Utility of glypican‐3 and survivin in differentiating hepatocellular carcinoma from benign and preneoplastic hepatic lesions and metastatic carcinomas in liver fine‐needle aspiration biopsies

Glypican‐3 (GPC‐3), a membrane‐anchored heparin sulfate proteoglycan, has been shown to be expressed in ～80% of hepatocellular carcinoma (HCC) but not in benign hepatic lesions. Survivin, a novel inhibitor of apoptosis, and a prognostic marker, has also been expressed in HCC. We evaluated these two immunomarkers (GPC‐3 and survivin) in differentiating HCC from benign and preneoplastic hepatic lesions and metastatic carcinomas, comparing them to HepPar‐1 (hepatocyte paraffin‐1) in liver fine‐needle aspiration biopsies (FNAB). Immunohistochemistry for GPC‐3, survivin and HepPar‐1 was performed on 92 FNAB including HCC, hepatic cirrhosis, focal nodular hyperplasia (FNH), hepatic adenoma, dysplastic hepatic nodules and metastatic carcinomas. Immunostaining was scored as positive, if ≥10% of tumor cells stained. GPC‐3 is immunoexpressed in 56.8% of HCC, but not in benign and preneoplastic hepatic lesions, or metastatic carcinomas; whereas survivin is expressed in HCC (86.4%), benign hepatic lesions (85.7%), dysplastic hepatic nodules (100%) and metastatic carcinomas (94.3%). HepPar‐1 is immunoexpressed in HCC (72.7%), benign hepatic lesions (100%), dysplastic nodules (100%) and metastatic carcinomas (2.9%). The sensitivity and specificity of GPC‐3, survivin and HepPar‐1 for detection of HCC are 56.8 and 100%, 86.4 and 6.3%, 72.7 and 70.8%, respectively. GPC‐3 is a reliable and more specific immunohistochemical marker than survivin for the diagnosis of HCC in FNAB. HepPar‐1, although a more sensitive marker than GPC‐3, has a lower specificity for detection of HCC. Our data supports the potentially significant diagnostic utility of GPC‐3 in FNABs in differentiating primary malignant from benign and preneoplastic liver lesions, and metastatic carcinomas. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Malignant angiomyolipoma in the liver: a case report with pathological and molecular analysis

Malignant angiomyolipoma (AML) of the liver is rare. We report a case of AML with malignant transformation and metastases. A 30-year-old man had developed giant hepatic masses. Microscopically, the periphery of the tumor showed components of classic hepatic AML, but the central region contained atypical epithelioid components with extremely pleomorphic and hyperchromatic nuclei with frequent mitotic figures. Immunohistochemical analysis revealed that the epithelioid cells were positive for HMB-45 and smooth muscle actin. Furthermore, the atypical epithelioid cells displayed P53 immunoreactivity and mutation at exon 7 for p53. The tumor showed a typical monoclonal pattern but no loss of heterozygosity or microsatellite instability. Markedly atypical epithelioid cells with vascular invasion, distant metastasis, and fatal outcome were interpreted as malignant characteristics of hepatic AML. It is suggested that large tumor size, pleomorphic nuclei with high proliferation activity, and P53 immunoreactivity may predict the existence of malignant transformation of hepatic AML.     

Multiple giant angiomyolipomas with a polygonal epithelioid cell component in tuberous sclerosis: An autopsy case report

A recent case of angiomyolipoma (AML) with a prominent Component of polygonal epithelioid cells is described. A 27-yearoid Japanese male with tuberous sclerosis presented with massive abdominal tumors increasing progressively in size. The patient died of respiratory disturbance and the autopsy revealed massive tumors in the bilateral kidneys, liver and lymph nodes, subependymal giant cell glioma of the brain and lymphangiomyomatosis of the lungs. The giant tumors were an unusual type of AML with a component of polygonal epithelioid cells, which showed a hepatocel-lular carcinoma-like pattern in some areas. Smooth muscle components comprising spindle cells, short or plump spindle cells and polygonal epithelioid cells frequently exhibited positive staining for HMB-45 but negative staining for epithelial cell markers. The unusual AML presented in this case was thought to be of low-grade malignancy and slow growing. it has been suggested that angiomyollpomas with diffuse areas of epithelioid cell component are potentially malignant. Immunostalnings positive for HMB-45 but negative for epithelial cell markers are considered to be useful in differentiating AML with polygonal epithelioid cell component from other tumors, especially from renal cell carcinoma and hepatocellular carcinoma.     

