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.
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PATHOGENESIS CHARACTERIZATION GENERAL
- Comparative genomic hybridization study of perivascular epithelioid cell tumor: molecular genetic evidence of perivascular epithelioid cell tumor as a distinctive neoplasm.
Pan CC, Jong YJ, Chai CY, Huang SH, Chen YJ.
Department of Pathology, National Yang-Ming University, Taipei, Taiwan; Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan.
Hum Pathol. 2006 May;37(5):606-12. Abstract quote
Perivascular epithelioid cell tumor (PEComa) is a neoplasm composed chiefly of HMB-45-positive epithelioid cells with clear to granular cytoplasm and a perivascular distribution. Such tumors have been reported in different organs under a variety of designations.
The cytogenetic features of these neoplasms have not been well studied. We collected 9 tumors (5 of kidney, 1 of prostate, 1 of urinary bladder, 1 of the pelvic cavity soft tissue, and 1 of uterus) from 8 patients, including one patient with tuberous sclerosis complex. The paraffin blocks of tumor tissue were submitted for comparative genomic hybridization analyses.
Gross chromosomal aberrances were observed in all cases. The frequent imbalances were losses on chromosome 19 (8 cases), 16p (6 cases), 17p (6 cases), 1p (5 cases), and 18p (4 cases) and gains on chromosome X (6 cases), 12q (6 cases), 3q (5 cases), 5 (4 cases), and 2q (4 cases). The frequent deletion of 16p in which TSC2 gene is located indicates the oncogenetic relationship of PEComas with angiomyolipoma as a TSC2-linked neoplasm.
From a molecular genetic perspective, the recurrent chromosomal alterations in both renal and extrarenal tumors further support the concept of PEComa as a distinctive tumor entity regardless of anatomic location.
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.
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.
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.
- Digestive PEComas: a solution when the diagnosis fails to "fit".
Genevay M, Mc Kee T, Zimmer G, Cathomas G, Guillou L.
Institut Universitaire de Pathologie, Lausanne, Switzerland.
Ann Diagn Pathol. 2004 Dec;8(6):367-72. Abstract quote
We report two cases of digestive/intra-abdominal PEComa. The first lesion developed in the caecum of a 36-year-old woman, the second in the pararectal region of a 35-year-old woman. The first tumor was formed from spindle cells arranged in fascicles, the second contained predominantly epithelioid cells with prominent nucleoli.
Immunohistochemically, tumor cells expressed smooth muscle actin and melanocyte markers (HMB45), S-100 protein and CD117 were negative. Based on the morphologic aspect and, above all, on the immunohistochemical study the diagnosis of PEComa was retained for both lesions.
In the gastrointestinal tract, the principal differential diagnoses of PEComas are gastrointestinal stromal tumors, particularly the round cell/epithelioid subtype, and metastases of carcinoma and melanoma. Other differential diagnoses include rhabdomyosarcoma, paraganglioma, leiomyosarcoma, and clear cell sarcoma.
KIDNEY Angiomyolipoma LIVER
- Arch Pathol Lab Med. 2006 Aug;130(8):1219-22. Abstract quote
Neoplasms of perivascular epithelioid cells (PEComas) have in common the coexpression of muscle and melanocytic immunohistochemical markers. Although this group includes entities with distinct clinical features, such as angiomyolipoma, clear cell sugar tumor of the lung, and lymphangioleiomyomatosis, similar tumors have been documented in an increasing diversity of locations. The term PEComa is now generally used in reference to these lesions that are not angiomyolipomas, clear cell sugar tumors, or lymphangioleiomyomatoses. While most reported PEComas have behaved in a benign fashion, malignant PEComas have occasionally been documented.
We present a case of hepatic PEComa with benign histologic features, which nonetheless presented with metastases to multiple sites nearly 9 years later.
This case represents the second documented malignant PEComa of the liver, as well as the longest follow-up of a surviving patient with a malignant PEComa, emphasizing both the need for criteria that more accurately predict the behavior of PEComas and the necessity of long-term follow-up of patients with PEComas.
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.
- Perivascular epithelioid cell tumor of the oral mucosa.
Koutlas IG, Pambuccian SE, Jessurun J, Manivel JC, Gopalakrishnan R.
Division of Oral Pathology, University of Minnesota, Minneapolis 55455, USA.
