Cytologic features of pigmented atypical meningioma mimicking melanoma on intraoperative crush preparations

Pigmented tumors rarely arise in the meninges, and when they do, these are mainly melanocytomas or melanomas. We describe the cytologic findings of atypical meningioma with intratumoral hemosiderin pigment mistaken for spindle cell melanoma in a 33‐year‐old male patient during intraoperative consultation. Preoperative radiologic images revealed a cystic meningeal mass with intratumoral hemorrhage. The crush preparation demonstrated cellular smears of syncytial clusters as well as fascicles of large pleomorphic spindle cells with discrete cytoplasmic brown pigment. Detection of cytoplasmic brown pigment and a preponderance of large spindle cells with nuclear pleomorphism led to a diagnosis of spindle cell melanoma on intraoperative cytology. Histopathologic examination displayed high cellularity, nuclear pleomorphism with prominent nucleoli, and foci of spontaneous necrosis. In addition, there were areas showing classic meningotheliomatous meningioma features. Altogether, the histologic findings were consistent with atypical meningioma. The cytoplasmic pigment in the tumor cells was confirmed to be hemosiderin using special stains and immunohistochemistry. To the best of our knowledge, this is the first case report describing cytomorphology of atypical pigmented meningioma. We discuss the differential diagnosis in intraoperative cytology and a possible mechanism related to intratumoral hemosiderin deposition in meningiomas. Diagn. Cytopathol. 2015;43:149–152. © 2014 Wiley Periodicals, Inc.     

Exaggerated pigmented granulomatous reaction to the artificial joint implant mimics metastatic melanoma

Total joint replacement is a common orthopedic procedure. An artificial joint implant may fail due to mechanical mishap and a granulomatous reaction can be induced by the artificial joint debris after the mechanical failure. We report a case of an exaggerated pigmented granulomatous tissue response to metallic artificial joint implant debris in a 72-yr-old male that was mistaken for metastatic melanoma. The mass was soft, pigmented, ill-defined, and located in the right inguinal region. Fine-needle aspiration revealed numerous black-pigment laden cells. The cellular features were frequently obscured by the heavy pigmentation. Occasional cells exhibited atypia and prominent nucleoli. There were also abundant extracellular irregular small black particles dispersed in the background. The diagnosis of melanoma involving a lymph node was made. Since there was no prior history of melanoma, it was presumed that this represented metastatic melanoma from an unknown primary. A subsequent exploration of the groin was performed with the intent to resect the disease. At exploration, the mass was found to be contiguous with the hip joint and the frozen section of the mass revealed no evidence of melanoma. The final tissue diagnosis confirmed the frozen section report and showed a granulomatous reaction. This report underscores the diagnostic dilemma associated with the exaggerated pigmented granulomatous reaction due to an artificial prosthesis.     

A case report of anthracosilicotic spindle-cell pseudotumor of mediastinal lymph node: cytologic diagnosis by endoscopic ultrasound-guided fine-needle aspiration

Pigmented spindle-cell tumors of the lymph nodes have a broad differential diagnosis, including both benign and malignant neoplasms. Here, we report a case of a pigmented spindle-cell lesion in a mediastinal lymph node mimicking a spindle-cell melanoma on fine-needle aspiration cytology. Smears showed atypical polygonal and spindle cells with bland nuclear features and abundant cytoplasmic anthracotic pigment. Immunohistochemistry was negative for melanoma markers, but showed positivity for histiocyte markers. Polarization microscopy revealed minute birefringent intracellular crystals consistent with silica. Electron microscopy was confirmatory and a diagnosis of anthracosilicotic spindle-cell pseudotumor was made. To the best of our knowledge, fine-needle aspiration cytology findings of this lesion have not been reported.     

Malignant pigmented clear cell epithelioid tumor of the kidney: clear cell ("sugar") tumor versus malignant melanoma

A 73-year-old woman presented with an hemorrhagic kidney tumor initially interpreted as a renal cell carcinoma (RCC). A retroperitoneal recurrence infiltrating the duodenal wall was made up of clear cells, some of which contained Fontana-Masson positive pigment, immunopositive for HMB-45, S-100 protein, actin, and vimentin. The same immunohistochemical profile was retrospectively reproduced in the kidney tumor, where melanosomes were also found ultrastructurally. Lipomatous differentiation was not observed. There was no history of malignant melanoma (MM), or stigmata of tuberous sclerosis. The patient died of disease 5 years after the initial diagnosis. This neoplasm can be considered as a malignant, pigmented, clear-cell epithelioid variant of angiomyolipoma, or "sugar" tumor of the kidney, with the peculiarity of having a previously unreported component of pigmented cells visible on light microscopy. This finding raises the possibility that the exceptional cases of MM reported in renal parenchyma may be pigmented variants of epithelioid angiomyolipoma rather than true MM.     

