Benign clear (sugar) cell tumor of the lung with CD1a expression

Reported herein is a case of benign clear cell tumor of the lung in a 60-year-old man. Chest X-ray and CT examination revealed an abnormal nodule with homogenous density and a clear margin in the lower lobe of the left lung. The resected tumor was 13 mm in size, well-circumscribed and was graysh-white on cut surface. Histological examination showed a diffuse growth pattern of polygonal tumor cells with indented and pleomorphic nuclei, and clear abundant cytoplasm with a distinct cell border surrounded by thin-walled vascular spaces and sinusoid-type vessels. The clear cytoplasm contained numerous glycogen granules as demonstrated by PAS staining. In the present case there was focal immunoreactivity for S-100 protein, HMB-45, neuron-specific enolase, cathepsin B and melan A, which are consistent with reported immunohistochemical staining patterns of benign clear cell tumor. Based on these findings, the tumor was diagnosed as a benign clear cell tumor of the lung. Although most clear cell tumors are considered to belong to the family of neoplasms with perivascular epithelioid cell differentiation (PEComas), histogenesis of benign clear cell tumor of the lung has remained unclear. This first report of CD1a expression in this tumor might provide a new insight into its histogenesis and diagnosis.     

Epithelioid smooth muscle tumors of the uterus do not express CD1a: a potential immunohistochemical adjunct in their distinction from uterine perivascular epithelioid cell tumors

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.     

血管周上皮样细胞肿瘤的分子遗传学

血管周上皮样细胞肿瘤(perivascular epithelioid cell tumours,PEComas)是由组织学和免疫组织化学上有独特表现的血管周上皮样细胞构成的间叶性肿瘤,PEComas家族包括肾血管平滑肌脂肪瘤、肺透明细胞"糖"瘤、淋巴管肌瘤病、淋巴管平滑肌瘤、镰状韧带透明细胞肌黑色素细胞性肿瘤和其他部...     

C-Kit-positive metastatic malignant pigmented clear-cell epithelioid tumor arising from the kidney in a child without tuberous sclerosis

We report the first pediatric case of malignant pigmented epithelioid clear-cell tumor arising from kidney; the lesion occurred in a 12-year-old girl without tuberous sclerosis. The tumor was widely metastatic to the retroperitoneum and chest, and the patient died of the disease 9 months after diagnosis, despite active chemotherapy. Pigmented epithelioid clear-cell tumor of the kidney is a rare variant of epithelioid angiomyolipoma and a member of the family of perivascular epithelioid cell tumors (PEComas). The tumor demonstrated overlapping features between clear-cell sugar tumor and epithelioid variant of angiomyolipoma. Tumor cells were positive for HMB-45 expression, negative for any evidence of muscular differentiation, and contained melanin pigment and premelanosomes in the cytoplasm. Diffuse C-Kit (CD117) positivity was identified throughout the tumor. This is the first report of C-Kit–positive malignant PEComas.     

PEComa: what do we know so far?

PEComas (tumours showing perivascular epithelioid cell differentiation) are a family of related mesenchymal neoplasms that include angiomyolipoma, lymphangiomyomatosis, clear cell "sugar" tumour of the lung, and a group of rare, morphologically and immunophenotypically similar lesions arising at a variety of visceral and soft tissue sites. These tumours all share a distinctive cell type, the perivascular epithelioid cell or "PEC' (which has no known normal tissue counterpart). PEComas show a marked female predominance and are composed of nests and sheets of usually epithelioid but occasionally spindled cells with clear to granular eosinophilic cytoplasm and a focal association with blood vessel walls. PEComas appear to arise most commonly at visceral (especially gastrointestinal and uterine), retroperitoneal, and abdominopelvic sites, with a subset occurring in somatic soft tissue and skin. Nearly all PEComas show immunoreactivity for both melanocytic (HMB-45 and/or melan-A) and smooth muscle (actin and/or desmin) markers. A subset of PEComas behave in a malignant fashion. This review examines the members of the PEComa family, with an emphasis on lesions arising outside of the kidney, lung and liver, and discusses preliminary evidence for pathological features that might predict malignant behaviour.     

Malignant neoplasm of perivascular epithelioid cells of the liver

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.     