Modified fine‐needle aspiration technique for diagnosis of granulomatous skin lesions with special reference to leprosy and cutaneous tuberculosis

Skin infections are commonly assessed by slit skin or scrape methods. Fine‐needle aspiration biopsy (FNAB) is highly effective especially with blanching of skin to ensure good yield and reduced bleeding. The aim of this study was to assess usefulness of cytology, especially modified FNAB technique, in diagnosis of leprosy and cutaneous tuberculosis and to identify specific cytological characteristics for diagnosis and classification. The study was conducted on 40 patients—25 cases of leprosy and 15 cases of cutaneous tuberculosis. Smears were prepared using modified FNAB technique, slit skin, and scrape methods (depending on type of lesion). Cytological diagnosis was confirmed by histopathology where the Ridley‐Jopling system was used to classify cases of leprosy. A similar attempt was made for diagnosis and classification of leprosy on cytology. Diagnoses rendered by both modalities were compared to assess the efficacy of cytological examination. Cytological diagnosis was made in 23 cases of leprosy and 12 cases of cutaneous tuberculosis. The smears showed good cellularity. A broad division into tuberculoid and lepromatous leprosy could be made fairly accurately on cytology. Maximum agreement among clinical, cytological, and histopathological diagnosis was observed in cases of tuberculoid leprosy. Smears of cutaneous tuberculosis were characterized by epithelioid cell granulomas with caseation. Overall accuracy of diagnosis was 92% in leprosy and 80% in tuberculosis. FNAB is an inexpensive and accurate procedure for diagnosis of leprosy and cutaneous tuberculosis. The modified technique yields good results. However, clinical correlation, acid‐fast staining, and culture are essential as they provide valuable supportive information. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Fine needle aspiration biopsy of renal mucinous tubular and spindle cell carcinoma: Report of two cases

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare renal tumor. Here we report two cases of MTSCC which were initially evaluated by fine needle aspiration biopsy (FNAB) and followed by surgical resection of the tumors. The cytomorphologic features of MTSCC were characterized by aggregates of relatively uniform, predominantly oval to spindle cells intermixed with abundant metachromatic myxoid matrix. Only rare epithelioid tumor cells with vacuolated cytoplasm were present. Immunohistochemically, the tumor cells were positive for CK7, CK19, CD10, vimentin, E‐cadherin, alpha‐methyl CoA racemase, and negative for CK903 and CK20. EMA and carbonic anhydrase IX immunoreactivity was seen in one of the two cases. Multiple chromosomal losses involving chromosomes 1, 2, 17 and likely chromosome 7 were revealed by fluorescence in situ hybridization (FISH). These cytomorphologic, immunophenotypic, and cytogenetic features were helpful for including this entity in the differential diagnosis of renal cell carcinomas. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Hepatic epithelioid angiomyolipoma with an unusual pathologic appearance: expanding the morphologic spectrum

Hepatic epithelioid angiomyolipoma (AML) is a rare lesion that is characteristically composed of a predominant or exclusive population of epithelioid cells coexpressing melanocytic and myogenic markers. The cystic variant of epithelioid AML is exceedingly uncommon. In this study, we present the clinicopathological features of a case of hepatic epithelioid AML with remarkable cystic degeneration in a 34-year-old female as well as with a literature review. A magnetic resonance imaging scan revealed a well-defined 30 cm × 25 cm hepatic mass. Sectioning of the well-defined mass revealed a non-encapsulated tumor that was multiloculated with amorphous necrotic tissue and hemorrhagic fluid. The inner cystic wall was rough and brownish-black in color. Microscopically, the tumor largely consisted of epithelioid cells that comprised approximately 95% of the total neoplastic components but also contained some spindle myoid cells, mature fat, and a thick-walled vasculature. Both intracellular and extracellular hyaline globules were frequently identified. Necrosis and invasive growth patterns were also present. By immunohistochemistry, spindle-epithelioid neoplastic cells were variably positive for Melan-A, HMB45, and SMA but were uniformly negative for epithelial and hepatocytic markers. This is the third report of a cystic AML in liver. The patient was followed for 71 months without any evidence of metastasis or recurrence.     

