NUT carcinoma, an under-recognized malignancy: a clinicopathologic and molecular series of 6 cases showing a subset of patients with better prognosis and a rare ZNF532::NUTM1 fusion.

NUT carcinoma (NC) is a rare malignancy with aggressive clinical behavior, defined by rearrangements involving the NUTM1 gene locus. This entity is often under-recognized and its diagnosis may be challenging. In this study, we describe a subset of patients that, despite the molecularly proven diagnosis of NC, show improved outcomes. In addition, we describe one case with the novel ZNF532::NUTM1 fusion. All cases of NC diagnosed from 2013 to 2022 in our department were retrieved. FISH using dual color bring-together probes and next-generation sequencing assay were performed to characterize the fusions involving NUTM1. Among 6 patients identified, 5 were men with a median age of 35.6 years. Four patients had primary tumors in the head and neck region (2 ethmoid sinus, 1 parotid gland, and 1 lacrimal gland); 1 in the mediastinum, and another presented with a femoral bone tumor. In all cases, the initial diagnoses were not NC. The cases showed different morphological patterns, including monomorphic, rhabdoid, and pleomorphic appearances. One case showed a pseudopapillary pattern. By immunohistochemistry, all tumors showed squamous differentiation and ≥50% of neoplastic cells with nuclear positivity for NUT antibody. One case expressed WT1 (C-terminus) and other showed chromogranin positivity. Genetic study revealed a BRD4::NUTM1 fusion in all head and neck cases, BRD3::NUTM1 in mediastinum case, and ZNF532::NUTM1 fusion in the femur bone case. They were treated with surgical resection plus chemotherapy and radiotherapy. The median overall survival was 23.11 months (1.6-83.3 months) and the median disease-free survival was 14.86 months (0-54.4 months). The patients with longer overall survival were one with a lacrimal gland primary (83.3 months) and other with a parotid lesion (31.9 months). Both patients were primarily treated with complete surgical resection. Anatomic location may be directly related to the overall survival in NC cases. Resectability of the lesion is also an important factor related to survival. Pathologists should include NC in the differential diagnosis of any poorly differentiated and undifferentiated monomorphic malignancy, regardless of its anatomic location.

Central odontogenic fibroma in association with brown tumor of hyperparathyroidism in a patient with neurofibromatosis type 1.

We present a patient with bone abnormalities and a myriad of lesions secondary to his redeveloping renal failure and neurofibromatosis type 1 (NF1). A 21-year-old male renal transplant recipient with NF1 presented with painless masses and large, irregular radiolucent lesions in the maxilla and mandible. After histologic examination, the lesion was diagnosed as a central odontogenic fibroma (COdF) in association with a central giant cell lesion, most consistent with brown tumor of hyperparathyroidism. The bone changes were interpreted to be highly suggestive of renal osteodystrophy. Around 30 cases of hybrid central giant cell granuloma-like lesion in association with central odontogenic fibroma have been reported. This, to our knowledge, is the first reported case of brown tumor in association with COdF. Our case provides further evidence of the giant cell component as the initiating entity in these hybrid lesions.

Osteofibrous Dysplasia and Adamantinoma.

For decades, the diagnosis, treatment, and even pathogenesis of the osteofibrous dysplasia/osteofibrous dysplasia-like adamantinoma/classic adamantinoma spectrum of neoplasms have been controversial. Herein, we discuss and illustrate the radiographic and histologic spectrum, differential diagnoses, unifying chromosomal and molecular abnormalities, and current controversies and treatment recommendations for each entity.

Palmar and plantar fibromatosis: a review.

Palmar fibromatosis (Dupuytren disease/contracture) is the most common type of fibromatosis, defined as a benign proliferation of fibroblasts and myofibroblasts. The disease process is most common in white, middle-aged and older men occurring at the distal palmar crease leading to nodules and contracture, which in many cases recur after surgical treatment. In a similar process, plantar fibromatosis (Ledderhose disease) is a proliferation of fibroblasts and myofibroblasts on the plantar aponeurosis of mostly middle-aged patients that may lead to painful nodules but usually does not lead to contracture. Both processes are histologically similar, composed of a bland cellular proliferation of spindle cells with a bluish appearance and with a variable amount of background collagen, depending on the age of the lesion. The etiology of both lesions is still uncertain, while treatment ranges from observation to surgery, with some pharmacologic agents being investigated with mixed success. In this paper we provide an overview of both processes with regards to clinical and radiologic findings, pathophysiology, diagnosis, treatment, and prognosis.