Expression of CD44 and CD29 by PEComa cells suggests their possible origin of mesenchymal stem cells

Background: Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor composed of histologically and immunohistochemically distinctive perivascular epithelioid cells. The perivascular epithelioid cell (PEC) co-expresses melanocytic and muscle markers. Since no normal counterpart to the PEC has ever been identified in any normal tissue, the cell origin of these tumors is still uncertain. Although, several hypotheses have recently been advanced to explain the histogenesis of PEComa, it remains unclear. Methods: The aim of this study was to discuss whether differential expression of stem cell-associated proteins could be used to aid in determining the histogenesis of PEComa. For this purpose, we detected the immunoexpression of 5 kinds of stem cell markers on PEComas, including CD29, CD44, CD133, ALDH1, and nestin. In addition to observed histopathologic morphology, we also performed PEComa relevant clinical diagnostic markers (HMB-45, SMA, melan-A, Desmin, Ki-67, S-100 and TFE3) to identify whether they belonged to PEComas. Results: Our study included 13 PEComa samples, and we obtained positive immunoexpression results as follows: CD29 (13/13), CD44 (8/13), ALDH1 (10/13), nestin (1/13), and CD133 (0/13). Conclusions: Since CD44 and CD29 are surface proteins associated with MSCs, these results suggest that PEComa might arise from MSCs. However, whether MSCs are the origin of PEComa needs to be further explored in the future.     

Renal angiomyolipoma, fat-poor variant—a clinicopathologic mimicker of malignancy

Angiomyolipomas, composed of thick-walled blood vessels, smooth muscle, and adipose tissue, belong to the perivascular epithelioid cell neoplasms (PEComas), a family of tumors believed to be derived from perivascular epithelioid cells which co-express smooth muscle and melanocytic markers. Although most angiomyolipomas are benign, a subset of PEComas has metastatic potential. The pathologic and clinical spectrum of these tumors continues to evolve. We sought to evaluate a subset of renal angiomyolipomas with a minimal amount of fat. We studied 48 renal angiomyolipomas in 41 patients (33 females and 8 males). Based on the amount of adipose tissue, the lesions were categorized as fat-poor, fat-average, and fat-rich lesions (<25, 25–75, and >75 % of fat, respectively). Stains for smooth muscle actin, calponin, HMB-45, melanocyte-associated antigen PNL2, estrogen, and progesterone receptor were examined. Four patients (all females) had more than one lesion, four had coexistent uterine leiomyomata, two had coexistent renomedullary interstitial tumor, and males had only single lesions. Except for one woman, all lesions were sporadic. Twenty-nine were fat-poor (60 %) lesions; 8, fat-average (17 %) lesions; and 11, fat-rich (23 %) lesions. The fat content did not correlate with tumor size: the largest fat-poor and smallest fat-rich lesions were >6 and <2 cm, respectively. All lesions stained with smooth muscle actin and HMB-45; 41 % of tumors were positive for estrogen receptor (11 females and 1 male). No patient had metastases (follow-up 2–11 years). In our series, fat content in angiomyolipoma was not associated with tumor size. Fat-poor angiomyolipomas affected predominantly women and were morphologically and radiologically distinct as mimickers of malignancy. Whether they are biologically different from conventional tumors requires further studies.     

An immunohistochemical study of benign clear cell ('sugar') tumor of the lung

Benign clear cell ("sugar") tumor is a rare and most unusual pulmonary neoplasm. Although several reports in the literature have focused on the ultrastructural features of benign clear cell tumor, only a few cases have been formally studied by immunochemistry. Using a broad panel of polyclonal and monoclonal antibodies, five cases were evaluated. In all five cases, there was diffuse immunoreactivity for cathepsin B. Four cases showed immunoreactivity for HMB-45 and for alpha 1-antitrypsin. By two different sources for antivimentin, there was immunoreactivity in four cases (Biogenex, Dublin, Calif) and in two cases (DAKO, Santa Barbara, Calif), respectively. Additional immunoreactivity was present for S100 protein (three cases), HAM-56 (two cases), factor XIIIA (two cases), and neuron-specific enolase (one case). No case expressed immunoreactivity for keratin (AE 1, AE 3, or CAM 5.2), carcinoembryonic antigen, chromogranin, synaptophysin, glial fibrillary acidic protein, or alpha 1-antichymotrypsin. This immunochemical profile suggests that HMB-45, in combination with a variety of immunostains, may serve to distinguish benign clear cell tumor from other clear cell neoplasms.     

Clear cell sarcoma. An immunohistochemical and ultrastructural study

The histogenesis of clear cell sarcoma was investigated by immunohistochemical examination of five tumors (two melanotic and three amelanotic) and electron microscopic examination of two of these tumors (one melanotic and one amelanotic). Melanin production was observed histologically in two of the tumors. The cytoplasm of cells in both types of tumor contained various numbers of melanosomes. Melanoma-specific antibody (HMB-45), anti-S-100 protein, and anti-vimentin antibodies gave positive reactions in four tumors, while all tumors showed Leu-7 immunoreactivity. No cytokeratin or epithelial membrane antigen (EMA) was detected immunohistochemically in any tumor. The immunoreactivity of this type of tumor with HMB-45 antibody strongly suggests melanocytic differentiation rather than schwannian or synovial differentiation. The reaction of the cells of one tumor with only Leu-7 indicates the existence of undifferentiated clear cell sarcoma of neuroectodermal origin that does not show definite melanocytic differentiation.     