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 mimicking true lipoma of the liver: report of two cases

Hepatic angiomyolipoma (AML) is very rare and only about 80 cases have been reported. The tumor is fundamentally heterogeneously composed of the three tissue components of blood vessels, smooth muscle cells (SMC), and fat cells. Two cases of hepatic AML are reported here, both of which are histologically composed predominantly of a fat cell element and resembled true lipoma (lipomatous AML). However, careful examination of both tumors revealed the presence of a small amount of epithelioid SMC, especially around blood vessels. Immunohistochemical study using monoclonal antibody for melanoma (HMB-45) clearly revealed a small amount of HMB-45-positive SMC around the blood vessels and scattered in the diffuse fat cell growth in both tumors. Since no liver tissue components or primary liver tumors are reactive with HMB-45 except AML cells, the presence of HMB-45-positive cells within the tumor clearly established the diagnosis of hepatic AML. Any fatty tumor or focal fatty lesion of the liver that superficially resemble true lipomas should be tested for the presence of HMB-45-positive SMC in the tumor to differentiate it from AML.     

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.     

Epithelioid angiosarcoma: A neoplasm with potential diagnostic challenges

Epithelioid angiosarcomas are extremely rare tumors associated with poor prognosis and early metastases. Its epithelioid cytomorphology and limited vasoformation make it difficult to distinguish from more common malignancies, such as, carcinoma. This can be a potential diagnostic pitfall for the cytopathologist. In this report, the patient is a 24‐year‐old man presenting with testicular pain, a pelvic mass, and innumerable liver nodules. Immediate interpretation of the needle core biopsies of the pelvic mass and liver lesions initially favored a poorly differentiated adenocarcinoma. Unusual positive immunohistochemical stains for CD30 and CK7 ultimately led the investigation toward a tumor of mesenchymal origin. Further, immunohistochemical evaluation demonstrated positive CD31 and Factor VIII staining and established the final diagnosis of epithelioid angiosarcoma. The tumor cells were negative for CD34, CK20, alpha‐fetoprotein, placental‐like alkaline phosphatase, hepatocyte paraffin 1, polyclonal carcinoembryonic antigen, CD10, CA‐125, prostate‐specific antigen, and prostatic acid phosphatase. This case is reported to illustrate the importance of considering the diagnosis of epithelioid angiosarcoma when encountering an “epithelioid” neoplasm particularly with unusual immunoreactivity for CK7 and CD30. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Estrogen receptor is significantly associated with the epithelioid variants of renal angiomyolipoma: a clinicopathological and immunohistochemical study of 67 cases

Perivascular epithelioid cells (PEC) in angiomyolipoma (AML) were recently proposed to be its most common progenitor cells. Histologically, triphasic components were present in various proportions, but were overwhelmingly myogenic in epithelioid variants of AML. Despite histological discrimination, the immunophenotypic profiles between triphasic and epithelioid AML have never been compared. The aim of the present study was to clarify the identity of PEC by using immunoreactivity to estrogen receptor (ER), progesterone receptor (PR), bcl-2 and placenta alkaline phosphatase (PLAP), and to use this information to compare triphasic and epithelioid AML. A total of 33 out of 67 cases of renal angiomyolipoma that underwent surgery were reviewed over the period 1998-2003. Two cases were associated with tuberous sclerosis. Ten patients had other malignant tumors, and three patients had a nodal extension. Immunohistochemistry showed that bcl-2 (59.4%), PLAP (46.9%), HMB-45 (100%) was predominantly localized around vessels. The stem cell markers were absolutely negative in all AML types. The estrogen receptors were positive in 14 cases (42.4%) and the progesterone receptors were positive in five cases. Bcl-2 and both female sex hormone receptors were significantly more frequent in the epithelioid variant of AML than in the triphasic type. Perivascular epithelioid cells express bcl-2, ER, PR and PLAP, and ER could be partly associated with myogenic proliferation.     