PAX8 Distinguishes Diffuse Large B-Cell Lymphoma Mimicking Sarcoma.

PAX8 is important for embryogenesis of the thyroid, Müllerian system, and upper urinary/renal tract, and expression of PAX8 has been described in carcinomas from each of these sites. The sensitivity and specificity of the polyclonal PAX8 antibody in a large cohort of epithelial tumors as well as lymphomas have been previously determined, the latter because polyclonal PAX8 is known to be immunoreactive in nonneoplastic B-cell lymphocytes which are often used as the positive internal control for immunohistochemistry. In this case report, PAX8 was a diagnostic clue for revising a previous diagnosis of unclassified high grade sarcoma to diffuse large B-cell lymphoma. This case report demonstrates a pitfall for PAX8 immunoreactivity and acts as a reminder that lymphoma should be included in the differential diagnosis of a PAX8 positive, epithelial cell marker negative tumor of unknown primary origin.

Atypical Spindle Cell Lipomatous Tumor: Clinicopathologic Characterization of 232 Cases Demonstrating a Morphologic Spectrum.

The classification of atypical adipocytic neoplasms with spindle cell features remains challenging. To better define this category of low-grade lipomatous neoplasms, we present herein the clinical, histologic, and immunohistochemical characteristics of a large series of 232 atypical spindle cell lipomatous tumors. The lesions affected 140 males and 92 females, at an average age of 54 years (range, 6 to 87 y), clinically presenting as a persistent or enlarging mass with a median size of 5 cm. The anatomic distribution of the tumors was wide, predominating in the limbs and limb girdles (147 cases, 63%), mainly in the hands and feet (17% and 11%, respectively), with equal distribution between subcutaneous and deeper locations. Microscopic examination revealed a spectrum of histologic appearances. All cases consisted of a poorly marginated proliferation of mildly atypical spindle cells set in a fibrous or myxoid stroma, with a variably prominent admixed adipocytic component showing variation in adipocyte size and scattered nuclear atypia, frequently with univacuolated or multivacuolated lipoblasts. Tumor cellularity and the relative proportion of the different components were very variable. Tumor margins were often ill defined with invasion into surrounding tissues. Two tumors showed morphologic features reminiscent of dedifferentiation. By immunohistochemistry, the neoplastic spindle cells expressed CD34 (64%), S100 protein (40%) and, less frequently, desmin (23%). Expression of Rb was lost in 57% of cases examined. MDM2 and CDK4 were never coexpressed and FISH for MDM2 amplification was consistently negative, highlighting critical biological differences from atypical lipomatous tumor/dedifferentiated liposarcoma. The morphologic differential diagnosis of atypical spindle cell lipomatous tumor is broad, and includes spindle cell lipoma, diffuse neurofibroma, mammary-type myofibroblastoma, dermatofibrosarcoma protuberans, fat-forming solitary fibrous tumor, and morphologically low-grade malignant peripheral nerve sheath tumor. Most patients underwent surgical excision of the primary mass. With a median follow-up of 4 years (range, 1 mo to 20 y), 87% of patients (63/72) were alive with no evidence of recurrence or metastatic disease. Local recurrence of the tumor was observed in 12% of patients (9 out of 72, multiple in 3 of them) at intervals between 6 months and 17 years after resection of the primary tumor. None of the patients developed tumor metastasis or died of disease. Identification of the neoplastic adipocytic component admixed with spindle cells, and recognition of the range of histologic appearances are key for the diagnosis of atypical spindle cell lipomatous tumor. Whereas the risk of metastatic dissemination is minimal, there is a non-negligible risk for local recurrence (13%) which warrants surgical resection with clear margins whenever feasible.

