mart-1-antigen and Angiomyolipoma

Angiomyolipoma is a benign mesenchymal tumor composed of variable amounts of smooth muscle, adipose tissue and thick-walled blood vessels, and usually named PEComas (perivascular epithelioid cell tumors). PEComas share overlapping histopathological features with epithelioid cells along a perivascular distribution and characteristic immunohistochemistry with coexpression of myoid and melanocytic markers (HMB-45 /or Melan-A). We report the first case of primary orbital angiomyolipoma with negative melanocytic marker.. An 80-year-old Asian woman had a 2-year history of progressive swelling in the left upper eyelid. External examination revealed 3 cm of relative proptosis of the left eye and a palpable mass in the left superonasal orbit. Computed tomographic scan demonstrated a circumscribed, heterogeneous orbital mass. Excision biopsy was done and the histological finding demonstrated the orbital mass was composed of mature adipocytes, intermingled with spindle or oval-shaped cells, and accompanied by thick-walled blood vessels. Immunohistochemically, tumor cells were positive for CD34 and HHF-35, but negative for cytokeratin, HMB-45 and Melan-A. The diagnosis of angiomyolipoma was made. No recurrence was noted at 2-year follow-up.. In our case, the HMB-45 negativity may be explained by the rarity of the epithelioid cells, and the HMB-45 positivity is often weaker or absent in spindle cells. Angiomyolipoma, although rare, should be added to the differential diagnosis of space-occupying orbital lesion.

Topics: Aged, 80 and over; Angiomyolipoma; Antigens, CD34; Biomarkers, Tumor; Biopsy; gp100 Melanoma Antigen; Humans; Immunohistochemistry; MART-1 Antigen; Melanoma-Specific Antigens; Orbital Neoplasms; Tomography, X-Ray Computed

Extrarenal retroperitoneal angiomyolipomas are rare.. To review the literature.. Angiomyolipomas, previously classified as hamartomas, are now classified as benign tumours. Thirty cases of primary retroperitoneal angiomyolipomas have been reported. Diagnosis of the disease upon is based radiological and pathological findings of triphasic features of (a) fat and (b) blood vessels and myoid tissue. Immunohistochemistry tends to be positive for HMB45, MART1, HHF35, calponin, NKI-C3, and CD117. The lesion is common in women. Treatment options have included the following: (a) radical surgical excision of the lesion with renal sparing surgery or radical nephrectomy in cases where malignant tumours could not be excluded and (b) selective embolization of the lesion alone or prior to surgical excision. One case of retroperitoneal angiomyolipoma was reported in a patient 15 years after undergoing radical nephrectomy for angiomyolipoma of kidney and two cases of distant metastases of angiomyolipoma have been reported following radical resection of the tumour.. With the report of two cases of metastases ensuing surgical resection of the primary lesions there is need for academic pathologists to debate and review angiomyolipomas to decide whether to reclassify angiomyolipomas as slow-growing malignant tumours or whether the reported cases of metastases were de novo tumours or metastatic lesions.

Topics: Actins; Adult; Aged; Aged, 80 and over; Angiomyolipoma; Biomarkers, Tumor; Calcium-Binding Proteins; Calponins; Diagnosis, Differential; Embolization, Therapeutic; Female; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Kidney Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Microfilament Proteins; Middle Aged; Nephrectomy; Rare Diseases; Retroperitoneal Neoplasms; Sex Factors; Treatment Outcome

Hepatic angiomyolipoma is a rare, benign, hepatic mesenchymal neoplasm found in both males and females, and most commonly in adult females. Angiomyolipoma occurs most commonly in the kidneys. The liver represents the second most frequent site of involvement. Hepatic angiomyolipomas are composed of varying amounts of smooth muscle cells, adipose tissue, and vessels. The smooth muscle cell component is the most specific to the diagnosis. The smooth muscle cells can have varying morphologies and are positive for homatropine methylbromide-45 but are negative for hepatocyte paraffin 1 and S100 protein. The definitive diagnostic study remains the histologic examination of the surgically resected lesion coupled with immunohistochemical stains. The differential diagnosis includes hepatocellular carcinoma, hepatic adenoma, leiomyoma, hepatoblastoma, melanoma, and gastrointestinal stromal tumor. The immunohistochemical staining pattern differentiates this lesion from other malignant and benign liver lesions. If the diagnosis of hepatic angiomyolipoma has been made, it can be followed conservatively or surgically resected.

Topics: Angiomyolipoma; Antigens, Neoplasm; Female; Humans; Liver Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Neoplasm Proteins; S100 Proteins

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.

Topics: Actins; Angiomyolipoma; Antigens, Neoplasm; Epithelioid Cells; Humans; Immunohistochemistry; MART-1 Antigen; Melanoma-Specific Antigens; Muscle, Smooth; Neoplasm Proteins

Melan-A/MART-1 is a recently identified new melanocytic differentiation marker, which is recognized as an antigen on melanoma cells by cytotoxic T-lymphocytes. It is of interest for clinicians as potential immunotherapeutic target and it is relevant for pathologists as a novel diagnostic marker, since two antibodies (A103 and M2-7C10) have become available to study Melan-A/MART-1 expression on archival material. Both antibodies are useful in the differential diagnosis of melanocytic tumors, especially metastatic tumors, since they are more sensitive than HMB-45. Both antibodies are also of diagnostic value in the recognition of perivascular epithelioid cell tumors (angiomyolipoma, lymphangioleiomyomatosis, and clear cell tumor). Since A103 has the unique property of staining many steroid hormone producing cells, this antibody is also of value for the recognition of tumors derived from these cells, such as adrenocortical carcinomas. Both antibodies are likely to be included in the routine diagnostic armamentarium of many immunohistochemical laboratories in the near future.