Renal epithelioid angiomyolipoma with epithelial cysts: demonstration of Melan A and HMB45 positivity in the cystic epithelial lining

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.     

A case of multiple macronodular hepatic tuberculosis difficult to differentiate from hepatocellular carcinoma with intrahepatic metastasis: CT-guided fine needle aspiration biopsy confirmed the diagnosis

Multiple macronodular hepatic tuberculosis is difficult to be differentiated from hepatocellular carcinoma with intrahepatic metastasis in clinical practice, especially when hepatitis B with or without liver cirrhosis coexists with it. Herein, we report a 30-year-old man with a 10-year history of hepatitis B and a family medical history of hepatocellular carcinoma related with hepatitis B that was finally diagnosed as multiple macronodular hepatic tuberculosis. Abdominal B-mode ultrasonography (US) and plain computed tomography (CT) revealed multiple unequal-sized nodules in the liver. CT-guided fine needle aspiration biopsy (FNAB) of the liver demonstrated a caseating granuloma with lymphocytes, multinucleate giant cells and epithelioid cells compatible with the diagnosis of tuberculosis and no hepatoma cells were detected. Thus, the diagnosis of hepatic tuberculosis was confirmed and hepatocellular carcinoma with intrahepatic metastasis was excluded.     

Multifocal angiomyolipoma affecting the liver and lung without tuberous sclerosis

The occurrence of angiomyolipoma (AML) in tissue other than the kidney is uncommon, as is multiple AML developing exclusively in organs other than the kidney. This report describes a case in which AML occurred multifocally in the liver and lung, but spared the kidney, and which might have been associated with tuberous sclerosis complex (TSC). A Japanese woman underwent a partial hepatectomy for a suspected malignant liver tumour at the age of 57. The tumour consisted predominantly of a trabecular arrangement of myoid cells with a sinusoidal pattern and inflammatory cell infiltration, and was diagnosed as a primary liver AML by HMB-45 immunoreactivity. Five years later, multiple nodules were found in both lungs, for which video assisted thoracic surgery was performed. The tumour showed a mixture of epithelioid cells containing HMB-45 positive material and mature lipocytes, and was subsequently diagnosed as AML. Molecular analysis of both lesions showed no allelic loss of the TSC1 and TSC2 regions. Molecular analysis of the tumours ruled out an association with TSC, and both liver and lung lesions displayed benign histological features, so that these were probably multifocal lesions of AML without TSC.     

Sclerosing variant of epithelioid angiomyolipoma

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.     

Epithelioid angiomyolipoma of the liver: a clinicopathologic study of 5 cases

This study aimed to study the clinicopathologic characteristics of epithelioid angiomyolipoma, a variant of angiomyolipoma (AML) in the liver; and to discuss the diagnostic challenges. Five cases of primary liver epithelioid AML were retrieved from our archives from January 2003 to October 2012. The clinicopathologic features of each case were retrospectively reviewed. All 5 patients were female, with age ranging from 36 to 70 years (median, 41 years). The size of the tumor ranged from 1.2 to 25 cm. Histologically, the tumor comprised polygonal cells with granular eosinophilic cytoplasm and accompanied by immunohistochemical expression of HMB-45 ± Melan-A. Variations in growth pattern and cytology were observed. Estrogen receptor was negative in all 5 cases. None showed cytologic atypia, coagulative necrosis, increased mitotic count, or vascular invasion. Epithelioid AML is an uncommon primary liver tumor with a female predominance. The size of the tumor can be variable. This tumor might impose diagnostic difficulty both clinically and histologically. Immunohistochemical staining with melanocytic markers is a promising means to confirm the pathologic diagnosis. A careful assessment of aggressive histologic features is recommended to stratify the risk of aggressive behavior of this tumor.     