Vasculites pulmonares: achados morfológicos e diagnóstico diferencial / culites lung: morphological findings and differential diagnosis

As vasculites são um conjunto de entidades clínico-patológicas sistêmicas caracterizadas pela destruição da parede de vasos sanguíneos. O parênquima pulmonar é consistentemente mais afetado por três vasculites em particular: granulomatose de Wegener (ou granulomatose com poliangite), síndrome de Churg-Strauss e poliangite microscópica. Demograficamente, estas doenças inflamatórias afetam adultos de meia idade, e apresentam-se com sinais e sintomas respiratórios, além de sintomas sistêmicos. O diagnósico destas entidades recais na correlação da apresentação clínica e correlação desta com achados radiológicos e morfológicos. O diagnóstico diferencial das três vasculites pulmonares mais comuns é principalmente com infecções granulomatosas, como micobacterioses e infecções fúngicas, linfomas e outras vasculites. Este artigo explora as principais características histopatológicas e o diagnóstico diferencial destas entidades

Vasculitides are a group of systemic diseases characterized by the destruction of the blood vessels walls. The pulmonary parenchyma is consistently affected by three vasculidites in particular, namely, Wegener granulomatosis (or granulomatosis with polyangeitis), Churg-Strauss syndrome and microscopic polyangitis. Demographically toms. The diagnosis of this group of diseases is based on the correlation of the clinical picture with radiologic and morphologic findings. Differential diagnosis is mostly done with granulomatous infectious, such as mycobacteria and fungus, lymphomas and other vasculidites. This article explores the main histopathologic characteristics of these vasculidites as well as their main differential diagnoses

PAX8 and PAX5 are differentially expressed in B-cell and T-cell lymphomas.

AIMS: The purpose of this study was to evaluate the expression patterns of B-cell specific activator protein (BSAP)/PAX5 and PAX8 in a wide variety of B-cell and T-cell neoplasms. METHODS AND RESULTS: A wide range of B-cell and T-cell neoplasms were subjected to immunohistochemical staining with antibodies against BSAP/PAX5 and PAX8 (polyclonal, pPAX8; monoclonal, mPAX8). Ten non-neoplastic lymph node specimens were examined with the same panel. All of the tested neoplastic and non-neoplastic B-cells reacted with the BSAP/PAX5 and pPAX8 antibodies, but did not show reactivity with the mPAX8 antibody. All tested T-cell neoplasms were negative using the BSAP/PAX5, pPAX8 and mPAX8 antibodies. CONCLUSIONS: This is the first study to show the absence of reactivity to an mPAX8 antibody in an expanded panel of B-cell lymphomas as well as in a variety of T-cell neoplasms. In contrast to the mPAX8 antibody, the pPAX8 antibody shows nuclear positivity in non-neoplastic B cells and mature B-cell neoplasms; however, this expression is probably a result of cross-reactivity with PAX5. Given that many laboratories use the pPAX8 antibody, a clear understanding of the differential staining patterns is necessary. The differential diagnosis of a B-cell lymphoma should be entertained when a pPAX8-positive, epithelial marker-negative neoplasm of uncertain primary origin is encountered.

Cutaneous radiation-associated angiosarcoma of the breast: poor prognosis in a rare secondary malignancy.

BACKGROUND: Cutaneous radiation-associated angiosarcoma of the breast (CRAASBr) is a rare complication of radiation therapy (RT) administered for primary breast cancer treatment. Although case series have provided clinical and histological descriptions of this disease, to our knowledge, none have identified trends in presentation and treatments that may contribute to outcomes. METHODS: Demographic, clinical, histopathologic, and outcomes data for all patients presenting with CRAASBr for treatment or consultation at our institution from 1987 to 2009 were reviewed. RESULTS: We identified 33 patients (median age at CRAASBr presentation 71.3 years, range 43.1-87.2 years; median latency period 73.5 months, range 39.6-148.5 months). The most common presentation was breast skin ecchymosis (55 %). In four patients, initial biopsy demonstrated atypical vascular lesions suspicious for, but not diagnostic of, angiosarcoma. All patients underwent mastectomy. Median local recurrence-free survival (LRFS), recurrence-free survival (RFS), and overall survival (OS) rates were 18.2, 13.0, and 48.5 months, respectively. Patients who underwent resection of all irradiated breast skin as part of the mastectomy trended toward a better median LRFS (80.8 vs. 10.0 months, p = 0.065), RFS (72.6 vs. 10.0 months, p = 0.098), and OS (not achieved vs. 29.0 months, p = 0.054). CONCLUSIONS: CRAASBr is a potentially devastating consequence of RT for breast cancer, with poor LRFS, RFS, and OS rates. Patients with ecchymotic skin lesions require biopsy. Atypical vascular lesions require careful evaluation to rule out CRAASBr. If the diagnosis is confirmed, radical surgery encompassing both the breast parenchyma and the at-risk radiated skin should be performed.