Arch Pathol Lab Med. 2005 May;129(5):690-3. Abstract quote
Perivascular epithelioid cell tumors (PEComas) are a family of tumors defined by the coexpression of melanocytic and muscle markers. Examples have been reported in many organs, soft tissues, and bone.
Further expanding the list of locations, we report a case arising in the hard palate. Histologically, the tumor was composed of large elongated or epithelioid cells with granular cytoplasm. Immunohistochemically, tumor cells were positive for HMB-45, Melan A/MART-1, CD10, smooth muscle actin, desmin, and calponin. Ultrastructural examination revealed stage I melanosomes, thin filaments, and dense plaques. Recurrence has not been reported after 20 months.
To our knowledge, this is the first detailed description of an intraoral PEComa.
- Ann Diagn Pathol. 2006 Dec;10(6):352-6 Abstract quote
We report a case of diffuse myomelanocytic tumor of the peritoneum that simulates, clinically and instrumentally, a malignant mesothelioma.
The patient was a 70-year-old woman with a history of ancient hysterectomy for fibroids, who presented with abdominal discomfort. Exploratory laparotomy revealed diffuse encasing of the peritonealized organs by a thin, fleshy, gray-white tissue rind. Scattered tumor masses were present as well. A dominant lesion measuring 6 cm in larger size was resected from the pelvis.
Histological examination revealed a tumor composed of epithelioid and spindle cells, exhibiting either a clear or slightly eosinophilic cytoplasm and a mild to moderate nuclear pleomorphism. Focal areas of necrosis could be documented. Immunohistochemically, tumor cells were positive for HMB45, melan-A, and smooth muscle actin, but negative for other antibodies, including epithelial markers, desmin, and S100 protein.
We believe that this case represents an example of myomelanocytic tumor of uncertain biologic potential, a member of the recently devised perivascular epithelioid cell tumors (PEComa), with an unusual presentation simulating a diffuse mesothelial neoplasm. The origin of this particular lesion is briefly discussed in light of the recent literature published on the subject.
- Malignant perivascular epithelioid cell tumor ('PEComa'): a case report and literature review of cutaneous/subcutaneous presentations.
Department of Pathology University of South Florida College of Medicine, Tampa, FL, USA.
- J Cutan Pathol. 2008 May;35(5):499-503. Abstract quote
Perivascular epithelioid cell (PEC) tumors, also called 'PEComas,' are distinct tumors showing PEC differentiation with characteristic histologic and immunophenotypic features. PEComas are rare tumors documented in the literature presenting in numerous anatomic sites including the thorax, abdomen, pelvis, soft tissue and skin. Criteria for malignancy does not exist for the subset of PEComas that pursue an aggressive clinical course.
Herein, we present an unusual case of a malignant PEC tumor presenting as a scalp nodule in a patient with a prior diagnosis of 'melanoma' based upon the immunophenotypic profile of an excised enlarged cervical lymph node.
The purpose of this case presentation is to further describe the rare clinical manifestations of a subcutaneous PEC tumor, emphasize the malignant potential of this entity, and review the literature focusing upon clinicopathologic features of cutaneous/subcutaneous PEComas.
- Primary Cutaneous PEComa: Distinctive Clear Cell Lesions of Skin.
*Department of Pathology, Brigham and Womenʼs Hospital and Harvard Medical School, Boston, MA †Department of Pathology, Medical University of Graz, Austria.
- Am J Surg Pathol. 2008; 32:608-614. Abstract quot
PEComas arising in somatic soft tissue or skin are rare. To further characterize the clinicopathologic spectrum, we herein report a series of 10 primary cutaneous PEComas. Eight patients were female and 2 patients were male. The age at presentation ranged from 15 to 81 years (median, 52 y). None had tuberous sclerosis. Tumor size ranged from 0.7 to 2 cm (median size, 1.5 cm). Eight tumors were located on the limbs and 2 on the back.
The tumors involved the dermis and commonly showed infiltration into the subcutaneous fat. Architecturally, a nested, focally trabecular growth pattern with prominent vasculature composed of delicate thin-walled capillaries was observed. Six tumors were composed of epithelioid cells and 4 showed mixed epithelioid and spindle cell morphology. Tumor cells had clear, palely eosinophilic or granular cytoplasm. Multinucleate tumor giant cells were observed in 3 cases. Mitotic activity ranged from 0 to 2 mitoses per 30 high power fields (mean <1/10 HPF). Pleomorphism or necrosis was absent.