Topics: Adrenal Cortex Neoplasms; Angiomyolipoma; Antibodies, Monoclonal; Antigens, Differentiation; Antigens, Neoplasm; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Lymphangioleiomyomatosis; Lymphatic Metastasis; Male; MART-1 Antigen; Melanocytes; Melanoma; Neoplasm Proteins; Ovarian Neoplasms; Skin Neoplasms; Testicular Neoplasms

The renal angiomyolipoma (AML) is a benign tumor characteristically composed of fat, smooth muscle tissue, and vessels. We collected AMLs from our nephrectomy database, reclassified them according to their histological appearance, recorded the demographic, clinical, and pathological parameters, and compared them with oncocytoma (RO) and renal cell carcinoma (RCC). Immunohistochemistry was ordered in 41 cases. In 2224 nephrectomies, we found 52 AMLs with a 53 mm median size. The mean age was 52.76. Forty-eight tumors were sporadic, while four were hereditary. The revision resulted in 31 classic, 13 leiomyoma-like, five lipoma-like, two epithelioid, and one AML with epithelial cysts. SMA was diffusely positive, except for the epithelioid type, while MelanA harbored stronger expression than HMB45. AML was more frequent in females and appeared ten and 7 years earlier than RO and RCC, respectively. The follow-up time was 7.42 years, and neither tumor-related death nor relapse occurred. AML is rare in nephrectomies and develops primarily in females in their 50s with an average size of 50-60 mm at the surgery. The histological appearance in order of frequency is classic, leiomyoma-like, lipoma-like, epithelioid, and cystic. The MelanA, HMB45, and SMA immunohistochemistry can support the light-microscopic findings.

Topics: Angiomyolipoma; Antibodies, Monoclonal; Carcinoma, Renal Cell; Female; Hamartoma; Humans; Kidney; Kidney Neoplasms; Leiomyoma; Lipoma; MART-1 Antigen; Middle Aged

BACKGROUND Microscopic tumor foci have been detected incidentally on renal biopsy, including renal cell carcinoma and renomedullary interstitial cell tumor (medullary fibroma). A report is presented of a case of an incidental finding of microscopic renal angiomyolipoma that was diagnosed and completely excised on core needle biopsy. CASE REPORT A 44-year-old woman was referred to our hospital for evaluation of persistent mild proteinuria. Three years previously, she was diagnosed with Cushing's syndrome associated with a right adrenal cortical adenoma, which was successfully treated with unilateral adrenalectomy. At the time of surgery, abdominal computed tomography (CT) showed no renal lesions. During the present admission, a renal biopsy was performed that showed minimal changes in the renal glomeruli and interstitium. Immunofluorescence showed weakly positive staining for IgM in the glomeruli and no dense deposits. A microscopic focus of a predominantly spindle-cell tumor was found in the corticomedullary region. Immunohistochemistry showed positive immunostaining for HMB-45, Melan-A, and alpha-smooth muscle actin (ASMA), which supported a diagnosis of angiomyolipoma. Abdominal ultrasound at one-year follow-up showed no evidence of residual renal tumor. CONCLUSIONS To our knowledge, this is the first reported case of a completely excised incidental microscopic renal angiomyolipoma. This case demonstrated that even when imaging findings are normal, renal biopsy may detect microscopic foci of primary renal tumors.

Topics: Actins; Adult; Angiomyolipoma; Biomarkers, Tumor; Biopsy, Large-Core Needle; Female; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Incidental Findings; Kidney Neoplasms; MART-1 Antigen; Melanoma-Specific Antigens

It is well known to pathologists that melanoma is "the great mimicker," looking like almost any other tumor, and able to metastasize anywhere in the body. We report a case of a 48-year-old female with a history of metastatic melanoma 4 years before, who presented with a hepatic mass. Microscopic examination of the liver mass revealed sheets of pleomorphic, epithelioid cells, which expressed a pan-melanocytic cocktail (MART1, HMB45, and tyrosinase). These findings were initially interpreted as metastatic melanoma and the case was transferred for dermatopathology consultation. We compared the morphology of this tumor to the primary melanoma and noticed that the primary melanoma showed nevoid cytology, morphologically distinct from the liver lesion. Consequently, we performed additional immunohistochemical studies, which determined that the liver mass was negative for S100 and SOX10, and established a final diagnosis of epithelioid angiomyolipoma. The key for reaching the correct diagnosis was the morphologic comparison with the original lesion and the evaluation of a wider immunohistochemical profile. For appropriate management in patients with new lesions, even in the context of a patient with known metastatic disease, it is essential to consider other neoplasms in the differential diagnosis.

Topics: Angiomyolipoma; Diagnosis, Differential; Epithelioid Cells; Female; gp100 Melanoma Antigen; Humans; Liver Neoplasms; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Middle Aged; Monophenol Monooxygenase; Skin Neoplasms

Hepatic angiomyolipoma (HAML) is a rare and difficult-to-diagnose liver tumour. The aim of this study was to summarize experiences in the management of HAML and to recommend a practical treatment strategy.. We retrospectively studied 92 patients who were diagnosed with HAML and analysed the clinical presentation, histopathological features and treatment of the tumours encountered at our institute from May 2009 to June 2016.. The patients included 67 females and 25 males who underwent at least one radiographic examination. Sixty-eight patients underwent radical hepatectomy, two patients underwent liver biopsy, and 22 patients were treated with radiofrequency ablation after liver biopsy. The tumour cells correspondingly expressed both melanoma cell markers (HMB45, MART-1) and smooth muscle cell markers. Two patients were found to have tumour recurrence (2/92, 2.2%) after radical hepatectomy, and none of the patients died.. Diagnosis of HAML depends on pathological findings. The treatment strategy for HAML should be selected according to the tumour size, liver biopsy, location and clinical symptoms of HAML. Patients should be followed closely after surgery because of the malignant potential of HAML.