Anaplastic lymphoma kinase-positive large B-cell lymphoma: an underrecognized aggressive lymphoma.

Anaplastic lymphoma kinase-(ALK-) positive large B-cell lymphoma (ALK+ LBCL) is a rare, aggressive tumor characterized by an immunoblastic or plasmablastic morphologic appearance, expression of ALK, CD138, CD45, EMA, and often IgA by immunohistochemistry, and characteristic chromosomal translocations or rearrangements involving the ALK locus. The morphologic and immunophenotypic overlap of this tumor with other hematologic and nonhematologic malignancies may result in misdiagnosis. The tumor has been identified in both pediatric and adult populations and demonstrates a male predominance. Presentation is most often nodal, particularly cervical. No association with immunocompromise or geographic location has been recognized. The most common gene rearrangement is between clathrin and ALK (t(2;17)(p23;q23)), resulting in the CLTC-ALK chimeric protein, although other fusions have been described. Response to conventional chemotherapy is poor. The recent introduction of the small molecule ALK inhibitor, crizotinib, may provide a potential new therapeutic option for patients with this disease.

Recurrence patterns and survival for patients with intermediate- and high-grade myxofibrosarcoma.

PURPOSE: Myxofibrosarcoma (MFS) is a rare sarcoma with a predilection for multiple local recurrences (LR), for which optimal treatment has not been defined. We reviewed our experience to determine the impact of surgery and radiation therapy (RT) on pattern of recurrence, limb salvage, and overall survival (OS). METHODS AND MATERIALS: Between 1995 and 2005, 36 patients with localized intermediate- or high-grade MFS were treated at our institution. Data on clinicopathologic features, treatments, and patient outcomes were reviewed and analyzed. RESULTS: Median age was 72.5 years (range, 42-96 years). Median tumor size was 7.5 cm, and 34 tumors (94%) were high grade. All patients underwent surgery at our institution, including re-resections in 20 patients (56%) after initial surgery elsewhere. Margins were microscopically positive in 9 patients (25%). RT was given to 28 patients (78%) pre - and/or postoperatively. After a median follow-up of 3.5 years (range, 0.4-12.4 years), 11 patients (31%) developed LR. There were no significant predictors for LR on univariate analysis, including margin status or use of RT. Limb salvage was ultimately achieved in only 5 of 11 LRs (45%) because of multiple subsequent LRs. Distant recurrence (DR) occurred in 6 patients (17%). Median and 4-year OS were 96 months and 65%, respectively. Seven patients (19%) died of tumor-related causes, 6 of whom had DRs. On univariate analysis, tumor size was associated with OS. CONCLUSIONS: Despite aggressive surgery and RT, intermediate- and high-grade MFS are associated with a high rate of LR that adversely affects limb preservation. More aggressive local treatment strategies are necessary.

Vascular Lesions of the Breast.

Vascular lesions represent a minority of tumors originating in the breast. The most common entities are benign and include hemangiomas and angiolipomas. Malignant vascular lesions (angiosarcomas) are rare and may be primary or secondary to radiation. Also appreciated in association to radiotherapy is the development of cutaneous atypical vascular lesion affecting the skin of the breast. The relationship of the latter to radiation-associated angiosarcoma is controversial and remains to be elucidated. This article reviews the most likely encountered vascular lesions in the breast, with emphasis on key pathologic diagnostic features and potential diagnostic pitfalls.

Primary angiosarcoma of the breast: clinicopathologic analysis of 49 cases, suggesting that grade is not prognostic.