Epithelioid angiomyolipoma of kidney with atypical nuclear features and intranuclear inclusions on cytology

Described herein are the cytological findings of epithelioid angiomyolipoma (EAML) of the kidney with atypical nuclear features mistaken for renal cell carcinoma (RCC) in a 61‐year‐old male patient. Aspirates from this large renal mass were cellular and showed epithelioid cell clusters with focally crowded nuclei showing moderate anisonucleosis, small nucleoli, and prominent eosinophilic intranuclear inclusions. Failure to recognize the scanty adipose tissue component and preponderance of epithelioid cells with nuclear pleomorphism lead to a diagnosis of RCC on cytology. On histology, the tumor was essentially composed of epithelioid and spindle cells that showed the typical immunoprofile of an angiomyolipoma and only occasional foci of typical AML were seen. The hilar lymph node was involved in contiguity. However, in view of lack of obvious features of malignancy, the tumor was labeled as EAML with atypical features. Immunocytochemistry on the destained cytology aspirates revealed strong smooth muscle actin staining of all cells. To conclude, EAML can mimic a RCC. In such instances, lack of arborizing vasculature, absence of cytoplasmic fatty vacoulation, crowded nuclei with intranuclear inclusions, and lack of prominent nucleoli along with typical immunophenotype of EAML may assist in the cytology diagnosis. Diagn. Cytopathol. 2011;39:278–282. © 2010 Wiley‐Liss, Inc.     

EBUS‐FNA of a station seven lymph node: An unusual presentation of a young nonsmoker male with hemoptysis and subcarinal lymphadenopathy

Endobronchial ultrasound‐guided fine needle aspiration (EBUS‐FNA) is a safe and minimally invasive bronchoscopic technique that allows both visualization and cytologic sampling with a high diagnostic yield in a patient with mediastinal lymphadenopathy. Besides the most common indication of staging for a patient with a primary lung carcinoma, EBUS‐FNA can be used to identify benign infectious and noninfectious processes as well as lymphoma and malignancy of unknown primary. Triaging of procured specimen for diagnostic, prognostic, and therapeutic ancillary studies requires appropriate clinical information at the time of rapid on site evaluation (ROSE) of smears. This case report demonstrates a young, previously healthy nonsmoker presenting clinically with cough, hemoptysis, and a 1.7 cm enlarged subcarinal lymph node by imaging. EBUS‐FNA obtained smears from the lymph node revealed a pleomorphic population of smaller cells with a low nuclear to cytoplasmic ratio and prominent nucleoli, and larger cells had nuclei with bizarre shapes, mitoses, multinucleation, enlarged nucleoli, and pigmentation in a background of lymphocytes. The cytomorphologic and immunohistochemical workup of this case confirmed the unexpected diagnosis of metastatic melanoma. This result was a complete surprise to the clinical team managing the patient and prompted a thorough clinical workup. Subcarinal lymphadenopathy with metastatic malignant melanoma as the cause is rare. This case report highlights how ROSE and appropriate triaging of specimen were crucial in appropriately working up this case. We also survey the literature to review the reported unusual presentations of metastatic melanoma. Diagn. Cytopathol. 2015;43:238–242. © 2014 Wiley Periodicals, Inc.     

Intranuclear inclusions in a case of pigmented villonodular synovitis of the ankle

Pigmented villonodular synovitis (PVNS) is a proliferative disorder of the synovial lining of the joints. Although the cytological findings of this disorder have been described in the literature, there is no mention of intranuclear cytoplasmic inclusions in this entity. A 65-yr-old woman presented with a painful swelling on the ankle. In addition to other characteristic findings of PVNS, we found the presence of intranuclear cytoplasmic inclusions in the fine-needle aspiration (FNA) smears. The characteristic cytological findings of abundant mononuclear cells occurring singly and in papillary clusters, multinucleated giant cells, and hemosiderin deposition should aid in the diagnosis of PVNS and in its differentiation from melanoma and other soft tissue sarcomas, even in the presence of uncommon features such as intranuclear inclusions.     