Topics: Adult; Aged; Angiomyolipoma; Biopsy; China; Female; gp100 Melanoma Antigen; Hepatectomy; Humans; Liver; Liver Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Neoplasm Recurrence, Local; Radiofrequency Ablation; Retrospective Studies

Epithelioid angiomyolipoma (EAML) of liver is a rare neoplasm. Hepatic EAML is often misdiagnosed as other neoplasms such as hepatocellular carcinoma due to non-specific clinical and radiologic features. The morphologic features under microscope and immunohistochemistry staining profile are important in the diagnosis EAML. Here, we report a case of 52-year-old man who found 1.2 cm mass in liver by routine checkup. On the impression of hepatocellular carcinoma, lateral sectionectomy of the liver was done. Microscopically, the tumor is composed of predominant epithelioid cells with vascular component and foamy cells. These cells were positive for HMB45, MelanA, and smooth muscle actin and negative for epithelial membrane antigen. The final diagnosis was hepatic EAML.

Topics: Angiomyolipoma; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Liver; Liver Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Microscopy, Fluorescence; Middle Aged; Tomography, X-Ray Computed

Angiomyolipoma with epithelial cysts (AMLEC) is a distinctive variant of angiomyolipoma characterized by grossly apparent epithelial cysts and a cellular, müllerian-like subepithelial stroma. Some authors suspect that the epithelial cysts mainly represent dilated entrapped native renal collecting duct epithelium, while other authors think that they represented true epithelial differentiation of the AML. Recently, it has been reported that obvious immunolabeling of melanocytic markers such as Melan A and HMB45, which are often immunolabeled in classical angiomyolipoma, are present in epithelial cysts in cases of AMLEC. Here, we report the case of a 43-year-old Japanese woman with AMLEC, and attempt to elucidate the significance of melanocytic marker immunolabeling in the cyst's epithelium. In the present case, Melan A was labeled in the cyst's epithelium, and was thought to reflect its labeling in renal tubules existing in the renal parenchyma outside the tumor. This finding may indicate that the cyst epithelium is derived from entrapped renal tubules inside the AML. Non-immunolabeling of the estrogen and progesterone receptors in the cyst epithelium may also suggest that the cyst epithelium is not neoplastic, in contrast to their labeling in neoplastic cells existing in cyst wall. Further examination, such as molecular analysis, is needed to determine whether these epithelial cysts is neoplastic or non-neoplastic.

Topics: Adult; Angiomyolipoma; Biomarkers, Tumor; Cysts; Epithelium; Female; Humans; Immunohistochemistry; Kidney Neoplasms; Kidney Tubules; MART-1 Antigen

Topics: Adult; Angiomyolipoma; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Diagnosis, Differential; Female; gp100 Melanoma Antigen; Humans; Kidney Neoplasms; Liver Neoplasms; MART-1 Antigen; Melanoma-Specific Antigens; Neoplasms, Multiple Primary; Tomography, X-Ray Computed; Tuberous Sclerosis; Young Adult

To study the clinicopathologic features, immunophenotype, histological diagnosis and prognosis of hepatic epithelioid angiomyolipoma.. Clinical data of 25 cases of hepatic epithelioid angiomyolipoma were collected along with follow-up study of the patients. The pathological features were documented and immunohistochemical study of various markers was performed with an emphasis on diagnosis and differential diagnosis.. Hepatic epithelioid angiomyolipoma was more commonly found in young women without characteristic clinical symptoms. Its morphological features were characterized by marked cytological atypia, relatively rare mitotic figures; radial distribution of tumor cells around the thin-walled blood vessels or muscular vessels; and the presence of common multinucleated giant cells and large ganglion-like tumor cells. The tumor cells expressed both melanoma cell markers (HMB45, MART-1) and smooth muscle cell markers (SMA). Tumor cells expressed various other markers including ER 16% (4/25), PR 32% (8/25), TFE3 24% (6/25) and p53 60% (15/25).. Hepatic epithelioid angiomyolipoma has variable morphological features and characteristic immunohistochemical phenotype. The differential diagnoses include a variety of tumors. The biological behavior of the tumor tends to be benign.

Topics: Age Factors; Angiomyolipoma; Biomarkers, Tumor; Diagnosis, Differential; Female; Follow-Up Studies; Gastrointestinal Neoplasms; Giant Cells; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Immunophenotyping; Liver Neoplasms; MART-1 Antigen; Melanoma-Specific Antigens; Muscle, Smooth; Prognosis

To study the clinicopathologic features, immunophenotype and genetic changes of perivascular epithelioid cell neoplasms (PEComa).. A total of 25 cases of PEComa located in various anatomic sites were selected for immunohistochemical staining (SP or EnVision method). TFE3 fluorescence in-situ hybridization was also performed to determine the TFE3 gene status.. The age of patient ranged from 21 to 61 years (mean = 43 years). The male-to-female ratio was 1: 1.3. Histologically, 22 cases represented conventional angiomyolipomas, composed of a mixture of adipose tissue, spindle element, epithelioid smooth muscle cells and abnormal thick-walled blood vessels in various proportions. Three cases involving lung, soft tissue and broad ligament had subtle but distinctive morphologic features. Nested or sheet-like architecture with epithelioid or spindle cells was observed. Immunohistochemical study showed that HMB 45, melan A, smooth muscle actin and cathepsin K were expressed in 80% (20/25), 88% (22/25), 88% (22/25) and 100% (25/25) of PEComa, respectively. Within positive cases, the average proportion of positive tumor cells was 36%, 41%, 35% and 90% respectively for HMB 45, melan A, smooth muscle actin and cathepsin K. TFE3 was negative in all of the 22 renal and hepatic PEComa studied, while it was positive in the 3 cases of extra-hepatorenal PEComa. None of the 25 cases exhibited evidence of TFE3 gene fusion or amplification.. Extra-hepatorenal PEComa have distinctive morphologic features and are associated with TFE3 overexpression. Cathepsin K immunostaining demonstrates high sensitivity and specificity in PEComa, better than other commonly employed immunomarkers. This marker is thus useful in diagnosis of PEComa and distinction with other neoplasms.

