VCL-ALK renal cell carcinoma in children with sickle-cell trait: the eighth sickle-cell nephropathy?

We report the third case of a renal cell carcinoma bearing a fusion of the vinculin (VCL) and anaplastic lymphoma kinase (ALK) genes. Like the 2 other reported cases, this neoplasm occurred in a young patient (6 y old) with sickle-cell trait and demonstrated distinctive morphologic features including medullary epicenter, discohesive polygonal or spindle-shaped cells with prominent cytoplasmic vacuoles, and prominent lymphocytic infiltrate. The neoplastic cells demonstrated focal membranous labeling for ALK protein by immunohistochemistry, ALK gene rearrangement by fluorescence in situ hybridization, and a specific VCL-ALK gene fusion by reverse transcriptase polymerase chain reaction. VCL-ALK renal cell carcinoma may represent the eighth sickle-cell nephropathy.

Fibrosarcoma-like lipomatous neoplasm: a reappraisal of so-called spindle cell liposarcoma defining a unique lipomatous tumor unrelated to other liposarcomas.

The term "spindle cell liposarcoma" has been applied to liposarcomas (LPSs) composed predominantly or exclusively of spindled cells. These tumors have been considered variants of well-differentiated LPS (WDL), myxoid LPS, and spindle cell lipoma, suggesting that this is a heterogenous group of lesions. Using strict morphologic criteria and molecular and immunohistochemical analyses, we have identified a homogenous group of spindle cell lipomatous tumors, histologically and genetically distinct from other forms of LPS, which we have called "fibrosarcoma-like lipomatous neoplasm." Cases classified as "spindle cell LPS" or "low-grade LPS with spindle cell features" were reviewed. Final selection criteria included: (1) an exclusive low-grade spindle cell component resembling fibrosarcoma; (2) a mixture of bland fibroblastic cells resembling the preadipocyte and early-adipocyte stage of embryonic fat; and (3) molecular-genetic analysis that excluded other forms of lipomatous tumors. Of the initial 25 cases identified, comparative genomic hybridization (CGH) was uninformative in 2 cases; 5 were reclassified as WDL on the basis of molecular data (MDM2 amplification) and 6 as spindle cell lipoma (CGH profiles with a few gains and losses including a constant loss of chromosome 13 and frequent losses of chromosomes 16 and 6). The 12 remaining cases showed flat CGH profiles; of these cases, 11 were negative for DDIT3 gene rearrangements, and 1 result was uninterpretable. Patients ranged in age from 15 to 82 years (mean 50 y); male patients were affected slightly more often (7:5). Tumors arose in the deep (6) and superficial (3) soft tissue of the groin (4), buttock (3), thigh (2), flank (1), shoulder (1), and paratesticular tissue (1) and ranged in size from 2 to 20 cm (mean 7.5 cm). Clinical follow-up in 11 patients (9 mo to 20 y; mean 68 mo) showed no recurrences or metastases. As defined above, "fibrosarcoma-like lipomatous neoplasm" is a unique lipomatous tumor that should be distinguished from WDL/(low-grade) dedifferentiated LPS and myxoid LPS on combined histologic/molecular features because of its better prognosis.

Anatomic tumor location influences the success of contemporary limb-sparing surgery and radiation among adults with soft tissue sarcomas of the extremities.

PURPOSE: To examine the influence of anatomic location in the upper extremity (UE) vs. lower extremity (LE) on the presentation and outcomes of adult soft tissue sarcomas (STS). METHODS AND MATERIALS: From 2001 to 2008, 118 patients underwent limb-sparing surgery (LSS) and external beam radiotherapy (RT) with curative intent for nonrecurrent extremity STS. RT was delivered preoperatively in 96 and postoperatively in 22 patients. Lesions arose in the UE in 28 and in the LE in 90 patients. Patients with UE lesions had smaller tumors (4.5 vs. 9.0 cm, p < 0.01), were more likely to undergo a prior excision (43 vs. 22%, p = 0.03), to have close or positive margins after resection (71 vs. 49%, p = 0.04), and to undergo postoperative RT (32 vs. 14%, p = 0.04). RESULTS: Five-year actuarial local recurrence-free and distant metastasis-free survival rates for the entire group were 85 and 74%, with no difference observed between the UE and LE cohorts. Five-year actuarial probability of wound reoperation rates were 4 vs. 29% (p < 0.01) in the UE and LE respectively. Thigh lesions accounted for 84% of the required wound reoperations. The distribution of tumors within the anterior, medial, and posterior thigh compartments was 51%, 26%, and 23%. Subset analysis by compartment showed no difference in the probability of wound reoperation between the anterior and medial/posterior compartments (29 vs. 30%, p = 0.68). Neurolysis was performed during resection in (15%, 5%, and 67%, p < 0.01) of tumors in the anterior, medial, and posterior compartments. CONCLUSIONS: Tumors in the UE and LE differ significantly with respect to size and management details. The anatomy of the UE poses technical impediments to an R0 resection. Thigh tumors are associated with higher wound reoperation rates. Tumor resection in the posterior thigh compartment is more likely to result in nerve injury. A better understanding of the inherent differences between tumors in various extremity sites will assist in individualizing treatment.