All cases showed at least focal positivity for HMB-45. Melan A was positive in 5/7. In cases where HMB-45 was positive in fewer than 5% of tumor cells (5/10), microphthalmia transcription factor was positive in the majority of the tumor cell nuclei. Desmin positivity was observed in 5 and smooth muscle actin in 1 case, respectively. The other muscle markers (caldesmon, calponin) and also pan-keratin and epithelial membrane antigen were negative. Follow-up data were available in 6 cases and ranged between 3 and 108 months (median, 47 mo). None has recurred to date.
Primary cutaneous PEComas are rare and thus far apparently benign cutaneous tumors. Accurate recognition of this entity is essential because of potential misdiagnosis as malignant tumors, especially malignant melanoma.
- Clear cell 'sugar' tumor (PEComa) of the skin: a case report.
de Saint Aubain Somerhausen N, Gomez Galdon M, Bouffioux B, Courtin C, Theunis A, Vogeleer MN, Myant N.
Institut Jules Bordet, Brussels, Belgium.
J Cutan Pathol. 2005 Jul;32(6):441-4. Abstract quote
The so-called perivascular epithelioid cell neoplasm (PEComa) family includes angiomyolipoma, clear cell 'sugar' tumor (CCST), lymphangioleiomyomatosis, and clear cell myomelanocytic tumor (CCMMT). These rare tumors are characterized by the co-expression of melanocytic and muscle markers. They have been recognized in an increasing number of sites but currently only one case of PEComa, of the CCMMT subtype, has been reported in the skin in abstract form.
We provide the clinicopathologic description of a case of extrapulmonary CCST located in the dermis and superficial subcutis of the thigh of a 60-year-old female. The lesion was composed of nests of epithelioid and spindle cells with abundant clear to granular cytoplasm and distinct cell borders.
The tumor showed strong and diffuse immunoreactivity with HMB-45. Scattered cells expressed desmin and h-caldesmon. Antibodies to S-100 protein, melan-A, cytokeratins, and smooth muscle actin were negative.
This first case of cutaneous PEComa of the CCST type expands the differential diagnosis of clear cell/granular cell tumors of the skin.
Clear cell myomelanocytic tumor of the thigh: report of a unique case.
Folpe AL, McKenney JK, Li Z, Smith SJ, Weiss SW.
Department of Pathology, Emory University, Atlanta, Georgia 30322, USA.
Am J Surg Pathol 2002 Jun;26(6):809-12 Abstract quote
The clear cell myomelanocytic tumor (CCMMT) is a recently reported and very rare member of the perivascular epithelioid cell family of tumors (PEComa). All CCMMTs reported to date have occurred in or immediately adjacent to the falciform ligament/ligamentum teres.
We report a case of CCMMT that occurred in the right thigh of a 43-year-old woman. Histologic examination showed the classic features of CCMMT, and immunohistochemical studies confirmed co-expression of smooth muscle actin, HMB-45, and microphthalmia transcription factor.
Malignant PEComa of the Skull Base.
Department of Pathology, Stanford University Medical Center, Stanford CA.
Am J Surg Pathol. 2004 Sep;28(9):1230-2. Abstract quote
Perivascular epithelioid cell tumors (PEComas) are rare, usually benign lesions comprising a family of neoplasms including angiomyolipoma, lymphangioleiomyomatosis, clear cell "sugar" tumors, and clear cell myomelanocytic tumors.
This report describes an apparent case of a malignant PEComa of the skull base in a 49-year-old woman, a previously undescribed location for this lesion.
- Perivascular Epithelioid Cell Neoplasms of Soft Tissue and Gynecologic Origin: A Clinicopathologic Study of 26 Cases and Review of the Literature.
Folpe AL, Mentzel T, Lehr HA, Fisher C, Balzer BL, Weiss SW.
From the *Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA; daggerDermatopathologische Gemeinschaftspraxis, Friedrichshafen, Germany; double daggerInstitut Universitaire de Pathologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; and section signDepartment of Pathology, Royal Marsden NHS Trust, London, UK.
Am J Surg Pathol. 2005 Dec;29(12):1558-1575. Abstract quote
PEComas, occasionally associated with the tuberous sclerosis complex, are defined by the presence of perivascular epithelioid cells that coexpress muscle and melanocytic markers. This family of tumors includes angiomyolipoma (AML), clear cell sugar tumor of the lung (CCST), lymphangioleiomyomatosis (LAM), and very rare tumors in other locations.
