Perivascular epithelioid cell tumor of the uterus: immunohistochemical, ultrastructural and molecular study

A case of perivascular epithelioid cell tumor of the uterus is reported, occurring in a 32-year-old woman. The tumor (8.0 cm in dimension) showed exophytic growth from the outer half of the myometrium. Histopathologically, the tumor was composed of thick blood vessels and perivascular epithelioid cells. The neoplastic cells were strongly immunoreactive for HMB45 antigen, CD117 (c-kit), vimentin and the progesterone receptor, but completely negative for S-100 protein, smooth muscle actin, desmin, CD34, the estrogen receptor and p16. The Ki-67 labeling index was low (1.25%). Ultrastructurally, the neoplastic cells had numerous premelanosomes with some glycogen deposits. Single-stranded DNA conformational polymorphism of p53 and methylation-specific polymerase chain reaction of p16 revealed negative results. Definite melanosomes on electron microscopic analysis and coexpression of HMB45 antigen and stem cell factor receptor (CD117) may provide the clue to understanding perivascular epithelioid cell tumor because angiomyolipoma also coexpresses HMB45 antigen and CD117.     

A uterine leiomyosarcoma that became positive for HMB45 in the metastasis

Uterine smooth muscle tumors are usually spindle cell lesions, but a minority is composed of epithelioid cells. Foci of clear cells can be found in these latter tumors. Recently, it has been shown that some of these tumors can be positive for HMB45, and some authors have advocated calling these lesions perivascular epithelioid cell (PEC) tumors or PEComas. The case we describe here clearly shows that the so called PEC is just a smooth muscle cell capable of changing its immunophenotype. The patient involved is a 29-year-old black woman who was found to have an epithelioid leiomyosarcoma of the uterus in November 1995. She was treated with a simple hysterectomy and bilateral salpingo-oophorectomy. A metastatic lesion was found in her liver. She, therefore, also received chemotherapy and was free of disease until October 2002, when a recurrent tumor was detected in her spine. After undergoing resection of the lesion at 2 different times, in 2002 and 2003, the patient was treated with radiotherapy and is currently receiving chemotherapy. On microscopic examination, the tumor in the uterus and liver both proved to be an epithelioid leiomyosarcomas that was diffusely positive for smooth muscle actin. Approximately 15% of the cells had clear cytoplasm, but sections from 2 different blocks were completely negative for HMB45. However, although the tumors resected from the spine in 2002 and 2003 showed features similar to those of the uterine neoplasm, but with a lower percentage of cells positive for smooth muscle actin and more clear cells, several of the clear cells were positive for HMB45. To the best of our knowledge, this is the first case of a uterine smooth muscle cell tumor that became positive for HMB45 when it metastasized.     

Uterine tumour resembling ovarian sex cord tumour is an immunohistochemically polyphenotypic neoplasm which exhibits coexpression of epithelial, myoid and sex cord markers

AIMS: To describe the clinicopathological and immunohistochemical findings in four cases of uterine tumour resembling ovarian sex cord tumour (UTROSCT). METHODS: Four UTROSCTs were stained with a wide range of antibodies, including epithelial (AE1/3, epithelial membrane antigen), myoid (desmin, alpha smooth muscle actin, h-caldesmon), sex cord (alpha inhibin, calretinin, melan A, CD99) and neuroendocrine (chromogranin, CD56) markers as well as hormone receptors (oestrogen receptor, progesterone receptor, androgen receptor), vimentin, CD10, WT1 and HMB45. RESULTS: The tumours ranged from 0.8 to 19.5 cm. Three were relatively well circumscribed intramural myometrial lesions; the other was a pedunculated mass attached to the uterine serosa. The tumours were variably composed of solid, corded, trabecular, nested, glandular and retiform arrangements of tumour cells. In three cases, cells with eccentric nuclei and abundant eosinophilic cytoplasm, resulting in a rhabdoid appearance, were a prominent feature. Three cases were diffusely positive with AE1/3 and all with epithelial membrane antigen. Positivity with myoid markers was common with 3, 4 and 1 case respectively staining with desmin, alpha smooth muscle actin and h-caldesmon; 2, 4, 1 and 2 cases respectively were positive with alpha inhibin, calretinin, melan A and CD99. All were chromogranin negative and exhibited diffuse strong staining with CD56. All were diffusely positive with oestrogen receptor, progesterone receptor, vimentin and WT1. Three cases were androgen receptor positive and all were CD10 and HMB45 negative. CONCLUSIONS: UTROSCT exhibits a polyphenotypic immunophenotype with coexpression of markers of epithelial, myoid and sex cord lineage as well as hormone receptors.     