Epithelioid Monophasic Synovial Sarcoma

A 47-year-old man presented with a soft tissue mass of the distal right thigh near the knee. The tumor was highly vascular with epithelioid tumor cells growing in a peritheliomatous pattern, suggesting a soft tissue glomus tumor. Yet many tumor cells contained hemosiderin pigment and formed papillary structures suggestive of pigmented villonodular synovitis. Tumor cells were cytologically bland, and there was minimal mitotic activity. The tumor cells were strongly immunoreactive for cytokeratin, however, and contained true desmosomes, gland lumina, microvilli, tonofilaments, and well-developed basal lamina. These findings plus the absence perinuclear aggregates of intermediate filaments rule out malignant rhabdoid tumor and epithelioid sarcoma. Also, magnetic resonance imaging revealed no other lesions to suggest metastatic carcinoma. Thus this tumor appears to be a predominantly epithelioid form of monophasic synovial sarcoma. Recognition of this variant of synovial sarcoma is important for prognostication and therapeutic decision making because some studies indicate that this variant of synovial sarcoma follows a relatively benign clinical course.     

Congenital malignant melanoma--a case report

Herein reported is a case of congenital malignant melanoma in a premature male baby from a 25-year-old healthy mother who was found to have hydramnios at the 29th week of gestation. The pregnancy was interrupted because of a large posterior neck mass detected by ultrasonography. The large neck mass of the baby was a malignant melanoma involving deep dermis and subcutaneous tissue. The skin over the mass showed a large area of pigmentation with hairs and the pigmentation involved the occipital scalp and posterior neck. Microscopically, the tumor cells were monotonous and showed polygonal and epithelioid appearance with prominent nucleoli indicative of malignant melanoma of a minimal deviation variety. Neither junctional components nor benign dermal nevus cells were noted. There were no distant metastasis or underlying leptomeningeal melanosis. This tumor is presumed to have developed from either preexisted congenital giant pigmented nevus with loss of benign components or de novo origin.     

Primary synovial epithelioid sarcoma of the knee: distinctly unusual location leading to its confusion with pigmented villonodular synovitis

Epithelioid sarcoma (ES) is a rare malignant soft tissue tumor occurring in the distal extremities of young adults and is characterized histologically by nodules of epithelioid cells showing central necrosis. Intra‐articular ES is extremely rare; only four cases have been reported, but their radiologic and histologic documentation of intra‐articular origin have been imprecise. We report the first radiologically and histologically well‐documented case of primary synovial ES. A 59‐year‐old woman presented with pain followed by swelling of her right knee for 6 months. MRI revealed an entirely intra‐articular nodular synovial mass in the lateral part of the right knee joint in a background of diffusely thickened synovium. Synovectomy was performed under the clinical impression of pigmented villonodular synovitis (PVNS), a diagnosis erroneously confirmed by the reporting pathologist. The tumor rapidly recurred 3 months afterward and the diagnosis of primary synovial ES was made. Despite above‐knee amputation, the tumor continued to spread proximally to the retroperitoneum. She developed multiple lung metastases and died 20 months after initial presentation. The nodular aggregates of tumor cells with central necrosis resulted in diffuse polypoid synovial thickening mimicking tuberculous synovitis and PVNS. The tumor cells showed positive staining for EMA, CK19, CD34, and complete loss of INI1 staining, establishing the diagnosis of primary synovial ES. The ES spread from the synovium to and along the joint capsule, and then extra‐articularly into the soft tissue surrounding the knee joint, with lymphovascular permeation. Such pattern of spread calls for radical surgical excision as the treatment of choice.     

Epithelioid angiosarcoma: a brief diagnostic review and differential diagnosis

Epithelioid angiosarcoma is a highly aggressive endothelial cell malignancy, most commonly arising in the deep soft tissues, but a variety of primary sites, including the adrenals, thyroid, skin, and bone, are encountered. On hematoxylin-eosin-stained sections, the pathologist encounters sheets of large, mildly to moderately pleomorphic epithelioid cells, with abundant eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli. Obvious vasoformative foci may not be present, creating confusion with metastatic carcinomas, malignant mesothelioma, melanoma, anaplastic lymphoma, epithelioid peripheral nerve sheath malignancies, and epithelioid sarcoma. Moreover, malignancies with apparent vascular differentiation must be distinguished from less aggressive vascular neoplasms, including epithelioid hemangioendothelioma. Given the range of clinical presentation, the diversity of primary sites, and the nonspecific initial histopathologic appearance, here we review the histologic findings and immunohistochemical profiles of epithelioid angiosarcoma and neoplasms in its differential diagnosis.     

Primary anorectal mucosal melanoma detected by anorectal cytology

The detection of primary anorectal melanoma on anal cytology is a rare and challenging diagnosis. We report a case where anorectal cytology showed isolated malignant cells with oval nuclei, prominent nucleoli, and elongated wispy cytoplasmic projections. There was no evidence of squamous dysplasia or melanin pigment identified. To the best of our knowledge, this is the first reported case of a primary anorectal melanoma detected in anorectal cytology. Detection of malignancies other than squamous cell carcinoma can be seen on anorectal cytology and should be considered when there is no evidence of anal intraepithelial neoplasia. Diagn. Cytopathol. 2017;45:452–455. © 2017 Wiley Periodicals, Inc.     