Topics: Actins; Adult; Angiomyolipoma; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Cathepsin K; Female; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Kidney Neoplasms; Liver Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Perivascular Epithelioid Cell Neoplasms; Young Adult

Two cases of epithelioid angiomyolipoma of the kidney are reported. A 62-year-old female with incidental left renal tumor underwent laparoscopic leftpartial nephrectomy under a diagnosis of renal cell carcinoma. A pathological examination revealed epithelioid angiomyolipoma. The second case was that of a 35-year-old female with back pain. A laparoscopic right nephrectomy revealed epithelioid angiomyolipoma. This recently identified variant of angiomyolipoma is sometimes associated with aggressive clinical behavior including local recurrence and metastasis.

Topics: Adult; Angiomyolipoma; Biomarkers, Tumor; Diagnosis, Differential; Female; gp100 Melanoma Antigen; Humans; Kidney Neoplasms; Laparoscopy; Magnetic Resonance Imaging; MART-1 Antigen; Melanoma-Specific Antigens; Nephrectomy; Tomography, X-Ray Computed; Treatment Outcome

Epithelioid angiomyolipomas (AMLs) of the liver are rare tumors with imaging and cytologic features overlapping with those of hepatocellular carcinomas. We report the fine needle aspiration and core biopsy findings of an epithelioid AML in the right hepatic lobe of a 32-year-old female with tuberous sclerosis. She had undergone renal transplantation 8 years previously after bilateral nephrectomy for renal AMLs and a 3-cm chromophobe renal cell carcinoma. Hepatocellular carcinoma was suspected during the initial cytologic and histologic examination based on the presence of numerous large polygonal cells with ample finely vacuolated or granular cytoplasm, low nucleocytoplasmic ratio, and mild nuclear pleomorphism in the smears, as well as a distinctive trabecular histologic pattern in the core biopsies. Immunoperoxidase stains showed that the neoplastic cells were negative for cytokeratins and positive for HMB45, Melan-A, and smooth muscle actin, establishing the diagnosis of epithelioid AML. To determine the distinguishing cytomorphologic features between epithelioid AML and HCC, we have compared the cytologic features of 15 cases of hepatic AML reported in the literature, including the present case, to the FNA cytologic findings of 38 consecutive cases of HCC diagnosed at out institution.

Topics: Adult; Angiomyolipoma; Biopsy, Fine-Needle; Carcinoma, Hepatocellular; Carcinoma, Renal Cell; Cell Nucleus; Cell Nucleus Shape; Cytoplasm; Diagnosis, Differential; Epithelioid Cells; Female; gp100 Melanoma Antigen; Humans; Kidney Transplantation; Liver; Liver Neoplasms; Magnetic Resonance Imaging; MART-1 Antigen; Melanoma-Specific Antigens; Nephrectomy

Renal angiomyolipoma (AML) may present as rare variants such as epithelioid and AML with epithelial cysts posing difficulties for the diagnosis to the surgical pathologist. We report a case of a 46-year-old male patient presenting a 5-cm solid tumor in the lower pole of the left kidney, with cystic changes at cut surface. The tumor exhibited 95% of epithelioid cells with atypical nuclei. A small focus of typical AML was observed. The immunoprofile of tumor cells was classical of AML including expression of melanocytic markers such as HMB45 and Melan A. We report the immunohistochemical study of the cystic component in an epithelioid AML. In contrast to the immunoreactivity reported in typical AML, the present case shows obvious expression of melanocytic markers in the cystic epithelial lining. This is strong evidence that these cysts are neoplastic and derived from AML, rather than entrapped native collecting duct epithelium.

Topics: Angiomyolipoma; Biomarkers, Tumor; Cysts; Epithelial Cells; Epithelioid Cells; gp100 Melanoma Antigen; Humans; Kidney Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Treatment Outcome

Angiomyolipoma (AML) is a rare mesenchymal neoplasm of the tumor, composed of a varying heterogeneous mixture of three tissue components: blood vessels, smooth muscle and adipose cells. Hepatic AML may demonstrate a marked histological diversity. We herein present one case of hepatic AML exhibiting prominent inflammatory cells in the background, which happened in a 61-year-old Chinese female patient, without signs of tuberous sclerosis. Histologically, the striking feature was the infiltration of numerous inflammatory cells in the background, including small lymphocytes, plasma cells, and eosnophils. The tumor cells were spindled and histiocytoid in shape, with slightly eosinophilic cytoplasm, and arranged along the vessels or scattered among the inflammatory background. Sinusoid structure was obviously seen in the tumor. Mature adipocytes and thick-walled blood vessels were focally observed at the boundaries between the tumor and surrounding liver tissues. The tumor cells were positive immunostaining for HMB-45, Melan-A, and smooth muscle actin. The inflammatory AML should be distinguished from other tumors with inflammatory background such as inflammatory myofibroblastic tumor and follicular dendritic cell tumor and deserves wider recognition for its occurrence as a primary hepatic tumor. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1828633072762370.