Mammary angiosarcoma is a rare neoplasm, accounting for about 0.05% of all primary malignancies of the breast. It is currently believed that histologic grading of mammary angiosarcomas plays an important role in prognostication. Forty-nine cases of primary angiosarcoma of the breast were retrieved from our files. Clinical details and follow-up information were obtained from referring pathologists and clinicians, and by chart review. All statistics were performed using Fisher exact test and only P<0.05 was considered significant. Recurrence-free survival and overall survival curves were established using Statistica software version 5.5 (StatSoft Inc). All patients were female with ages ranging from 15 to 74 years (mean 41.5, median 40). Peak incidence was between the ages of 30 and 50 years. All tumors examined were located within breast parenchyma with or without minor cutaneous involvement. The right side was more commonly affected than the left side (66% vs. 29.5%). Tumor was bilateral at presentation in 2 cases (4.5%). Tumor size varied from 0.7 to 25 cm (mean 6.7, median 5). Most patients presented with a palpable, painless mass. Two patients had a history of prior radiation treatment for breast carcinoma. Histologically, primary tumors were graded using Rosen's 3-tier system: 17 tumors (35.4%) as low grade, 17 (35.4%) as intermediate grade, and 14 (29.2%) as high grade. Forty-six patients were treated surgically, 11 underwent chemotherapy, and 12 patients received radiotherapy. Follow-up was available in 41 patients (83.7%, median duration 29 mo). Ten patients (24.4%) showed evidence of local recurrence within 11 to 60 months (median 36) after diagnosis. Twenty-four patients (58.5%) thus far have developed metastases, which were most commonly to lung, liver, skin, and bone. Time interval between diagnosis and metastasis ranged from 2 to 144 months (median 34). Eighteen patients (44%) so far have died of disease and 1 died of presumably disseminated breast carcinoma. Five patients (12.2%) are alive with disease and 15 patients (36.6%) are alive with no evidence of disease. Statistical analysis evaluating correlation between tumor grade and size, and rate of local recurrence, metastasis, and death owing to disease showed no significant difference among tumors of different grades. The median recurrence-free and overall survival rates for the entire cohort were 2.8 and 5.7 years, respectively. In conclusion, mammary angiosarcoma is a rare disease that affects relatively younger patients. This tumor seems to have an overall similar clinical course as other types of angiosarcoma arising in skin or soft tissue; it carries a moderate risk of local recurrence, and a high risk of metastasis and death. In this large series, there is no correlation between histologic grade and patient outcome, more in line with angiosarcomas at other sites.

Diagnosis and management of pleomorphic sarcomas (so-called "MFH") in adults.

The existence of "malignant fibrous histiocytoma" ("MFH") as a distinct entity is controversial. Previously accepted as the most common sarcoma affecting adults, it is now known to comprise a heterogeneous group of tumors without a specific known line of differentiation. Reclassification of many tumors in this group afforded better prognostication, but traditional treatments still apply. Pleomorphic soft tissue tumors for which a line of differentiation is debatable are presently categorized as undifferentiated pleomorphic sarcoma.

The ASC/SIL ratio for cytopathologists as a quality control measure: a follow-up study.

Monitoring the relative frequency of the interpretations of atypical squamous cells (ASC) and squamous intraepithelial lesions (SIL) has been proposed as a quality control measure. To assess its value, an ASC/SIL ratio was calculated every 6 months for 3.5 years, and confidential feedback was provided to 10 cytopathologists (CPs). By using simple regression analysis, we analyzed the initial and final ASC/SIL ratios for individual CPs and for the entire group. The ratio was below the upper benchmark of 3:1 for all but 1 CP during every 6-month period. The ratio for all CPs combined showed a downward trend (from 2.05 to 1.73). The ratio for 6 CPs decreased, and for two of them the decrease was statistically significant. One CP showed a statistically significant increase in the ASC/SIL ratio. The decrease for some CPs likely reflects the salutary effect of confidential feedback and counseling.

Primary cardiac lymphoma: clinical, histologic, immunophenotypic, and genotypic features of 5 cases of a rare disorder.