Hepatic angiomyolipoma resembling an inflammatory pseudotumor of the liver. A case report

Hepatic angiomyolipoma (AML) may demonstrate a marked histologic diversity and is frequently misdiagnosed. HMB45 is a promising marker for this tumor and is expected to facilitate the recognition of some AMLs with unusual morphology. We report on a case of hepatic AML exhibiting histologic features that were similar to inflammatory pseudotumor (IPT) or to IPT-like follicular dendritic cell (FDC) tumor of the liver. The patient was a 21-year-old Japanese woman with a mass in the left lobe of the liver (70 x 73 mm). There were no clinical features of tuberous sclerosis. Histologically, numerous inflammatory cells, including small lymphocytes, plasma cells, and histiocytes, showed diffuse infiltration throughout the lesion. However, the present case also shared some of the morphologic findings of hepatic AML, including clusters of smooth muscle cells with clear cytoplasm, a few scattered adipose cells, and thick-walled blood vessels. Moreover, the smooth muscle cells consisted of spindle-shaped cells or larger, more rounded cells with either clear cytoplasm or eosinophilic epithelioid cell features positive for vimentin, muscle-specific actin, and smooth muscle actin. HMB45 immunostaining confirmed the diagnosis of AML. The present case indicates that IPT or IPT-like FDC tumor should be added to the list of differential diagnoses for AML of the liver.     

Large lipoleiomyoma of the uterine body

Large or giant lipoleiomyoma of the uterine corpus is a rare condition. A 70-year-old Japanese woman consulted our hospital because of a pelvic mass and abnormal uterine bleeding. Physical examination showed a mass in the pelvis. Blood laboratory test showed anemia and leukocytosis. Cholesterol, triglyceride, glucose, and hemoglobin A1c were normal. Tumor markers (CEA, CA19-9, CA125, SCC, and CA72-4) were normal. Imaging modalities including ultrasound and computed tomography revealed a characteristic large (8 × 8 × 9 cm) tumor in the posterior aspect of the uterine body. The tumor was characteristic, and the opacity was heterogenous. Radiologists' diagnosis was angiomyolipoma. Simple hysterectomy and bilateral salpingo-oophorectomy were performed. During the operation, it was found that the mass originated from the posterior aspect of the uterine body. Grossly, the resected mass was heterogenous and whitish yellow. It measured 10 × 9 × 9 cm. The tumor originated from the myometrium and assumed features of subserosal leiomyoma. Histologically, the tumor was composed of adipose tissue and smooth muscle cells. The adipose tissue was mature, and there were no atypical cells or lipoblasts. The smooth muscle areas were composed of red spindle smooth muscle cells. No atypia was seen in the smooth muscles. Mitotic figures were not recognized. Vascular proliferation was not seen. The adipose tissue element accounted for 20% in area; and the smooth muscle element, 80%. Immunohistochemically, the adipose tissue element was positive for vimentin and S100 protein, and negative for pancytokeratins (AE1/3, CAM5.2), α-smooth muscle actin, desmin, CD34, HMB45, p53, MDM2, CDK4, and KIT. The smooth muscle element was positive for vimentin, desmin, and α-smooth muscle actin, but negative for pancytokeratins (AE1/3, CAM5.2), S100 protein, CD34, HMB45, p53, MDM2, CDK4, and KIT. The Ki-67 labeling was approximately 0.3% in the smooth muscle element and approximately 0.2% in the adipose tissue element. The pathological diagnosis was large lipoleiomyoma of the uterine body. The patient is now free of the tumor 2 years after the operation.     