Because non-AML/non-LAM PEComas are extremely rare and their natural history and prognostic features undefined, we present our experience with 26 PEComas of soft tissue and the gynecologic tract, the largest series to date. We also performed a detailed review of the literature, with special attention to features predictive of clinical behavior.
All PEComas exclusive of AML and LAM were retrieved from our consultation files. Immunohistochemistry for pan-cytokeratin (CK), S-100 protein, smooth muscle actins (SMA), desmin, vimentin, HMB45, Melan-A, microphthalmia transcription factor (MiTF), TFE3, CD117, and CD34 was performed. Clinical follow-up information was obtained. Fisher's exact test was performed.
The median patient age was 46 years (range, 15-97 years); there was a marked female predominance (22 females, 4 males). Sites of involvement included the omentum or mesentery (6 cases), uterus (4 cases), pelvic soft tissues (3 cases), abdominal wall (2 cases), uterine cervix (2 cases), and vagina, retroperitoneum, thigh, falciform ligament, scalp, broad ligament, forearm, shoulder, and neck (1 case each). The tumors ranged from 1.6 to 29 cm in size (median, 7.8 cm). Tumors were epithelioid (N = 9), spindled (N = 7), or mixed (N = 10).
Multinucleated giant cells were present in 18 cases. High nuclear grade was noted in 10 cases, high cellularity in 7 cases, necrosis in 8 cases, and vascular invasion in 3 cases. Mitotic activity was 0 to 50 mitotic figures (MF)/50 high power fields (HPF) (median, 0 MF/50 HPF) with atypical MF in 6 cases. IHC results were: SMA (20/25), desmin (8/22), HMB45 (22/24), Melan-A (13/18), MITF (9/18), S-100 protein (8/24), CK (3/23), vimentin (12/14), TFE3 (5/17), c-kit (1/20), and CD34 (0/7).
Clinical follow-up (24 of 26 patients, 92%; median, 30 months; range, 10-84 months) showed 3 local recurrences and 5 distant metastases. At last available clinical follow-up, 2 patients (8%) were dead of disease, 4 patients (17%) were alive with metastatic or unresectable local disease, and 18 patients (75%) were alive with no evidence of disease. No patient in our series had a history of tuberous sclerosis complex. Recurrence and/or metastasis was strongly associated tumor size > median size (8 cm), mitotic activity greater than 1/50 HPF, and necrosis.
We conclude that PEComas of soft tissue and gynecologic origin may be classified as "benign," "of uncertain malignant potential," or "malignant." Small PEComas without any worrisome histologic features are most likely benign. PEComas with nuclear pleomorphism alone ("symplastic") and large PEComas without other worrisome features have uncertain malignant potential. PEComas with two or more worrisome histologic features should be considered malignant. Occasional PEComas express unusual markers, such as S-100 protein, desmin, and rarely CK. The role of TFE3 in PEComas should be further studied.
- Malignant Perivascular Epithelioid Cell Tumour ("PEComa") of Soft Tissue: A Unique Case.
Harris GC, McCulloch TA, Perks G, Fisher C.
From *Canterbury Health Laboratories, Christchurch, New Zealand; daggerNottingham City Hospital, Nottingham, UK; and double daggerRoyal Marsden Hospital, London, UK.
Am J Surg Pathol. 2004 Dec;28(12):1655-1658. Abstract quote
Tumours of perivascular epithelioid cells (PEComas) are being increasingly reported at visceral and somatic sites. Both benign and malignant variants have been identified, although clinical follow-up is often limited, which prevents meaningful predictions of behavior.
We report the case of a malignant soft tissue PEComa with histologically confirmed regional lymph node metastases and radiologically confirmed pulmonary metastases. The light microscopic appearance and immunohistochemical profile (HMB-45, smooth muscle actin positive) and electron microscopic appearance support perivascular epithelioid cell differentiation.
Ann Diagn Pathol. 2005 Oct;9(5):275-8. Abstract quote
Perivascular epithelioid cell tumors are recently characterized neoplasms composed of large clear HMB-45-positive epithelioid cells arranged in an organoid pattern. The histogenesis of these neoplasms remain obscure.
