (the so-called sugar tumor) remains enigmatic. Recognition of HMB-45 immunoreactivity and identification of melanosomes have suggested a relationship to angiomyolipoma of kidney or liver and lymphangiomyoma. This has given rise to the concept that clear cell tumors are neoplasms of so-called perivascular epithelioid cells—PEComas.

Herein we report the existence of four similar tumors occurring in extrapulmonary sites, one of which had malignant features. The three benign tumors occurred in females ages 9, 20, and 40 years; two were located in the rectum and one in the vulva. The malignant tumor occurred in the inter-atrial cardiac septum of a 29-year-old man. Common histologic features were a richly vascular organoid architecture, tumor cells with clear to pale eosinophilic cytoplasm, abundant glycogen, and immunoreactivity for HMB 45, but not S100, multiple keratin, neuroendocrine, or muscle markers. Benign tumors demonstrated low mitotic activity, no necrosis, and good circumscription; the malignant tumor showed considerable mitotic activity, necrosis, and an infiltrative growth pattern. Ultrastructurally, glycogen was present, mitochondria were abundant, and membrane-bound lamellated bodies consistent with premelanosomes were present in two cases, and equivocal in one. Because these tumors have light microscopic, immunohistochemical, and electron microscopic features similar to pulmonary sugar tumors, we propose the name primary extrapulmonary sugar tumor (PEST) for them. Although most PEST’s are probably benign, malignant forms appear to exist.

These cases further support the concept of a family of systemic HMB-45 positive tumors that include sugar tumors, angiomyolipoma of kidney or liver, lymphangiomyomas, and clear-cell myomelanocytic tumors of the falciform ligament/ligamentum teres.

SPECIAL STAINS/IMMUNOHISTOCHEMICAL STAINS/
ELECTRON MICROSCOPY CHARACTERIZATION

POSITIVE HMB-45
CD10

NEGATIVE S-100
Mart-1
Desmin
Actin
Keratin
Inhibin
CD34

Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.