Primary lymphomas of the heart are rare and frequently are diagnosed at autopsy. Modern imaging technology now permits early diagnosis and treatment. This report describes the clinical, histologic, immunophenotypic, and molecular genetic findings for 5 patients with malignant lymphoma restricted to the cardiac muscle, with or without pericardial involvement. All patients were women, with ages ranging from 40 to 68 years (median 55 y). The right atrium was involved in all cases with the left atrium, right ventricle, and pericardium affected in 1 case each. Clinical presentation included pericardial effusions associated with precordial pain, dyspnea, and bradycardia. Electrocardiographic changes included junctional rhythm, incomplete right bundle branch block and ST and T waves abnormalities, and ST segment elevation and first-degree atrioventricular block with intermittent complete heart block. In all cases, biopsy or resection of the lesion or cytologic examination of the pericardial fluid established a diagnosis. All tumors were of B-cell phenotype and included 4 cases of large cell lymphoma and one unclassifiable small cell lymphoma. In 2 cases, a follicular center cell origin was supported by reactivity of the neoplastic cells for CD10 and bcl-6 and by bcl-2 gene rearrangement by molecular analysis. One patient died shortly after diagnosis due to cerebral infarction. Two patients are alive without disease after chemotherapy with CHOP after 120 and 192 months. One patient underwent chemotherapy with CHOP and rituximab, and shows persistent cardiac involvement by lymphoma but with a decrease in tumor burden at 7 months of follow-up. One patient was lost to follow-up. Clinical outcome is variable; however, early diagnosis in conjunction with effective treatment (surgery and/or chemotherapy) may result in an excellent prognosis. Primary cardiac lymphoma should be included in the differential diagnosis of a right atrial mass.

The controversial nosology of benign nerve sheath tumors: neurofilament protein staining demonstrates intratumoral axons in many sporadic schwannomas.

Schwannomas are benign peripheral nerve sheath tumors believed to be composed purely of cells with ultrastructural features of Schwann cells; these tumors are believed to develop eccentrically from the surface of nerves and not to contain axons, other than immediately beneath the capsule. This concept has recently been disputed in cases associated with neurofibromatosis type 2. The usual presence of intratumoral axons in neurofibromas is said to allow easy distinction from schwannomas. Eighty sporadic schwannomas (20 conventional, 20 cellular, 20 ancient, 10 gastric, and 10 plexiform) were retrieved from the authors' files. Hematoxylin-and-eosin stained slides were reviewed, diagnoses were confirmed and all tumors were stained for S-100 protein and neurofilament protein (NFP). The amount (rare, focal, multifocal, and diffuse) and distribution (central and/or peripheral) of axons within the tumors were analyzed. All tumors were strongly and diffusely positive for S-100 protein (nuclear and cytoplasmic staining). NFP-positive axons were identified in 11 of 20 (55%) conventional schwannomas (2 rare, 4 focal, 3 multifocal, and 2 diffuse; 5 central, 4 peripheral, and 2 central and peripheral) and in 15 of 20 (75%) cellular schwannomas (3 rare, 6 focal, and 6 multifocal; 12 central, 1 peripheral, and 2 central and peripheral). Of the 20 ancient schwannomas, 7 cases (35%) showed intratumoral axons, highlighted by NFP immunostaining (1 rare, 4 focal, 1 multifocal, and 1 diffuse; 4 peripheral, 2 central, and 1 central and peripheral). Most cases of gastric schwannoma showed no evidence of intratumoral axons; 9 cases (90%) were negative for NFP and only 1 case (10%) was positive (focal and central). Seven of 10 cases (70%) of plexiform schwannomas were negative for NFP, whereas only 3 cases (30%) showed positive axons (2 multifocal and 1 focal; 3 central). The unexpected but quite frequent presence of intratumoral axons in schwannomas argues against conventional views of these lesions' pathogenesis as an eccentric encapsulated lesion and raises the possibility that a more diverse cell population, perhaps more closely resembling neurofibromas, may constitute these neoplasms. Although NFP-positive axons were most often present in the conventional and cellular variants of schwannoma, their presence was also observed in a minority of ancient, gastric and plexiform schwannomas. Differentiation between neurofibroma and schwannoma in cases with overlapping cytoarchitectural features should not be based solely on the presence or absence of NFP-positive axons within a given tumor.

HMB-45 and Melan-A are useful in the differential diagnosis between granular cell tumor and malignant melanoma.