Uterine lipoleiomyoma: a histopathological review of 17 cases

Lipoleiomyoma is a rare uterine tumor. The exact frequency and proliferation activity are not yet known. This study aims to know the frequency and evaluate the relation with renal angiomyolipoma. Lipoleiomyoma cases were immunohistochemically stained by antibodies for Ki-67, melanoma specific antigen HMB45, S-100 protein, and alpha smooth muscle actin (alpha-SMA). Frequency of uterine lipoleiomyoma among uterine myomatous tumor was 17/4904 (0.35%) in the Department of Human Pathology, Field of Oncology, Kagoshima University Graduate School database (1983-2003). Patients ranged from 45 to 74 years of age, and 10 cases were associated with leiomyoma. Six of 17 (35%) cases showed areas with renal angiomyolipoma-like vessels and atypical cellular features. Immunostaining was available in 12 cases. By Ki-67 labeling index, both muscle (average 1.38%) and fat (average 1.17%) portions of the tumor had greater proliferation than normal myometrium (average 0.76%), which suggests that fat portions of the tumor are proliferating adipose tissue rather than fatty degeneration of muscular counterpart. HMB45 antigen, which is positive in renal angiomyolipoma, was negative in three uterine cases having angiomyolipoma-like vessels (3/12). However, HMB45 antigen was positive in spindle-shaped tumor cells of three cases (3/12) which lacked angiomyolipoma-like vessels. Presence of angiomyolipoma-like blood vessels in these tumors is not an uncommon feature. However, the diagnosis of uterine angiomyolipoma should not be based on the result of HMB45 antigen immunoreactivity alone.     

子宫血管周上皮样细胞肿瘤临床病理观察

目的研究子宫血管周上皮样细胞肿瘤的病理学特征、诊断、鉴别诊断和生物学行为。方法对5例子宫血管周上皮样细胞肿瘤进行常规组织学和免疫组织化学（SP法）染色和观察,对患者进行随访,并复习相关文献。结果光镜下5例肿瘤均由透明或嗜酸细胞巢或宽窄不等的细胞索组成,间质有丰富的小血管和程度不等的透明变。免疫组织化学染色示5例瘤细胞均黑色素细胞标记阳性和程度不等的结蛋白和平滑肌肌动蛋白（SMA）阳性,CK和CD10阴性。5例患者现均存活。结论子宫血管周上皮样细胞肿瘤具有较特征性的组织病理及免疫组织化学特点,HMB45阳性对诊断有重要作用。该肿瘤分良性、恶性潜能不能确定和恶性三类,应与透明细胞癌和上皮样平滑肌肿瘤区别。     

Characterization of smooth muscle components in renal angiomyolipomas: Histological and immunohistochemical comparison with renal capsular leiomyomas

The smooth muscle components of angiomyolipoma (AML) of the kidney have a wide histological and immunohistochemical spectrum. In the present study, 50 cases of AML and seven cases of renal capsular leiomyoma (RCL) were reviewed histologically and immunohistochemically, and the results compared with those of leiomyomas of soft parts. The AML cases were subclassified into 34 cases of common, 12 of leiomyomatous and four of lipomatous type. Even the common-type AML tissues showed a variety of histologic features, including lymphangiomyoma. The cytoplasm of leiomyomatous cells in AML was usually plump and eosinophilic, but sometimes clear with abundant glycogen, and an ovoid or irregular cleaved nucleus. AML cells, irrespective of whether they were epithelioid or leiomyomatous, stained positively for HMB45, S100 protein, and α-smooth muscle actin. RCL cells had histologic features identical to those of the leiomyomatous cells in AML. Moreover, the immunohistochemical profiles of the RCL cells were also identical to those of AML. These morphologic and immunohistochemical findings are different from those of smooth muscle tumors in soft parts and confirm that AML and RCL are closely related proliferative entities.     

Perivascular epithelioid cell (PEC) tumors of the uterus: a clinicopathologic study of two cases with aggressive features.