Commonly Used Terms

Tuberous Sclerosis

Last Updated 5/16/2002

CLINICAL VARIANTS	CHARACTERIZATION
ABDOMENOPELVIC SARCOMA
Abdominopelvic Sarcoma of Perivascular Epithelioid Cells. Report of Four Cases in Young Women, One with Tuberous Sclerosis Franco Bonetti, M.D., Guido Martignoni, M.D., Chiara Colato, M.D., Erminia Manfrin, M.D., Marcello Gambacorta, M.D., Maurizio Faleri, M.D., Carlos Bacchi, M.D., Vai-Chong Sin, MBBS, Nim-Lai Wong, M.D., Mark Coady, M.D. and John Kwok-cheung Chan, M.D. Istituto di Anatomia Patologica (FB, GM, EM, CC), Università di Verona; Servizio di Anatomia Patologica (MG, MF), Ospedale Niguarda, Milano, Italy; Department of Pathology (CB), Facultade Medicina-UNESP Botucatu, Brasil; Department of Pathology and Clinical Oncology (VCS, JKCC), Queen Elizabeth Hospital, Hong Kong; Department of Anatomical Pathology (MC), SEALS Prince of Wales Hospital, Sidney, Australia; and Department of Pathology (NLW), Kinag Wu Hospital, Macau	Mod Pathol 2001;14:563-568 Abstract quote The perivascular epithelioid cell has been proposed to be the unifying proliferating cell type in a number of lesions such as angiomyolipoma, lymphangiomyomatosis, clear cell "sugar" tumor and renal capsuloma. With the exception of rare examples of angiomyolipoma, they are non-metastasizing. We report four examples of a new member of this family of perivascular epithelioid cell neoplasms that occur in abdominopelvic location and show metastatic properties. The patients, all women, were aged 19 to 41 years (mean, 32), and presented with a tumor mass involving the serosa of the ileum, uterus or pelvic cavity. Morphologically, the tumors were composed of sheets of large polygonal cells with glycogen-rich clear or eosinophilic cytoplasm and moderately pleomorphic nuclei, traversed by a delicate vasculature, mimicking clear cell carcinoma. There were areas of coagulative necrosis and occasional mitotic figures. Intracytoplasmic brown pigment was present in two cases. Spindly cells, smooth muscle and fat were absent. Lymphovascular invasion was present in all, lymph node metastasis was documented in two and metastasis to the ovary was present in one case. Two patients developed widespread metastatic disease after 10 and 28 months from diagnosis. One patient showed the clinical signs of tuberous sclerosis. In spite of the epithelial-like appearance, the tumor cells were negative for epithelial markers but were strongly positive with the melanogenesis-related marker HMB45. Another melanogenesis marker (MART-1) was positive in two cases. Other markers including S-100 protein, vimentin, muscle-specific actin, desmin and chromogranin A were negative. Thus, these tumors are not readily classifiable in the existing schema of known entities, and show overlapping morpho-phenotypic features of clear cell "sugar" tumor of the lung and epithelioid angiomyolipoma. We consider them as sarcomas composed of a pure population of uncommitted perivascular epithelioid cell, that lack modulation toward smooth muscle or adipose cells.
BREAST
Clear cell 'sugar' tumor of the breast: another extrapulmonary site and review of the literature. Govender D, Sabaratnam RM, Essa AS. Department of Pathology, Nelson R. Mandela School of Medicine, University of Natal, Durban, South Africa.	Am J Surg Pathol 2002 May;26(5):670-5 Abstract quote A group of lesions show morphologic and immunophenotypic evidence of differentiation toward a putative perivascular epithelioid cell. These so-called PEComas include angiomyolipoma, lymphangiomyoma, lymphangioleiomyomatosis, renal capsuloma, clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres, and clear cell "sugar" tumor. PEComas are characterized by strong immunoreactivity with the HMB45 antibody and variable expression of muscle markers. This family of lesions may be composed of a spectrum of cells from epithelioid to spindle cells with clear to granular eosinophilic cytoplasm. One member of this family, composed of epithelioid cells with glycogen-rich clear cytoplasm, is descriptively called a clear cell "sugar" tumor. This tumor, originally described in the lung, is being recognized increasingly in extrapulmonary sites. We report a case of a primary extrapulmonary clear cell "sugar" tumor occurring in the right breast of a 16-year-old girl. The tumor was composed of clear epithelioid cells with abundant glycogen and distinct cell borders. The tumor showed strong immunoreactivity with HMB45 antibody and Melan-A. There was focal vimentin staining. In addition, there was diffuse and strong nuclear staining for progesterone receptor. Antibodies to actins, S-100 protein, cytokeratins (AE1/AE3 and CAM5.2), desmin, and estrogen receptor were negative. The tumor was completely excised, and the patient is well without evidence of disease 9 months postexcision.
FALCIFORM LIGAMENT
Clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres: a novel member of the perivascular epithelioid clear cell family of tumors with a predilection for children and young adults. Folpe AL, Goodman ZD, Ishak KG, Paulino AF, Taboada EM, Meehan SA, Weiss SW. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA. .	Am J Surg Pathol 2000 Sep;24(9):1239-46 Abstract quote The perivascular epithelioid cell family of tumors (PEComas), defined by their co-expression of melanocytic and muscle markers, includes angiomyolipoma, lymphangioleiomyoma, and clear cell "sugar" tumors of the lung, pancreas, and uterus. We present seven cases of a unique and previously unrecognized tumor of children and young adults, which represents a new addition to the PEComa group of tumors. Culled from three institutions over a 50-year period, all cases occurred in or immediately adjacent to the ligamentum teres and falciform ligament. Six patients were female and one male; their ages ranged from 3 to 21 years (median, 11 yrs). Tumor sizes ranged from 5 to 20 cm (median, 8 cm). All cases consisted of clear to faintly eosinophilic spindled cells arranged in fascicular and nested patterns. The cells had small but distinct nucleoli and low mitotic activity. Immunohistochemically, all cases were positive with antibodies to gp100 protein (HMB-45) and negative for S-100 protein. In three of the seven cases studied immunohistochemically, the tumors expressed smooth muscle actin, melan-A, microphthalmia transcription factor (MiTF), and myosin, but not desmin. No expression of the TSC2 gene product, tuberin, was seen in three cases. One case studied cytogenetically disclosed a t(3;10). Follow-up data, available in six of seven cases (median duration, 18 mos), showed five patients to be free of disease and one to have a radiographically presumed lung metastasis. We think these tumors comprise a new entity for which we propose the term "clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres." The differential diagnosis of these tumors includes clear cell sarcoma of tendons and aponeuroses, leiomyosarcoma, and angiomyolipoma.
KIDNEY
Angiomyolipoma
LUNG
Clear cell tumor of the lung (sugar tumour). Study of a case Eichler B, Loubet A, Leboutet MJ, Germouty J, Loubet R. Service d'Anatomie Pathologique 1 et Microscopie Electronique, CHU Dupuytren, Limoges.	Arch Anat Cytol Pathol 1991;39(3):83-7 Abstract quote A case of benign clear cell tumor ("sugar tumor") is reported. Light microscopy showed a proliferation of clear cells with a rich blood supply and endocrinoid pattern. Ultrastructurally, cells were loaded with glycogen both free and membrane-bound. The cellular origin of the benign clear cell tumor of the lung is still uncertain.
Benign clear cell tumor of the lung in an 8-year-old girl. Fukuda T, Machinami R, Joshita T, Nagashima K.	Arch Pathol Lab Med 1986 Jul;110(7):664-6 Abstract quote A case of "benign clear cell tumor of the lung" occurred in an 8-year-old girl. The tumor was a solid well-circumscribed mass, measuring 1 cm in diameter. Histologically, it consisted of polygonal cells intermingled with large, thin-walled vessels. Glycogen was scarce in paraffin sections; however, electron microscopic observation revealed a large amount of glycogen. Intracytoplasmic filaments were not observed, but scattered pinocytotic vesicles and plaquelike densities along the plasma membrane were found.
Lymphangioleiomyomatosis
UTERUS	Most patients present with abnormal uterine bleeding with a mass in the uterine corpus Group A tumors have a tounge-like growth pattern similar to low-grade endometrial stromal sarcoma with abundant clear to eosinophilic pale cytoplasm, diffuse HMB-45 expression and focal muscle marker expression Group B tumors had epithelioid cells with less abundant clear cytoplasm, lesser numbers of cells with HMB-45 expression, extensive muscle marker expression,a nd lesser degress of endometrial stromal sarcoma growth pattern
Epithelioid lymphangioleiomyomatosis-like tumor of the uterus in a patient without tuberous sclerosis: a lesion mimicking epithelioid leiomyosarcoma	Histopathology 1998;33:91-93
Hyalinized uterine mesenchymal neoplasms with HMB-45 positive epithelioid cells: epithelioid leiomyomas or angiomyolipoma? Report of four cases Michal M, Zamecnik M	Int J Surg Pathol 2000;8:323-328
Perivascular Epithelioid Cell Tumor (`PEComa') of the Uterus A Subset of HMB-45-Positive Epithelioid Mesenchymal Neoplasms With an Uncertain Relationship to Pure Smooth Muscle Tumors Russell Vang, M.D. ; Richard L. Kempson, M.D. From the Department of Pathology (Laboratory of Surgical Pathology), Stanford University Medical Center, Stanford, California, U.S.A.	