Topics: Actins; Angiomyolipoma; Biomarkers, Tumor; Diagnosis, Differential; Female; gp100 Melanoma Antigen; Hepatectomy; Humans; Immunohistochemistry; Inflammation; Liver Neoplasms; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Predictive Value of Tests; Treatment Outcome

Topics: Adult; Angiomyolipoma; Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Kidney Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Tumor Suppressor Protein p53

To study the pathologic features and immunophenotype of 3 cases of melanotic epithelioid clear cell tumor of kidney.. More than 2000 cases of renal tumors were retrospectively reviewed. Three cases of melanotic epithelioid clear cell tumor were identified. Immunohistochemical study was carried out using the paraffin-embedded tissue samples. Electron microscopy was also performed in 1 case.. Amongst the 3 cases studied, the male-to-female ratio is 1:2. Histologically, 2 cases showed a clear cell carcinoma-like pattern. Papillary structures covered by clear cells and eosinophilic cells were observed in 1 case. Immunohistochemical study showed that the tumor cells in all cases expressed HMB 45. Two of them were also positive for Melan A. The staining for epithelial markers and S-100 protein was negative. Melanosomes were not identified by ultrastructural examination.. Melanotic epithelioid clear cell tumor is a rarely seen neoplasm of kidney. There are some histologic overlaps with renal cell carcinoma, epithelioid angiomyolipoma and melanoma. Immunohistochemical study is useful in confirming the diagnosis. The tumor represents a morphologic variant of epithelioid angiomyolipoma.

Topics: Adolescent; Adult; Angiomyolipoma; Carcinoma, Renal Cell; Diagnosis, Differential; Epithelioid Cells; Female; Follow-Up Studies; Humans; Kidney Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Retrospective Studies

A unique case of a mixed epithelial stromal tumor (MEST) that was predominantly composed of adipose tissue is reported here. Radiographically and grossly, the lesion was thought to be an angiomyolipoma, based upon its fatty appearance. Microscopically, the lesion was predominantly composed of mature adipose tissue but also contained clusters of bland tubules surrounded by smooth muscle bundles and collagen. By immunohistochemistry, the stroma labeled diffusely for estrogen and progesterone receptors, while the muscle bundles labeled for desmin. Melanocytic markers HMB45 and Melan A, typically positive in angiomyolipoma, were nonreactive. This case expands the morphologic spectrum of MEST to include mimics of angiomyolipoma.

Topics: Adipose Tissue; Aged; Angiomyolipoma; Antigens, Neoplasm; Desmin; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Kidney Neoplasms; MART-1 Antigen; Melanoma-Specific Antigens; Neoplasm Proteins; Neoplasms, Complex and Mixed; Nephrectomy; Receptors, Estrogen; Receptors, Progesterone

Presented herein are two unusual epithelioid angiomyolipomas (AML) displaying prominent stromal sclerosis. Both patients were middle-aged women without a clinical history of tuberous sclerosis. One patient (case 1) had a 2 cm lesion arising in the renal cortex, and another (case 2) had a pararenal retroperitoneal tumor measuring 13 cm. Both tumors were composed of sheets or nests of polygonal epithelioid or short spindle cells having uniform round to oval nuclei and eosinophilic cytoplasm with cords of hyalinized sclerotic stroma between them. The tumor in case 2 had small areas of mature-looking fat cells. Immunohistochemically, epithelioid tumor cells were diffusely positive for actins and desmin in both cases, and melanoma antigen recognized by T cells (MART)-1 was positive in patient 2. Scattered HMB-45-immunoreactive cells were identified in the sclerotic cords of both tumors, but epithelioid tumor cells were essentially negative for HMB-45. The characteristic clinicopathological and immunohistochemical features of the present cases are analogous to a subset of epithelioid AML or sclerosing perivascular epithelioid cell tumors previously reported.

Topics: Angiomyolipoma; Antigens, Neoplasm; Biomarkers, Tumor; Epithelioid Cells; Female; Humans; Immunoenzyme Techniques; Kidney Neoplasms; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Retroperitoneal Neoplasms; Sclerosis

Renal angiomyolipoma is a tumor composed of varying amounts of fat, smooth muscle, and blood vessels. Characteristically, tumor cells express melanocytic markers such as HMB-45 and Melan-A. Recently, several other markers have been described as having excellent diagnostic sensitivity in cutaneous melanocytic lesions.. To compare the sensitivities of 5 melanocytic markers in renal angiomyolipoma and to study the expression patterns of these markers in the 3 different components of angiomyolipoma.. A tissue microarray of 20 renal angiomyolipomas was constructed. For each case, 3 cores containing fat, blood vessels, and smooth muscle were taken. The tissue microarray was then stained for HMB-45, Melan-A, tyrosinase, NK1-C3, and CD117.. HMB-45 was positive in 95%, Melan-A in 85%, NK1-C3 in 70%, tyrosinase in 50%, and CD117 in 40% of the cases. All (20/20) were positive for HMB-45 and Melan-A combined. These 5 markers had different sensitivities in the 3 components. HMB-45 was positive in 90%, 85%, and 80% of fat, smooth muscle, and blood vessel components, respectively; Melan-A in 70%, 60%, and 40%; NK1-C3 in 55%, 55%, and 45%; tyrosinase in 30%, 40%, and 10%; and CD117 in 20%, 40%, and 10%, respectively, of these 3 components.. HMB-45 and Melan-A combined were positive in 100% of the renal angiomyolipomas. We recommend the use of these 2 markers in the workup of this entity, including those with predominantly 1 component. Other melanocytic markers are of limited use. A tissue block comprising predominantly fat or smooth muscle components should be used when performing melanocytic marker immunostain.