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

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

Benign atypical junctional melanocytic hyperplasia associated with intradermal nevi: a common finding that may be confused with melanoma in situ.

Over the past few years, consultation cases thought to represent melanoma in situ have been received that consisted of otherwise normal intradermal nevi with an abnormal but benign junctional proliferation of melanocytes that we have termed benign atypical junctional melanocytic hyperplasia. In order to evaluate the incidence of this feature, 400 cases of intradermal nevi were reviewed. Of these, 25 (6.2%) qualified for inclusion, making this a rather common phenomenon. Clinically, patient ages ranged from 18 to 64 years (mean, 35 years), with a male to female ratio of 1:1. Face (40%) and back (32%) were the most common locations. Histologically, the lesions were predominantly dome-shaped with an intradermal component consisting of conventional nevus cells. Most importantly, each lesion exhibited prominent individual nevomelanocytic cells dispersed at uneven intervals along the dermoepidermal junction in insufficient numbers to be considered compound nevi. The cells exhibited abundant pale to clear cytoplasm, an increased nuclear:cytoplasmic ratio, and often exhibited prominent nucleoli. However, these lesions could be distinguished from melanoma in situ by the lack of several features including lateral spread, upward epidermal migration, marked cytologic atypia, finely granular "smoky" melanin pigment, mitotic figures, and a subjacent host inflammatory response. All cases behaved in a benign fashion. Although benign atypical junctional melanocytic hyperplasia is a relatively common histological curiosity, it is a potential pitfall in the diagnosis of pigmented lesions.     

Epithelioid hemangioendothelioma

Summary The epithelioid hemangioendothelioma (EHE) is a rare vascular tumour of borderline malignancy, first described as a separate entity in 1982 by Weiss and Enzinger. The abundant cytoplasm of endothelial cells mimiking epithelioid appearances, prominent cytoplasmic vacuolization and barely perceptible lumina even in reticulin stains may result in EHE being mistaken for a signet ring cell carcinoma. In our case, difficulties in differential diagnosis were enhanced by the location of the tumour within an inguinal lymph node. The usefulness of FVIIIR:Ag- and UEA I- histochemistry in ascertaining the endothelial nature of this tumour is demonstrated, in correlation with electron microscopic data. The different reaction sites of these markers are striking and typical: FVIIIR: Ag displays a granular or diffuse cytoplasmic reaction, whereas UEA I provides a linear staining of vacuoles and luminal surfaces.     

Melanoma with signet-ring cells in a peritoneal effusion

Melanoma may occasionally give rise to a malignant effusion and when this occurs it can present a challenging differential diagnosis. We present such a patient who developed a peritoneal effusion. Cytologic examination of the peritoneal fluid revealed individual malignant cells with prominent cytoplasmic vacuoles raising the possibility of a signet-ring cell adenocarcinoma. Immunohistochemical studies were indicative of a malignant melanoma. in this case we believe that the cytoplasmic vacuoles may be a degenerative phenomenon and as such may represent another mechanism for the development of a signet-ring morphology in malignant melanoma. © Wiley-Liss, Inc.     

Epithelioid angiomyolipoma: a morphologically distinct variant that mimics a variety of intra-abdominal neoplasms

This review examines the histopathologic, immunohistochemical, ultrastructural, and molecular biologic features of epithelioid angiomyolipoma (EAML), with an emphasis on the differential diagnosis of intra-abdominal EAML. Epithelioid angiomyolipoma is an uncommon mesenchymal tumor with malignant potential, frequently associated with tuberous sclerosis complex. Histologically, EAML is characterized by sheets or nests of large polygonal epithelioid cells with abundant eosinophilic or occasionally clear cytoplasm, often with prominent nucleoli, and EAML may include multinucleated and markedly pleomorphic forms. As these tumors share a distinctive perivascular epithelioid cell phenotype, they belong to the PEComa tumor family. Nearly all EAMLs show immunoreactivity for both melanocytic and myoid markers. Ultrastructurally, EAMLs show evidence of melanogenesis by the presence of premelanosomes. Epithelioid angiomyolipoma can pose significant diagnostic challenges as it mimics morphologically a variety of neoplasms including renal cell carcinoma, renal oncocytoma, adrenal cortical neoplasm, epithelioid smooth muscle tumor, epithelioid peripheral nerve sheath tumor, epithelioid gastrointestinal stromal tumor, epithelioid melanoma, hepatoblastoma, and hepatocellular carcinoma. The variation in immunophenotype in these tumors requires a prudent use of immunohistochemistry, which may occasionally need complementation by electron microscopy to establish the correct diagnosis.     