We report here 2 such tumors in young female patients aged 19 and 16 years involving the urinary bladder and vagina, respectively (in the absence of the tuberous sclerosis complex) . Microscopically, both tumors were composed of perivascularly arranged cells with granular eosinophilic fluffy cytoplasm, round-to-oval nuclei, and prominent nucleoli. Melanin pigmentation was present in the vaginal tumor.
Immunohistochemically, both tumors strongly expressed HMB-45. They were negative for cytokeratin, vimentin, and S-100. The vaginal tumor recurred 10 months after resection and chemotherapy. The patient with the bladder tumor was lost to follow-up.
Clear cell myomelanocytic tumor of the urinary bladder.
Pan CC, Yu IT, Yang AH, Chiang H
Am J Surg Pathol 2003 May;27(5):689-92 Abstract quote
Clear cell myomelanocytic tumors are a recently described neoplastic growth considered to be a member of the family of perivascular epithelioid cell tumor. These tumors have a predilection for falciform ligament/ligamentum teres.
We report an additional case arising from the muscularis propria of the urinary bladder in a 33-year-old woman. The tumor consisted of clear to eosinophilic, epithelioid, and spindled cells arranged in fascicles or packets. A delicate vascular stroma was found among the nests. Immunohistochemically, the tumor cells were typically positive for HMB-45 and smooth muscle actin but negative for S-100 protein, Melan-A, desmin, and pan-cytokeratin. The patient has been free of the disease since the excision of the tumor 6 years ago.
This case, in association with the expanding list of perivascular epithelioid cell tumor reported in different sites, suggests that this type of neoplasm may be ubiquitous.
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 smooth muscle tumors of the uterus do not express CD1a: a potential immunohistochemical adjunct in their distinction from uterine perivascular epithelioid cell tumors.
Department of Pathology, Wilford Hall Medical Center, Lackland AFB, San Antonio, TX 78236, USA.
- Ann Diagn Pathol. 2008 Dec;12(6):401-5. Abstract quote
Uterine epithelioid smooth muscle tumors and uterine perivascular epithelioid cell tumors (PEComas) are known to display such a substantial overlap in morphologic and immunophenotypic characteristics that the existence of the latter as a distinct clinicopathologic entity at this location has been called into question.
Recent research suggests that the constituent entities of the PEComa family at all anatomical locations, including lymphangioleiomyomatosis of the uterus, uniformly display immunoreactivity for CD1a. The purpose of this study is to determine the proportion of uterine epithelioid smooth muscle tumors that may similarly be CD1a-positive. Representative sections from 18 archived epithelioid smooth muscle tumors of the uterine corpus (6 epithelioid leiomyosarcomas and 12 epithelioid leiomyomas), diagnosed and classified as such based on World Health Organization criteria, were subjected to immunohistochemical stains for CD1a and HMB-45. The epithelioid component of the tissue sections evaluated ranged from 10% to 100% (mean, 70%). Two cases were composed predominantly of cells with overtly clear cytoplasm. All cases were entirely negative for CD1a. Of 18 cases, 1 (5.5%) (an epithelioid leiomyosarcoma) displayed immunoreactivity for HMB-45 in scattered lesional cells that constituted approximately 5% of the overall tumoral volume for the case. All others were HMB-45-negative.
Given their rarity, future studies are required to confirm that all PEComas of the uterus are indeed uniformly positive for CD1a. However, if the latter staining pattern is confirmed, our findings herein suggest that CD1a may be a useful immunohistochemical adjunct in distinguishing uterine epithelioid smooth muscle tumors from uterine PEComas.
Uterine Epithelioid Leiomyosarcomas With Clear Cells: Reactivity With HMB-45 and the Concept of PEComa
Silva, Elvio G MD*; Deavers, Michael T MD*; Bodurka, Diane C MD†; Malpica, Anais MD*
From the Departments of *Pathology and †Gynecologic Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX.
The American Journal of Surgical Pathology : Volume 28(2) February 2004 pp 244-249 Abstract quote
In this study, we investigated HMB-45 expression in epithelioid uterine leiomyosarcomas with clear cell areas. From 12 epithelioid leiomyosarcomas, we selected 5 that had: 1) clear cell areas and 2) spindle cell areas that were at least focally positive for desmin and caldesmon. The patients' ages ranged from 47 to 82 years (mean 64 years).