Skeletal Metastasis.

The most commonly diagnosed tumor in the skeleton represents metastatic disease. Metastatic carcinoma should be the first consideration in older patients with atypical radiologic findings or clinical features suggestive of a bone lesion. The primary goal in the setting of skeletal metastasis is usually palliation.

Epithelioid Lesions.

Epithelioid variants have been described for most mesenchymal tumors, including leiomyosarcoma, pleomorphic liposarcoma, epithelioid fibrous histiocytoma, and myxofibrosarcoma. Soft tissue tumors that commonly show epithelioid morphology include epithelioid vascular lesions, epithelioid sarcoma, sclerosing epithelioid fibrosarcoma, and epithelioid malignant peripheral nerve sheath tumor. Many of the entities described in this review were originally described as "simulating carcinoma" or "often mistaken for carcinoma" and this pitfall should be considered when evaluating epithelioid lesions in soft tissue. Many epithelioid soft tissue tumors express epithelial antigens to a varying degree and an immunohistochemical panel is essential for correct classification.

Pediatric cutaneous angiosarcomas: a clinicopathologic study of 10 cases.

Cutaneous angiosarcomas are rare tumors, which predominantly arise in the sun-exposed skin of the head and neck of adult and elderly patients. Rarely, these tumors can be seen in children. We identified cutaneous angiosarcomas in 10 children and assessed clinical (patient age, tumor site, tumor size, and tumor focality) and histologic features including growth pattern (vasoformative vs. solid), mitotic rate (mitotic figures per 10 high power field), necrosis (present vs. absent), and cell shape (epithelioid vs. nonepithelioid). Tumors predominated in the lower extremities (6 of 10) of female patients (2 male and 8 female); age at diagnosis ranged from 1.5 months to 15 years. Four patients had preexisting conditions: congenital hemihypertrophy of the contralateral limb, the Aicardi syndrome, congenital lymphedema, and congenital hemangioma treated with radiation therapy. Tumors were located in the lower extremity (6), flank (1), elbow (1), and buccal mucosa (1), and ranged in size from 0.6 to 6.5 cm. Eight cases showed predominantly epithelioid morphology, 1 case showed mixed epithelioid and spindled morphology and 1 case was entirely spindled. Mitotic activity ranged from 1 to 55 mitotic figures per 10 high power field. Necrosis was seen in 5 cases. Clinical follow-up was obtained for 9 patients: 4 died of disease (range, 12 to 49 mo; mean, 25 mo) and 5 patients were alive without disease (18 mo to 28 y). Five patients had metastatic disease; sites of involvement included the lung, soft tissue, lymph node, pleura, liver, and bone. Cutaneous angiosarcomas in children are rare tumors, which are commonly associated with a preexisting condition, suggesting a greater role for genetics as opposed to environmental factors in the pathogenesis of these tumors.

Angiosarcomas arising in the viscera and soft tissue of children and young adults: a clinicopathologic study of 15 cases.