We report the clinicopathologic, immunohistochemical and ultrastructural features of two unusual tumors of the uterus composed of spindle and epithelioid cells strongly positive for HMB45. The two patients of 56 and 48 years of age had, respectively, hemoperitoneum and abnormal uterine bleeding. Morphologically, both tumors showed atypia and extensive necrosis. The neoplastic cells express immunohistochemically both melanogenesis (HMB45) and smooth muscle markers (actin). Ultrastructural analysis showed the presence of intracytoplasmic membrane-bound granules. We viewed these neoplasms as perivascular epithelioid cell (PEC) tumors with aggressive features. Follow-up has shown the death of one patient whereas the other is alive without disease 36 months after the surgery. The two patients were evaluated for signs of tuberous sclerosis complex, and findings were negative.     

Hepatic epithelioid angiomyolipoma with trabecular growth pattern: a mimic of hepatocellular carcinoma on fine needle aspiration cytology

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.     

Angiomyolipoma with epithelial cysts of the kidney in a man

Angiomyolipoma (AML) is a well-characterized tumor composed of vascular, smooth muscle and adipose elements. Recently, AML with epithelial cysts (AMLEC) has been described as a cystic variant of AML. Herein is reported an AMLEC in a 55-year-old man, and to the authors' knowledge this is the first case report of AMLEC in Japan. He was referred to hospital because of microhematuria. A left renal tumor was noted and partial nephrectomy was performed. Histology indicated that the tumor was composed of epithelial cysts, compact subepithelial stroma and muscle-predominant AML. Immunohistochemically, the subepithelial compact stroma and muscle-predominant AML were positive for HMB-45, estrogen receptor (ER), progesterone receptor (PR), CD10, smooth-muscle actin and desmin. Epithelial cysts were positive for pancytokeratin but negative for HMB-45, ER and PR. This tumor was diagnosed as AMLEC, mainly based on the immunohistochemical result that subepithelial compact stroma and muscle-predominant AML were positive for HMB-45. The patient was alive with no evidence of recurrence at 2 years postoperatively. This case was very interesting because it suggests that AMLEC should enter into the differential diagnosis of adult renal neoplasms.     

肾混合性上皮间质肿瘤和成人囊性肾瘤的临床病理学观察

目的 探讨肾混合性上皮间质肿瘤(MEST)和成人囊性肾瘤的临床病理学特点、免疫表型和鉴别诊断.方法 通过HE和免疫组织化学染色(EnVision法)分析5例MEST和4例囊性肾瘤,并复习有关文献.结果 5例MEST均为女性,中位年龄45岁;囊性肾瘤中男性3例,女性1例,中位年龄41岁;临床表现为腰痛或血尿.大体观察:MEST界清无包膜,切面未见明显出血坏死,其中3例旱实性,1例呈囊实性,另1例呈多囊性其间为厚的纤维分隔;囊性肾瘤有包膜,切面呈多囊性,囊壁薄,无实区和坏死厌.镜下观察:MEST由不等量增生、囊性扩张的腺上皮与不同排列方式的梭形间质细胞混合组成,两种细胞成分无明显异形,2例局部衬覆子宫内膜样或输卵管样上皮;囊性肾瘤为多房囊腔组织,囊壁薄,内衬单层上皮.免疫表型:9例上皮细胞CKpan、上皮细胞膜抗原(EMA)均呈阳性表达;MEST间质梭形细胞波形蛋白(5/5)、平滑肌肌动蛋白(SMA,3/5)、结蛋白(4/5)、CD10(5/5)、ER(4/5)和PR(4/5)呈阳性表达,HMB45、CD34、CD117和S-100蛋白呈阴性;囊性肾瘤间质成分波形蛋白(4/4)、SMA(4/4)、结蛋白(1/4)阳性,ER(3/4)和PR(1/4)少量细胞阳性,CDIO、HMB45、CD34、CDll7和S-100蛋白呈阴性.结论 (1)MEST和囊性肾瘤均是少见的肾脏肿瘤,大多为良性.(2)MEST间叶细胞呈不同程度的平滑肌或肌纤维母细胞分化;2例有MaUerian管上皮分化特征.(3)MEST和成人囊性肾瘤在形态学和免疫表型上有很多相似性,可能为位于同一肿瘤谱系两端的肿瘤.     