Presenting symptoms were uterine bleeding (three), abdominal pain (one), and a pelvic mass (one). There was no history of tuberous sclerosis or lymphangioleiomyomatosis. One patient had stage II disease, one stage III, and three stage IV. All were treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy. Two received radiotherapy, and three were also treated with chemotherapy. The tumors ranged in size from 4 × 3 × 3 cm to 10 × 7 × 6 cm; all had significant cellular atypia, areas of coagulative necrosis, and between 10 and 90 mitoses per 10 high power fields. Vascular invasion was seen in three cases. The epithelioid component varied from 50% to 90% in each case; and the percentage of clear cells was <1% in one case, 5% in one case, and 10% to 80% in three cases. Smooth muscle actin and desmin were positive in all cases. Four cases were positive for HMB-45 only in the clear cell areas. The tumor with <1% of clear cells was negative for HMB-45. All were negative for S-100 and c-kit.
Three patients died of disease at 9, 30, and 32 months; one patient is alive with progressive disease at 6 months, and one patient (stage II disease) is alive with no evidence of disease at 8 months. Unequivocal uterine epithelioid leiomyosarcomas may have clear cells positive for HMB-45.
These tumors might belong to the group of lesion designated as PEComas; however, it is advisable to designate them as uterine leiomyosarcomas. In uterine smooth muscle tumors, some epithelioid cells most likely undergo clear cell changes and become positive for HMB-45. It would be advisable to perform this stain in all epithelioid smooth muscle tumors of the uterus.
Epithelioid lymphangioleiomyomatosis-like tumor of the uterus in a patient without tuberous sclerosis: a lesion mimicking epithelioid leiomyosarcoma
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.
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.
HISTOPATHOLOGY CHARACTERIZATION SCLEROSING
- Sclerosing PEComa: Clinicopathologic Analysis of a Distinctive Variant With a Predilection for the Retroperitoneum.
Department of Pathology, Brigham and Womenʼs Hospital, and Harvard Medical School, Boston, MA.
- Am J Surg Pathol. 2008;32: 493-501 Abstract quote
PEComas (tumors showing perivascular epithelioid cell differentiation) are a family of mesenchymal neoplasms that include angiomyolipoma, clear cell "sugar" tumor of the lung, lymphangiomyomatosis, and a group of uncommon lesions that arise in soft tissue, visceral organs, and skin.
We describe a distinctive variant of PEComa that shows extensive stromal hyalinization, a feature not previously described in these tumors. Thirteen PEComas with extensive stromal hyalinization were identified from a total of 70 cases of PEComa received between 1996 and 2006 (19%). All patients were women, with a mean age of 49 years (range, 34 to 73 y). One patient had tuberous sclerosis. Ten tumors (77%) arose in the retroperitoneum (8 pararenal), and 1 each in the pelvis, uterus, and abdominal wall. Median tumor size was 9.5 cm (range, 4.5 to 28 cm). All except 2 were grossly well-circumscribed. The tumors were composed of cords and trabeculae of cytologically uniform bland epithelioid cells with palely eosinophilic, granular to clear cytoplasm and round nuclei with small nucleoli, embedded in abundant densely sclerotic stroma. Five tumors contained a spindle cell component, and 6 showed focally sheetlike areas. In all cases the tumor cells were focally arranged around blood vessels. All tumors lacked the delicate nesting vascular pattern typical of other PEComas. Mitoses ranged from 0 to 3/50 high-power field (mean 1) in all cases except 1. One tumor showed abrupt transition to areas with strikingly pleomorphic morphology, marked nuclear atypia, frequent mitoses (22/10 high-power field), and fascicular and nested architecture. This was the only case with necrosis. All tumors were immunopositive for desmin (usually diffusely) and HMB-45 (generally in scattered cells); 12/13 (92%) expressed smooth muscle actin, 11/12 (92%) caldesmon, 11/12 (92%) microphthalmia transcription factor (D5), and 3/13 (23%) melan-A. Only 1 (8%) was focally S-100 positive. All tumors were negative for epithelial membrane antigen, PAN-K, and KIT (CD117). Follow-up was available for 9 patients, ranging from 10 to 64 months (median, 33). One patient (whose tumor showed transition to high-grade malignant morphology) developed metastases to lung, liver, and abdominal wall. No other tumor has recurred or metastasized thus far. Sclerosing PEComa is a distinctive variant with a predilection for the pararenal retroperitoneum of middle-aged women.