Topics: Adipose Tissue; Adult; Aged; Angiomyolipoma; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Blood Vessels; Female; Gene Expression Regulation, Neoplastic; Humans; Kidney Neoplasms; Male; MART-1 Antigen; Melanocytes; Melanoma-Specific Antigens; Middle Aged; Monophenol Monooxygenase; Muscle, Smooth; Neoplasm Proteins; Proto-Oncogene Proteins c-kit; Sensitivity and Specificity

This report deals with 11 examples of renal angiomyolipomas (AML) which appear to include an epithelial element as a part of the neoplasm in the form of gross or microscopic cysts-usually both. There were seven females and four males between the ages of 20 and 70 years with mean age of 45 years. Three of these were known to be symptomatic: intermittent flank pain and gross hematuria for 2 months; recurrent hematuria both before and after flank trauma and a third patient with acute abdomen due to a ruptured tumor blood vessel. Cysts were described in three of the six cases where radiographic data were available. Seven tumors were in the right kidney and four in the left. In gross descriptions, cysts were mentioned in seven and they ranged from 6.0 to 2.0 cm with a median and mean maximal diameter of 5.0 and 4.0 cm, respectively. Microscopically, virtually all of the tumors included multiple smaller cysts and these were lined by flat, cuboidal or columnar epithelium and occasionally hobnail epithelium. There was usually a subepithelial collar of poorly differentiated cells, but the solid element of all tumors was myomatous angiomyolipoma; only one case had any adipose tissue. A dominant histological feature was the prominent lymphatic channels-identical to those of lymphangiomyomas and myomatous or triphasic AMLs. They are much more conspicuous in these cystic cases. Immunohistochemically, all tumors tested were reactive with actin, desmin and HMB-45, with the latter being more intensely positive in the subepithelial collars. Estrogen and progesterone receptors were usually positive, also. The behavior of these lesions appears to be no different from that of other AMLs.

Topics: Actins; Adult; Aged; Angiomyolipoma; Antigens, Neoplasm; Cysts; Desmin; Female; Humans; Immunohistochemistry; Kidney Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Muscle, Smooth; Neoplasm Proteins; Receptors, Estrogen; Receptors, Progesterone

The epithelioid variant of angiomyolipoma (EAML) is a rare tumor of unpredictable behavior that is composed of epithelioid, spindle, and giant cells and contains no or only a minimal amount of lipomatous tissue. The picture can lead to an erroneous diagnosis of renal cell carcinoma or sarcoma. We report on a case of EAML in the kidney of a 47-year-old female without any signs of tuberous sclerosis and review the literature. Grossly, a well-demarcated, spheroid, largely hemorrhagic tumor measuring 4.2 cm in diameter occupied the central third of the kidney. Histologically, it was solid, highly cellular, with occasional microcysts, composed of medium to large epithelioid cells with clear or oxyphilic cytoplasm, short spindle cells, and numerous giant multinucleated cells. After extensive sampling, adult-appearing fat tissue was found to present as rare foci of microscopic dimensions. Immunohistochemically, the tumor cells showed positive reactions with antibodies against HMB-45, melan A, CD-68, muscle-specific actin, and, rarely, smooth muscle actin. Cytokeratins and epithelial membrane antigen were negative. The EAML is a variant growing in a carcinoma-like pattern that can lead to an erroneous diagnosis of renal cell carcinoma. An extensive sampling and HMB-45 and CD-68 positivity combined with cytokeratin negativity are of paramount importance for the correct diagnosis. As a sporadic renal tumor it followed a benign course in most of the reported cases.

Topics: Actins; Angiomyolipoma; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Renal Cell; Diagnosis, Differential; Epithelioid Cells; Female; Giant Cells; Humans; Kidney Neoplasms; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Treatment Outcome

We report 3 recent cases of angiomyolipoma of the kidney. Although generally regarded as a benign neoplasm, angiomyolipoma rarely behaves in an aggressive manner, producing complicated clinical courses leading to metastasis and death. The presence of epithelioid elements within the tumor can result in difficulty differentiating benign from malignant angiomyolipoma and differentiating this tumor from renal adenocarcinoma. The presence of lymph node involvement can cause difficulty in differentiating multicentric disease in lymph nodes from metastasis to lymph nodes. The presence of cytologic abnormalities in the primary tumor can result in difficulty in differentiating atypia in benign angiomyolipoma from malignant sarcomatous transformation of a benign lesion. The 3 cases reported show many of these problems. Criteria for predicting malignancy in epithelioid tumors and sarcomatous transformation are not well recognized because of the rarity of this entity. The typical immunophenotype of all types of angiomyolipoma (cytokeratin-negative and melanomarkers-positive) is very useful in diagnosis but does not help in the differentiation from renal adenocarcinoma at frozen section. We report the empiric use of Ki67 and p53 in these cases as adjuncts to clinical and histologic assessment in predicting behavior. High Ki67 expression was a feature of malignant epithelioid angiomyolipoma. Low levels of p53 expression were seen in the angiomyolipoma with sarcomatous transformation. Benign angiomyolipomas were consistently negative for both Ki67 and p53.