Epitheloidzellige und hyperpigmentierte melanozytäre Tumoren

Spindle cell and epithelioid cell differentiation occur in both benign and malignant hyperpigmented melanocytic lesions. Reed nevus is characterized by compact, sharply circumscribed junctional cellular nests composed of slender hyperpigmented melanocytes shaped like spindle cells. Deep penetrating nevus is characterized by a diffuse dermal proliferation composed of small nests and fascicles of pale ovoid and epithelioid melanocytes. Cellular blue nevi often have a characteristic hourglass or dumbbell shape, with sharply circumscribed elongated nests and fascicles of pale, densely layered ovoid melanocytes and adjacent melanophages. Epithelioid blue nevus is characterized by large epithelioid melanocytes with abundant cytoplasm and melanin often concentrated to some degree in the cell membrane. Animal-type melanoma is a particularly hyperpigmented variant of melanoma in which large melanophages predominate and there are varying proportions of melamin-rich spindle-shaped and large atypical epithelioid melanocytes. Morphologically, pigmented epithelioid melanocytoma combines characteristics of both animal-type melanoma and pigmented epithelioid nevus. Malignant melanoma may occur in conjunction with a preexistent blue nevus. Malignant blue nevus is now regarded as a malignant melanoma mimicking a blue nevus in structure and pattern. It is therefore of paramount importance to view multiple mitoses within a cellular blue nevus-like proliferation as an alarm signal as they are usually indicators of a malignant melanoma.     

Correlation of histologic architectural and cytoplasmic features with nuclear atypia in atypical (dysplastic) nevomelanocytic nevi

The dysplastic nevus in nonfamilial melanoma is a clinicopathologic entity consistently demonstrating an eightfold or greater association with malignant melanoma. The present report quantifies the relationship between nuclear atypia and 16 architectural and cytoplasmic features in 153 pigmented nevi removed from a similar number of patients with newly diagnosed nonfamilial melanoma. All lesions were evaluated by one dermatopathologist, and most lesions were reviewed by a second dermatopathologist. Nuclear atypia of nevomelanocytes was defined as at least three of the following: nuclear enlargement, pleomorphism, hyperchromatism, and prominent nucleoli easily observed throughout each lesion. Seventeen percent of the total nevi had such atypia. On univariate analysis, 11 parameters (lentiginous hyperplasia of the epidermis, basal melanocytic hyperplasia, junctional nest disarray, fusion [bridging] of theques, suprabasal melanocytes, lymphoid response, prominent vascularity, fibroplasia, abundant cytoplasm, "dusty" cytoplasm, and large melanin granules) showed an association with nuclear atypia (P less than .05). However, on multivariate analysis only five parameters continued to be important: basal melanocytic hyperplasia, junctional nest disarray, melanophages (inverse correlation), prominent vascularity, and large melanin granules. These data support the idea that multiple histopathologic characteristics, correlating objectively with nuclear atypia, are important for the diagnosis of dysplastic nevi. In our view, the minimal essential histologic criteria for dysplastic nevi based on these findings include nuclear atypia and abnormal patterns of intraepidermal nevomelanocytic proliferation (ie, basal melanocytic hyperplasia and/or junctional nest disarray).     

A case of amelanotic spindle-cell melanoma presenting as metastases to breast and axillary lymph node: diagnosis by FNA cytology

Metastatic neoplasms to the breast are relatively rare. Spindle-cell lesions of the breast are also uncommon. Here we present a case of fine-needle aspiration (FNA) of an amelanotic, spindle-cell melanoma metastatic to the breast and axillary lymph node. The patient was a 47-yr-old female who presented with a right breast mass, left axillary adenopathy, and a pigmented skin lesion on the back. FNA of the right breast and left axilla showed malignant, nonpigmented spindle cells that were weakly positive for HMB-45 on immunocytochemistry. The skin biopsy showed a pigmented malignant melanoma with epithelioid features, and also weak positivity for HMB-45. Although malignant melanoma is one of the more common tumors to metastasize to the breast, this is the first known case that showed exclusive spindle-cell morphology. History and physical examination were crucial in making the correct FNA diagnosis. The cytologic differential diagnosis of spindle-cell tumors of breast and the discordant morphology between the primary and metastatic melanotic lesions observed in this case are discussed.