Clear Cell Sarcoma. An Immunohistochemical and Ultrastructural Study

The histogenesis of clear cell sarcoma was investigated by immunohistochemical examination of five tumors (two melanotic and three amelanotic) and electron microscopic examination of two of these tumors (one melanotic and one amelanotic). Melanin production was observed histologically in two of the tumors. The cytoplasm of ceils in both types of tumor contained various numbers of melanosomes. Melanoma-specific antibody (HMB-45), anti S 100 protein, and anti vimentin antibodies gave positive reactions in four tumors, while all tumors showed Leu 7 immunoreactivity. No cytokeratin or epithelial membrane antigen (EMA) was detected immunohisto-chemically in any tumor. The immunoreactivity of this type of tumor with HMB-45 antibody strongly suggests melanocytic differentiation rather than schwannian or synovial differentiation. The reaction of the cells of one tumor with only Leu-7 indicates the existence of undifferentiated clear cell sarcoma of neuroectodermal origin that does not show definite melanocytic differentiation. Acta Pathol Jpn 39: 321 327, 1989.     

Perivascular epithelioid cell tumor (PEComa) of the liver: a case report and review of the literature

Perivascular epithelioid cell tumor (PEComa) is rare entity and has been described only recently. By immunohistochemistry and genetics it belongs to the family of tumours which comprises angiomyolipoma, clear cell "sugar" tumor of lung, lymphangioleiomyomatosis and clear cell myomelanotic tumor of ligamentum falciforme/teres hepatis. We describe an unusual case of hepatic PEComa arising in a 55-year-old woman with previous history of glioblastoma. Histologically the tumor grew in expansive way, and was composed of clear and eosinophilic epithelioid cels, without vascular or lipomatous component characteristic of angiomyolipoma. There was mild nuclear pleomorphism, sporadic mitotic activity and haemorrhage without necrosis. On immunohistochemistry, the tumor was HMB-45+50, Melan-A and smooth muscle actin positive. Tyrosinase, S-100 protein, cytokeratin coctail, EMA, vimentin, muscle specific actin, CD10, TTF-1, hepatocyte, desmin and cyclin D1 were negative. Sporadic nuclear p53 positivity was seen. The main differential diagnosis of hepatic PEComa includes clear cell variant of liver cell adenoma and hepatocellular carcinoma, metastases of various clear cell carcinomas and metastasis of malignant melanoma. In respect of uncertain biologic potential of PEComa, long term follow up is indicated.     

Immunohistochemical and ultrastructural investigation on cutaneous neuroendocrine carcinoma: report of a case and review of the literature

We report a tumor in an 80-year-old man that was difficult to distinguish from other tumors, i.e., small cell carcinoma of the lung, PNET/Ewing tumor, malignant lymphoma, or malignant melanoma (amelanotic), and which was finally identified as cutaneous neuroendocrine carcinoma using immunohistochemical and ultrastructural methods. Autopsy did not show any tumors in the lungs, excluding the possibility of small cell carcinoma of the lung. Immunohistochemistry tests gave negative results for LCA, UCHL-1, CD3, and CD20, thereby excluding malignant lymphoma, and the negative results for S-100 protein and HMB-45 ruled out malignant melanoma. The possibility of PNET/Ewing sarcoma was also excluded because of negativity for CD99. In addition, the ultramicrostructure showed intercellular junctional complexes and neuroendocrine granules, indicating that the tumor had characteristics of both epithelial and neuroendocrine tissues. We therefore diagnosed the primary carcinoma of the skin as cutaneous neuroendocrine carcinoma.     

Incidental perivascular epithelioid cell tumor in an inguinal hernia sac

Perivascular epithelioid tumors (PEComa) are uncommon mesenchymal neoplasms demonstrating positivity for muscular and melanocytic immuno-markers. Included in this category are angiomyolipoma, lymphangioleiomyomatosis, and clear cell sugar tumors. Lesions which do not fit into these categories are classified as “not otherwise specified”. We present a case of an incidentally discovered PEComa within inguinal hernia sac contents in a 70-year-old woman. It consisted of spindled and epithelioid cells with bland oval nuclei, small nucleoli and clear to light eosinophilic cytoplasm. There was no atypia or mitoses. The lesion was strongly positive for HMB45 and smooth muscle actin. Pelvic soft tissue and peritoneal PEComas are rarely reported in literature and very little is known about their prognosis. We discuss the immunohistochemistry, differential diagnosis, and pathogenesis of PEComas.