Topics: Adult; Angiomyolipoma; Antigens, Neoplasm; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Kidney Neoplasms; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Tumor Suppressor Protein p53; Vimentin

Melanoma markers, especially the new microphthalmia transcription factor (mitf), have not been previously compared in hepatic and renal angiomyolipomas.. To evaluate expression of the novel melanocytic markers mitf and tyrosinase in angiomyolipomas, and to compare these markers with the established markers HMB-45 and melan-A in both hepatic and renal tumors.. Clinical, histopathologic, and immunohistochemical features of 15 hepatic angiomyolipomas were compared with those of 10 renal angiomyolipomas.. No significant differences between patients with hepatic angiomyolipomas and renal angiomyolipomas were found with respect to age, gender, race, and tumor size. Hepatic angiomyolipomas exhibited a predominance of the epithelioid smooth muscle cell component, in contrast to their renal counterparts, which were predominantly spindled. The smooth muscle cells expressed HMB-45 in 100% of cases in both groups, melan-A in 14 of 15 hepatic angiomyolipomas and 8 of 9 renal angiomyolipomas, mitf in 5 of 12 hepatic angiomyolipomas versus 6 of 10 renal angiomyolipomas, and tyrosinase in 3 of 12 and 2 of 10 hepatic angiomyolipomas and renal angiomyolipomas, respectively. The extent and intensity of immunostaining with HMB-45 and melan-A were dependent on whether spindled or epithelioid cells predominated; the epithelioid cells showed stronger and more widespread reactivity than the spindled cells.. We believe that the best immunohistochemical marker for confirming the diagnosis of angiomyolipoma is HMB-45, followed by melan-A. Routine use of mitf and/or tyrosinase is not indicated.

Topics: Adult; Aged; Angiomyolipoma; Antigens, Neoplasm; Biomarkers, Tumor; DNA-Binding Proteins; Female; Humans; Immunohistochemistry; Kidney Neoplasms; Liver Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Microphthalmia-Associated Transcription Factor; Middle Aged; Monophenol Monooxygenase; Neoplasm Proteins; Transcription Factors

The diagnosis of metastatic malignant melanoma (MMM) may be difficult in surgical pathology, often complicated by the unpredictable spread of this tumor and its great variability on histologic evaluation. Traditionally used immunohistochemical markers on melanomas are insufficient because of either a relative lack of specificity (S100 protein) or variably reported sensitivity (HMB45). Information about some newer markers, such as tyrosinase (TYR) and Melan A, is more limited. Recently, based on the study of a small number of tumors, it was suggested that microphthalmia transcription factor (MITF) is 100% sensitive in the identification of metastatic melanoma. In the current study, we compared the diagnostic usefulness of MITF with that of four other markers in 266 cases of conventional metastatic melanomas from different sites, 33 cases of desmoplastic melanomas, and 1 case of melanoma with rhabdoid features. The specificity of MITF was evaluated by using a representative sample of control tumors. Microphthalmia transcription factor with nuclear positivity was seen in 235 of 266 cases of conventional MMM (88%), usually in more than 30% of tumor cells. However, some melanomas had only foci of MITF- and TYR-positive cells, whereas the majority of cells were generally S100 protein-positive. Only 1 of 30 desmoplastic melanomas (3%) had MITF-positive cells, representing epithelioid foci resembling conventional melanoma. Two cases had TYR in a similar pattern; all were HMB45-negative. One metastatic melanoma with rhabdoid features was negative for MITF and other markers except the S100 protein. Half of the S100 protein negative conventional melanomas (6 of 12) were MITF-positive, whereas 4 of 20 (20%) TYR-negative tumors had reactivity for MITF. The percentages of positive cases of MMM (10% or more tumor cells positive) diagnosed with the four other markers in descending order were 90% (S100 protein and TYR), 78% (melan-A), and 66% (HMB45). Microphthalmia transcription factor appeared to be specific, because significant reactivity was not found in 112 carcinomas, 20 lymphomas, 20 angiosarcomas, 20 fibrous histiocytomas, and 20 malignant peripheral nerve sheath tumors. However, positive nuclei were found focally among reactive histiocytes, especially in osteoclasts, epithelioid histiocytes, and sporadic other histiocytes. Microphthalmia transcription factor may be a valuable addition to the marker panel used in diagnosing melanoma, in combination with S100, TYR,

Topics: Angiomyolipoma; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; DNA-Binding Proteins; Fluorescent Antibody Technique, Indirect; Histiocytes; Humans; Lymphangiomyoma; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Microphthalmia-Associated Transcription Factor; Monophenol Monooxygenase; Neoplasm Proteins; S100 Proteins; Sensitivity and Specificity; Skin Neoplasms; Transcription Factors

To study the clinicopathologic features of hepatic angiomyolipoma (AML) and to investigate the feasibility of a new antibody-A103 as a diagnostic aid for AML.. Ten cases of AML were retrieved from hospital records and analyzed morphologically. Immunohistochemistry was performed on paraffin-embedded tissues with a panel of antibodies, including antibody-A103.. There were eight women and two men, with ages ranging from 38-58 years (median 45.7). Clinically, nine cases were asymptomatic and found by imaging techniques. None of the patients had associated tuberous sclerosis. All tumors were sharply demarcated from the surrounding liver parenchyma. Histologically they were composed of a heterogeneous mixture of three components: thick-walled blood vessels, spindle or epithelioid smooth muscle cells and adipose tissue. All tumors showed a strong immunoreactivity to A103, HMB-45 and smooth muscle actins. Follow-up information on all 10 cases showed a benign course with no signs of recurrence.. Hepatic AML is a rare mesenchymal tumor of the liver. A103 is a promising marker for a pathologic diagnosis of hepatic AML.