Leiomyomatosis-like lymphangioleiomyomatosis of the colon in a female with tuberous sclerosis.

Smooth muscle lesions of the large bowel, excluding the rectum, are generally rare, and diffuse smooth muscle lesions, termed leiomyomatosis, are even rarer. In this report, we document, for the first time, leiomyomatosis-like lymphangioleiomyomatosis (LAM) of the ascending, transverse, and descending colon in association with bilateral renal angiomyolipoma (AML) in a 30-year-old Chinese female with tuberous sclerosis complex (TSC). She presented with protracted constipation for which a colectomy was performed. Histology disclosed multiple confluent nodular CD34 and CD117 negative smooth muscle proliferation within the large bowel wall, whereas the renal biopsy revealed typical features of AML. Interestingly, the epithelioid smooth muscle cells of both the colonic and renal lesions were HMB45 positive, suggesting that leiomyomatosis-like LAM of the colon, pulmonary LAM and AML are closely related entities. The patient remained free of complications for the last five years after surgery. Leiomyomatosis-like LAM of the large bowel probably represents another manifestation of the tendency of TSC to be associated with proliferative lesions.     

Mucocutaneous angiomyolipoma. A report of 2 cases arising in the nasal cavity.

OBJECTIVE: Angiomyolipoma (AML) is a distinctive tumor that usually occurs in the kidney and rarely in the liver. Angiomyolipoma of other sites is extremely rare, and, to our knowledge, only 2 cases have been described in the nasal cavity. We present 2 additional cases of AML of the nasal cavity and discuss the difference between them and renal AML. CASE REPORTS AND PATHOLOGIC FINDINGS: Two tumors in a 66-year-old man and an 88-year-old woman without tuberous sclerosis are described. They showed 20-mm, well-circumscribed, polypoid shapes. Histologically, they were composed of mature smooth muscle cells, fat cells, and various-sized blood vessels. In addition, aggregated small lymphocytes were noted. Neither epithelioid smooth muscle cells nor HMB45 immunoreactivity was seen in either case. CONCLUSIONS: The clinicopathologic features of AML of the nasal cavity are distinct from renal and hepatic AML and are common to those of AML arising in the skin and oral and pharyngeal mucosa. The term mucocutaneous angiomyolipoma is thought to be appropriate to express these characteristic tumors.     

Monotypic epithelioid angiomyolipoma of the adrenal gland: an unusual site for a rare extrarenal tumor

Epithelioid angiomyolipoma (AML) is an uncommon renal mesenchymal tumor with malignant potential and is frequently associated with tuberous sclerosis. Extrarenal AMLs are rare, and to the best of our knowledge, this is the first reported case of a primary monotypic epithelioid AML of adrenal gland in a patient without evidence of tuberous sclerosis. The patient is a 42-year old man who presented with retroperitoneal hemorrhage resulting from spontaneous rupture of adrenal mass. Histologically, the tumor showed a prominent component of epithelioid smooth muscle cells with slightly pleomorphic nuclei, sometimes with prominent nucleoli and eosinophilic cytoplasm resembling oncocytic tumors. Epithelioid cells were positive for melanoma (HMB45 and positive MelanA) and smooth muscle markers (α-smooth muscle–specific actin), but not for epithelial markers (cytokeratin, EMA). Differential diagnosis from renal cell carcinoma, adrenal gland carcinoma, and metastatic carcinoma is often challenging because of its epithelioid morphology. Because primary and secondary malignant tumors are much more common and aggressive neoplasms, establishing the correct diagnosis has important therapeutic and prognostic implications.     