Am J Surg Pathol 2002;26:1-13 Abstract quote The family of lesions thought to be composed at least in part of perivascular epithelioid cells, characterized as HMB-45-positive epithelioid cells with clear to eosinophilic granular cytoplasm and a propensity for a perivascular distribution, includes some forms of angiomyolipoma and lymphangioleiomyomatosis, as well as clear cell “sugar” tumor (CC-SUGAR). When composed predominantly or exclusively of epithelioid cells, it has been suggested that these lesions be classified as “perivascular epithelioid cell tumors” (PEComa). Four cases of uterine PEComa have been described in the literature, three of which exhibited aggressive behavior. We report the clinical, histologic, and immunohistochemical features of eight more examples of uterine PEComa. Patients ranged in age from 40 to 75 years (mean 54 years). Most patients presented because of abnormal uterine bleeding, and grossly a mass was present in the uterine corpus. Morphologically, the tumors could be divided into two groups (A and B). Group A tumors demonstrated a tongue-like growth pattern similar to that seen in low-grade endometrial stromal sarcoma and were composed of cells that tended to have abundant clear to eosinophilic pale granular cytoplasm, diffuse HMB-45 expression, and focal muscle marker expression. Group B tumors were composed of epithelioid cells with less prominent clear cell features, smaller numbers of which were HMB-45-positive. They also featured extensive muscle marker expression and a lesser degree of the endometrial stromal sarcoma growth pattern seen in group A tumors. Two of the four patients with group B tumors had pelvic lymph nodes involved by lymphangioleiomyomatosis, and one of these patients had the tuberous sclerosis complex. Seven of the eight patients with PEComas were treated by hysterectomy. All eight patients are alive and well, although follow-up of >2 years was available only for two patients. Uterine epithelioid smooth muscle tumors and low-grade endometrial stromal sarcomas were compared with the PEComas. Group A PEComas, group B PEComas, and epithelioid smooth muscle tumors were all parts of a continuous histologic spectrum, with group A PEComa at one end of the spectrum and epithelioid smooth muscle tumors at the other, while group B tumors shared features of both. PEComa was histologically and immunohistochemically distinct from endometrial stromal sarcoma. Our data and a review of the literature indicate that PEComa is a subset of HMB-45-positive epithelioid mesenchymal tumors of the uterus with an uncertain relationship to pure smooth muscle tumors. Although none of the patients in this study experienced recurrence during a short follow-up period, some reported in the literature have had recurrences; consequently, we think uterine PEComa should be considered a tumor of uncertain malignant potential until long-term outcome data for a larger number of patients become available.
OTHER
Primary Extrapulmonary Sugar Tumor (PEST): A Report of Four Cases Henry D. Tazelaar, M.D., Kenneth P. Batts, M.D. and John R. Srigley, M.D. Department of Laboratory Medicine and Pathology, Mayo Clinic (HDT), Rochester, Minnesota; Abbott Northwestern Hospital (KPB), Minneapolis, Minnesota; and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada and the Credit Valley Hospital, Mississauga, Ontario, Canada (JRS)	Mod Pathol 2001;14:615-622 Abstract quote The cell of origin and direction of differentiation of the clear cell tumor of the lung (the so-called sugar tumor) remains enigmatic. Recognition of HMB-45 immunoreactivity and identification of melanosomes have suggested a relationship to angiomyolipoma of kidney or liver and lymphangiomyoma. This has given rise to the concept that clear cell tumors are neoplasms of so-called perivascular epithelioid cells—PEComas. Herein we report the existence of four similar tumors occurring in extrapulmonary sites, one of which had malignant features. The three benign tumors occurred in females ages 9, 20, and 40 years; two were located in the rectum and one in the vulva. The malignant tumor occurred in the inter-atrial cardiac septum of a 29-year-old man. Common histologic features were a richly vascular organoid architecture, tumor cells with clear to pale eosinophilic cytoplasm, abundant glycogen, and immunoreactivity for HMB 45, but not S100, multiple keratin, neuroendocrine, or muscle markers. Benign tumors demonstrated low mitotic activity, no necrosis, and good circumscription; the malignant tumor showed considerable mitotic activity, necrosis, and an infiltrative growth pattern. Ultrastructurally, glycogen was present, mitochondria were abundant, and membrane-bound lamellated bodies consistent with premelanosomes were present in two cases, and equivocal in one. Because these tumors have light microscopic, immunohistochemical, and electron microscopic features similar to pulmonary sugar tumors, we propose the name primary extrapulmonary sugar tumor (PEST) for them. Although most PEST’s are probably benign, malignant forms appear to exist. These cases further support the concept of a family of systemic HMB-45 positive tumors that include sugar tumors, angiomyolipoma of kidney or liver, lymphangiomyomas, and clear-cell myomelanocytic tumors of the falciform ligament/ligamentum teres.

SPECIAL STAINS/IMMUNOHISTOCHEMICAL STAINS/ ELECTRON MICROSCOPY	CHARACTERIZATION
POSITIVE	HMB-45 CD10
NEGATIVE	S-100 Mart-1 Desmin Actin Keratin Inhibin CD34