Topics: Actins; Adult; Angiomyolipoma; Antigens, Neoplasm; Desmin; Female; Humans; Immunohistochemistry; Liver Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Muscle, Smooth; Neoplasm Proteins; Platelet Endothelial Cell Adhesion Molecule-1; S100 Proteins; Vimentin

Angiomyolipomas are tumours of uncertain histogenesis, most often occurring in association with the kidney. A characteristic finding is their reactivity with HMB-45, a monoclonal antibody to the melanocyte-associated antigen gp-100. We tested 18 angiomyolipomas for their reactivity with A103, a monoclonal antibody to Melan-A (MART-1), another melanocyte-associated marker, and compared it with HMB-45. All cases were positive with both antibodies, yet most cases showed a more homogeneous staining pattern with A103. Normal kidney was immunohistochemically negative for both antibodies. We also performed RT-PCR assays for gp-100 and Melan-A in 4 of the 18 angiomyolipoma samples and in three normal kidney samples. All 4 angiomyolipoma specimens revealed mRNA for both melanocyte differentiation markers. gp-100 mRNA was found in the samples of normal kidney, but Melan-A mRNA was not. Our study shows that angiomyolipomas express the melanocyte-associated antigens Melan-A and gp-100 at the protein and at the mRNA level, suggesting a true expression of these antigens rather than cross-reacting epitopes. Based on the mRNA expression pattern, immunohistochemical analysis is the preferred method for the detection of gp-100, while Melan-A can be used at the protein and mRNA levels. Our study demonstrates that A103 is a useful marker for the diagnosis of angiomyolipomas.

Topics: Angiomyolipoma; Antigens, Neoplasm; Biomarkers, Tumor; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Kidney Neoplasms; Liver Neoplasms; MART-1 Antigen; Melanocytes; Membrane Glycoproteins; Neoplasm Proteins; Reverse Transcriptase Polymerase Chain Reaction; Staining and Labeling

Melan-A is a previously defined, melanocyte differentiation antigen, and an anti-Melan-A murine monoclonal antibody, A103, was recently developed by our group. In this study, we evaluated A103 immunoreactivity on formalin-fixed, paraffin-embedded tissues, exploring the potential of A103 in the diagnosis of metastatic melanoma. Seventy-five metastatic melanomas, 10 primary melanomas, and 10 benign melanocytic nevi were tested. The reactivity of A103 was compared with HMB-4, an anti-gp100 antibody. Results showed that all nevi were A103 positive, and most primary melanomas were A103 and HMB45 positive. Of 75 metastatic melanomas, 61 (81%) were A103 positive, and 56 (75%) were HMB45 positive. Of 19 HMB45-negative lesions, 8 were A103 positive; of 14 A103-negative lesions, 3 were HMB45 positive. Eleven metastatic lesions, as well as 2 of 10 primary melanomas, were dual negative. These negative cases consisted mainly of the spindle cell and desmoplastic variants. Of the positive cases, A103 showed homogeneous staining in a significantly higher proportion of cases than HMB45 (72% versus 52%). In addition, focal staining with less than 5% reactive tumor cells was seen more frequently in HMB45 (12 of 56) than in A103 (5 of 61). These results indicated that A103 can be used as a first-line antibody in the diagnosis of metastatic melanoma. Our results also showed that A103 reacted with angiomyolipoma, which is known to be HMB45 positive. Of normal tissues, unexpected A103 reactivity was observed in the adrenal cortex, granulosa and theca cells of the ovary, and Leydig cells of the testis. This A103 immunoreactivity in benign and neoplastic tissues of nonmelanocytic origin, the basis of which is unclear, could also be of potential diagnostic value.

Topics: Angiomyolipoma; Antibodies, Monoclonal; Antigens, Neoplasm; Female; Humans; Immunohistochemistry; Male; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Neoplasm Proteins; Nevus; Paraffin Embedding; Skin Neoplasms; Tissue Distribution

The antibody to the melanoma antigen recognized by T cells (anti-MART-1, clone M2-7C10) is a newly described antibody to a transmembrane protein previously detected only in normal skin melanocytes, retinal tissue, and malignant melanoma (MM). This antibody is the basis for ongoing immunotherapy protocols at the National Institutes of Health/National Cancer Institute. HMB-45, an antibody directed against a premelanosome glycoprotein, although used predominantly for the diagnosis of MM, has shown consistent staining in angiomyolipoma (AML), lymphangiomyoma/lymphangiomyomatosis (LAM), and clear cell sugar tumor (CCST), a group of tumors proposed to be related on the basis of their common perivascular epithelioid cells, which exhibit various degrees of smooth muscle differentiation, melanogenesis, and intracytoplasmic membrane bound granules. To compare the immunoreactive patterns of anti-MART-1 with those of HMB-45, we performed avidin-biotin immunoperoxidase testing on nonmelanocytic neoplasms (AMLs, LAMs, CCSTs) known to express HMB-45. Microwave pretreatment was necessary for anti-MART-1 staining on paraffin-embedded material. Our results showed that all of the 10 cases of AML were immunoreactive for both anti-MART-1 and HMB-45; that all of the 4 cases of LAM were positive for HMB-45, with 1 of the 4 reacting with anti-MART-1; and that 3 of the 4 cases of CCST expressed HMB-45, whereas 1 of the 4 was positive for anti-MART-1. Our findings lent additional support to previous studies that proposed a relationship between AML, LAM, and CCST. Anti-MART-1 and HMB-45 share similar specificities for these nonmelanocytic tumors, but the former seems to be a less sensitive marker for these lesions. In similar circumstances, anti-MART-1 and HMB-45 are potentially useful clinical markers.

Topics: Adenocarcinoma, Clear Cell; Angiomyolipoma; Antigens, Neoplasm; Humans; Immunoenzyme Techniques; Lymphangioleiomyomatosis; MART-1 Antigen; Melanoma-Specific Antigens; Neoplasm Proteins; T-Lymphocytes; Tumor Cells, Cultured