Granular cell tumors (GCTs), especially if atypical or malignant, may share cytomorphologic and architectural features with malignant melanoma, when the latter shows granular cell change. In many cases, these neoplasms can be differentiated from each other on histologic grounds, but distinction may sometimes be challenging. By immunohistochemistry, both tumors are strongly positive for S-100 protein and frequently express other nonspecific markers such as CD68, NSE, and NKIC3. In the current study, we reviewed 60 cases of conventional cutaneous, mucosal, and visceral GCT and studied the use of immunoperoxidase staining for the differential diagnosis between malignant melanoma and GCT. Immunohistochemical stains for S-100 protein, A, HMB-45, and microphthalmia transcription factor (MITF) were performed in all cases. All of the tumors were positive for S-100 protein. MITF immunostaining was diffusely positive in 53 (88%) cases, focally positive in three (5%) cases, and negative in four (7%). Fifty-seven (95%) tumors were negative for Melan-A, one case was focally positive, and two cases showed rare positive tumor cells. None of the tumors expressed HMB-45. In conclusion, GCT and malignant melanoma can be reliably differentiated on the basis of immunohistochemical stains in the majority of cases. Although not always positive in malignant melanoma, in this context, HMB-45 expression seems to be 100% specific for the diagnosis of melanoma. Melan-A is slightly less specific, with rare cases of GCT showing focal positivity. MITF is not useful in this differential-93% of the GCTs in our series showed nuclear reactivity for this marker. The latter finding highlights the limited specificity of this antibody in the diagnosis of melanocytic tumors.

Epithelioid variant of myxofibrosarcoma: expanding the clinicomorphologic spectrum of myxofibrosarcoma in a series of 17 cases.

Myxofibrosarcoma (MFS) is one of the most common soft tissue sarcomas of elderly patients and has a predilection for the limbs. Herein, we report a previously undescribed variant of MFS showing epithelioid morphology. Seventeen cases diagnosed as epithelioid MFS were retrieved from the authors' files from among 570 cases of MFS. Hematoxylin and eosin-stained sections were reexamined and immunostains for pan-keratin (15 cases), S-100 protein (15), desmin (15), and alpha-smooth muscle actin (13) were performed. Nine patients were men and 8 were women (age range 43 to 89 y; median 63.5). Fifteen patients presented with a mass, and in 2 of these there was also pain. Duration of symptoms varied from 1 to 24 months (median 3). Tumor size ranged from 2 to 15 cm (median 6.75). In 10 cases, the tumor was located in subcutaneous tissue and in 6 cases it was subfascial. The majority of the tumors were located on the limbs (8 lower extremities and 6 upper extremities) followed by neck (1), scalp (1), and trunk (1). Follow-up was available for 14 patients (range 2 to 240 mo; median 16). Twelve patients were treated by surgery followed by chemotherapy and/or radiation (8 cases). One patient received chemotherapy after an incisional biopsy and 1 patient was treated by surgery alone. Ten patients (71.4%) developed local recurrences. Seven patients (50%) developed metastases to lungs or retroperitoneum. Five patients (35.7%) have died of disease so far. Two patients were lost to follow-up. Morphologically, 14 cases were high grade, 2 were intermediate, and 1 was low grade. Tumors were characterized by a multinodular, infiltrating growth pattern with alternation of hypercellular and hypocellular myxoid areas; the latter showed prominent curvilinear vessels. Neoplastic cells were arranged singly and in small clusters in the myxoid areas or formed sheets in the hypercellular areas, where they showed epithelioid morphology with round nuclei, vesicular chromatin, prominent nucleoli, and moderate amounts of eosinophilic cytoplasm. The epithelioid areas were generally multifocal with admixed areas of conventional MFS. Immunostains were negative for all markers studied. Differential diagnosis included carcinoma, melanoma, myoepithelial carcinoma, pleomorphic liposarcoma, and pleomorphic rhabdomyosarcoma. In conclusion, epithelioid MFS is a rare variant of MFS, accounting for <3% of MFS in consultation material. Its natural history seems more aggressive than usual high-grade MFS, with approximately 70% local recurrence and 50% metastases, even within a relatively short follow-up period.