Sclerosing PEComas seem to pursue an indolent clinical course, unless associated with a frankly malignant component. Long-term follow-up will be required to confirm these findings.
CHARACTERIZATION POSITIVE HMB-45
ADDITIONAL STAINS CD1a
- CD1a expression in PEComas.
Division of Molecular Pathology, Department of Microbiology and Pathology, Tottori University, Yonago, Japan.
- Pathol Int. 2008 Mar;58(3):169-73. Abstract quote
According to the World Health Organization classification, neoplasms with perivascular epithelioid cell differentiation (PEComas) are mesenchymal tumors composed of histologically and immunohistochemically distinctive PEC. Generally, nearly all PEComas have immunoreactivity for both melanocytic (HMB-45 and/or melan A) and smooth muscle (actin (SMA) and/or desmin) markers. Recently the authors reported that benign clear cell sugar tumor of the lung, one of the PEComas, expressed CD1a.
Therefore the purpose of the present study was to investigate the relationship between PEComas and CD1a expression. Nineteen PEComas were obtained, which included angiomyolipoma of the kidney or liver, lymphangiomyomatosis of the uterus or lung and clear cell sugar tumor of the lung. Eighteen tumors had alpha-SMA and HMB-45 expression and 16 had melan A expression. In contrast, all 19 tumors had CD1a expression. The present study confirms CD1a expression in many cases of PEComa.
These data suggest that CD1a expression can be an additional new marker for PEComas and also supports the distinct and integrated disease entity of PEComas.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES DDCCMN (ATYPICAL DISTINCTIVE DERMAL CLEAR CELL MESENCHYMAL NEOPLASM)
- Atypical distinctive dermal clear cell mesenchymal neoplasm arising in the scalp.
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
- J Cutan Pathol. 2008 Apr;35(4):423-7. Abstract quote
Distinctive dermal clear cell mesenchymal neoplasm (DDCCMN) is a newly described entity characterized by a dermal proliferation of neoplastic cells with clear to reticulated cytoplasm and vesicular nuclei.
Atypical features in the form of nuclear pleomorphism and mitoses may be found. The histogenesis of these neoplastic clear cells is not currently known but they are thought to be mesenchymal in origin. Immunohistochemically, they stain positively for NKI-C3 and negatively for melanocytic, epithelial and lymphoid markers. All five cases originally reported by Lazar and Fletcher occurred in the lower extremities.
We report herein a case of DDCCMN with atypical features arising in the scalp.
- Distinctive dermal clear cell mesenchymal neoplasm: clinicopathologic analysis of five cases.
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
- Am J Dermatopathol. 2004 Aug;26(4):273-9. Abstract quote
Dermal clear cell tumors are not common. This group of lesions is comprised primarily of clear cell adnexal lesions, balloon cell melanocytic lesions, and metastatic clear cell carcinomas.
We report the clinicopathologic features of five cases of a novel dermal clear cell neoplasm that appears mesenchymal in nature. The affected patients included 3 men and 2 women ranging in age from 38 to 70 (median, 45 years). All the lesions occurred on the lower limb. Clinically described as smooth cutaneous nodules, size ranged from 0.5 to 2.5 cm in greatest dimension and the lesions were present from weeks to 5 years prior to excision. Situated in the reticular dermis, the tumors usually extended to involve the subcutis with sparing of the papillary dermis.
The tumors were composed of large optically clear cells with vesicular nuclei. The lesions entrapped adnexal structures and thin dermal collagen fibers. Mitoses were rare (less than 1 per 25 hpf). A single case showed more pleomorphic nuclei as well as quite frequent mitoses and was considered of uncertain biologic potential. Immunohistochemistry revealed reactivity only for NKI-C3 (5/5 cases), CD68 (2/5 cases), and vimentin (2/3 cases); melanocytic, epithelial, and lymphoid markers were uniformly negative.
All five lesions were locally excised; the more pleomorphic and mitotically active lesion was widely re-excised and given subsequent radiation therapy. In follow-up ranging from 1.5 to 11 years (median, 5.5 years), none of these lesions has recurred. These tumors appear to be mesenchymal in nature, but their precise line of differentiation is unknown.
Recognition of these lesions is important to avoid confusion with better-known malignant neoplasms.
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Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
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