Myxoid mixed low-grade endometrial stromal sarcoma and smooth muscle tumor of the uterus. Case report

We report the case of a 73-year-old female with myxoid mixed low-grade endometrial stromal sarcoma and smooth muscle tumor of the uterus. Grossly, the tumor sized 130 x 130 x 100 mm involved the uterine corpus almost in its entirety. Histologically, the tumor consisted of two cell types. In some areas, the tumor cells showed typical features of endometrial stromal tumors and resembled stromal cells of proliferative endometrium. In other areas, however, the tumor showed smooth muscle features and consisted of larger mostly epitheloid cells with a moderate amount of cytoplasm. In all areas, myxoid changes and multiple hyalinizing giant rosettes were present. The tumor infiltrated the myometrium in a pattern typical of low-grade endometrial stromal sarcoma. Immunohistochemically, the tumor cells showed expression of vimentin, estrogen and progesterone receptors and variable expression of CD10, α-smooth muscle actin, desmin, h-caldesmon, and cytokeratin AE1/AE3. Other markers examined including CD99, α-inhibin, cytokeratin CAM5.2, S-100 protein, and HMB45 were negative. To the best of our knowledge, mixed low-grade endometrial stromal and smooth muscle tumor with myxoid changes has not been described to date.     

Malignant angiomyolipoma of the liver: a hitherto unreported variant

AIMS: After their original recognition in the kidney, angiomyolipomas (AMLs) have been reported in the liver for more than 20 years. In the kidney, five cases of malignant AML have been reported. We report the first case of malignant hepatic AML. METHODS AND RESULTS: A 70-year-old female patient presented with abdominal discomfort. Clinical examination revealed a palpable liver. CT scan showed a polymorphous hypervascular lesion in the right liver lobe. A biopsy was taken and resulted initially in a differential diagnosis between a hepatocellular carcinoma, a metastatic tumour (possibly of renal origin) and angiomyolipoma (AML). After immunohistochemistry, a hepatic AML was suggested, given the immunoreactivity for HMB45/NKIC-3. The mass was resected 5 years later because of relapsing abscess formation. Gross examination of the resection specimen showed a focally encapsulated brown mass with focal necrosis. Microscopic examination showed a tumour growing in sheets, separated by sinusoidal-like vessels. Most of the tumour cells had a large, polygonal, clear cytoplasm, often with eosinophilic condensation around the nucleus. There was prominent vascular invasion. Immunohistochemistry (reactivity for HMB-45, NKIC-3, S100 and alpha smooth muscle actin, negativity for cytokeratin and vimentin) and electron microscopy confirmed the diagnosis of monomorphic epithelioid AML with prominent vascular invasion. Seven months after tumour resection, the patient died of recurrent disease. CONCLUSIONS: This case highlights the importance of immunohistochemistry and electron microscopy in diagnosing this type of tumour. Possibly, in the past, malignant AML of the liver has been misdiagnosed as HCC.     

Monotypic epithelioid angiomyolipoma of the liver

AIMS: Monotypic epithelioid angiomyolipoma is a recently recognized renal tumour, which is composed purely of epithelioid cells coexpressing markers of both smooth muscle differentiation and melanogenesis (HMB45). We report here the first case of monotypic epithelioid angiomyolipoma arising in the liver. CASE DETAILS: A 30-year-old woman without tuberous sclerosis complex (TSC) was incidentally found to have a hepatic mass by ultrasonography. Grossly, the resected tumour showed a nodule-in-nodule appearance, with large areas of haemorrhagic necrosis. Microscopically, the tumour was composed of pleomorphic epithelioid cells with clear, eosinophilic cytoplasm. Neither adipocytes nor abnormal vessels were recognized in the tumour. Immunohistochemically, the tumour cells were strongly positive for HMB45 and S100 protein, focally positive for desmin, vimentin and smooth muscle actin, and negative for epithelial markers (cytokeratins, EMA). Ultrastructural analysis showed numerous dense granules with some striated ones resembling melanosomes, myofilaments and pinocytic vesicles in the cytoplasm. Molecular analysis showed no allelic loss of the TSC2 region or 12 other chromosomal regions. The patient is free of disease over 1 year after the operation. CONCLUSION: We consider that this hepatic tumour is closely related to angiomyolipoma, and a counterpart of renal monotypic epithelioid angiomyolipoma.