Metastatic retroperitoneal epithelioid angiomyolipoma

Angiomyolipoma (AML) is a rare benign neoplasm that usually arises in the kidneys, but may rarely originate in sites such as the retroperitoneum, liver and bone. It is characterised by an intimate admixture of blood vessels, smooth muscle and fat. This multiphasic composition allows for its recognition on ultrasound and CT scan examination. Metastases are exceedingly uncommon, and only one other case of metastatic extrarenal AML exists in the literature. Histological variants of AML such as epithelioid angiomyolipoma (EAML) are considered to be locally aggressive. A unique case of an EAML of the retroperitoneum that metastasised to the liver and bone in an 80-year-old woman is described.     

Efficacy of fine‐needle aspiration biopsy in diagnosis of breast cancer: A retrospective study of 303 cases in Bahrain

Breast cancer is a leading cause of death in many countries worldwide and breast lesions remain a common diagnostic dilemma. Fine‐needle aspiration biopsy (FNAB) has been suggested as the most important, first line, minimally invasive measure in the management of patients with breast lesions. The aim of this study is to evaluate the efficacy of FNAB in patients with breast lesions by comparing the diagnostic accuracy of cytology results with that of the definitive histological examination outcome and also to investigate the added value of a single aspirator experience to the overall diagnostic precision and compared with the internationally published results. A retrospective study of 303 breast FNAB samples were carried out by a single experienced cytopathologist with complete comparison records. The prevalence of positive cytologic diagnosis for the breast cancer was determined to be 20.4%. The overall diagnostic accuracy of FNAB was 97.9%, with a specificity and sensitivity of 98.3 and 96.5%, respectively. The overall positive and negative predictive values were determined to be 93.2 and 99.2%, respectively. In addition, the sensitivity was comparable in cases that have been attempted by palpation‐guided sampling compared with those aspirations that were carried out under US guidance. Results from this study confirm that FNAB biopsies performed and reported by a dedicated, single, skilled cytopathologist are highly effective in diagnosis of breast lesions and reliable in differentiating benign and malignant breast lesions with an overall high efficacy in a specialized laboratory‐based FNAB clinic. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Angiomyolipoma: Immunohistochemical and Ultrastructural Study of 14 Cases

Angiomyolipoma (AML) is a mesenchymal neoplasm of unclear histogenesis. In addition to varying amounts of smooth muscle, adipose tissue, and blood vessels, it contains a population of clear or pale eosinophilic epithelioid cells often arranged around blood vessels. Various phenotypes of AML have been described: leiomyoma-like, lipoma-like, epithelioid, and atypical. AMLs show consistent immunopositivity for HMB-45. This has been associated with the ultrastructural observation of melanosome-like structures in rare instances. In the present study, 14 AMLs from 13 patients were analyzed by electron microscopy and immunohistochemistry to determine the appearance and nature of cells composing AMLs. Overlap between cell types (spindle smooth muscle cells, epithelioid cells, and adipocytes) was found by both electron microscopy and immunohistochemistry. Melanosomes were found in 7 tumors. The cell of origin remains mysterious. Nevertheless, the study demonstrates that the AML is likely derived from a single cell that shares homology with the pericyte.     

Leishmania lymphadenitis diagnosed by fine-needle aspiration biopsy

A case of Leishmania lymphadenitis which presented clinically as an isolated left laterocervical lymph node is described. Diagnosis was made by fine-needle aspiration biopsy (FNAB), as in other cases previously reported. The material obtained yielded abundant histiocytes, multinucleated giant cells, and epithelioid micro-granulomas with Leishman-Donovan pathognomic bodies in the cytoplasm of cells, together with free forms of the parasite. This paper comments on the main differential diagnoses to be considered in our region when faced with granulomatous adenitis and the role of FNAB in the identification of this parasite in endemic areas.