Angiosarcomas are rare tumors that predominantly affect adult and elderly patients and pursue an aggressive clinical course with high mortality. Although angiosarcomas are well described in a variety of clinical settings, they have been incompletely characterized. We identified 15 high-grade angiosarcomas arising from the viscera and soft tissue of patients 21 years old and younger from institutional and consultation files. Both clinical (patient age, tumor site, tumor size, tumor focality) and histologic features including growth pattern (vasoformative vs. solid), nuclear grade (high vs. low), mitotic rate (mitotic figures/10 high-power fields), necrosis (present vs. absent), and cell shape (epithelioid vs. nonepithelioid) were assessed. Tumors arose in both sexes (8 males; 7 females); age at diagnosis ranged from 3 months to 19 years (mean, 10 y, 5 mo; median, 11 y). Tumors were located in the mediastinum (7), visceral organs (2 in liver, 1 in spleen), breast (2), mesentery (1), pelvis (1), and deep soft tissue of upper extremity (1). Tumor size was documented for 8 patients (range 3.5 to 13 cm; mean 8.1 cm). Eight cases showed epithelioid morphology and 7 cases were primarily spindled. Of 8 cases assessed for podoplanin expression by immunohistochemistry, 7 were negative and 1 was positive. Clinical follow-up was obtained for all patients: 10 (67%) died of disease (range, 27 mo to 11 y; mean, 6 y 8 mo) and 4 patients were alive without disease (range, 27 to 132 mo; mean, 79 mo). Although extremely rare, angiosarcomas do affect children and young adults and this diagnosis should be considered in atypical vascular tumors occurring in the mediastinum and those with brisk mitotic activity and/or necrosis.

Epithelioid hemangioendothelioma of soft tissue: a proposal for risk stratification based on 49 cases.

Epithelioid hemangioendothelioma (EHE) of soft tissue is a distinctive vascular tumor that has been variously considered a tumor of borderline malignancy and low-grade angiosarcoma. The majority of cases are associated with low mortality, but some metastasize and cause patient death. We analyzed 49 cases of EHE to determine if a method for stratifying risk for mortality could be developed. Fifty-one cases of EHE diagnosed during the period of 1989 and 2005 were retrieved. Tumors were evaluated with respect to location, size, cytologic atypia, mitotic activity, tumor cell spindling, and necrosis. Follow-up information was obtained for all cases. For actuarial analysis, disease-specific overall survival was evaluated using univariate and multivariable analysis. Most tumors occurred in adults (range, 9 to 93 y) and affected women predominantly (21 M:28 F). They developed in the head and neck (6), extremities (32), mediastinum (4), trunk (4), genitals (2), and retroperitoneum (1) and ranged in size from 0.5 to 18 cm. Clinical follow-up was obtained for all patients and ranged from 1.5 to 170 months (mean, 57.9 mo); 31 patients were alive without disease, 5 patients were alive with disease, 9 patients died of disease and 4 died of other causes. Overall 5-year disease-specific survival was 81%. Eleven patients (22%) had metastatic disease affecting lung (6), lymph node (4), liver (2), and bone, retroperitoneum, and soft tissue (1 each). Two patients had metastases to multiple sites. Treatment modality was known for 46 patients: 31 were treated surgically and 15 were treated with surgery and chemotherapy and/or radiation therapy. By univariate analysis, mitotic activity and size were associated with higher mortality (P=0.007 and 0.004, respectively). By multivariable analysis, increasing mitotic activity (P=0.00827, hazard ratio 10.03) and size (P=0.01, hazard ratio 2.26) were associated with decreased survival. Tumor site, cytologic atypia, the presence of necrosis, and tumor spindling were not significant. Those tumors with >3 mitotic figures/50 high power fields and size >3.0 cm had the worst prognosis (P=0.0002). Patients with high-risk tumors had a 5-year disease-specific survival of 59%; no patients with low-risk tumors died. In conclusion, we report that EHE can be stratified into 2 risk groups with markedly different clinical courses.

Atypical vascular lesions after surgery and radiation of the breast: a clinicopathologic study of 32 cases analyzing histologic heterogeneity and association with angiosarcoma.

We report the clinicopathologic study of 32 cases of atypical vascular lesions (AVLs) after surgery and radiation of the breast, which were referred to us in consultation over a 17-year period. The patients, all women, ranged in age from 41 to 95 years (mean 61 y). The lesions developed within the radiation field from 1 to 12 years (median 6.0 y) after therapy. They occurred as one (n=18) or more (n=10) flesh-colored papules or erythematous patches/plaques ranging in size from 1 to 60 mm (mean 8.0 mm, median 4.0 mm). Tumors could be divided into 2 histologic types: a lymphatic type (LT) (n=22) and a vascular type (VT) (n=10). LT AVLs consisted predominantly of thin-walled, variably anastomosing lymphatic vessels that were usually confined to the superficial dermis but occasionally extended into the deep dermis and even subcutis. The VT (n=10) typically consisted of small, irregularly dispersed, often blood-filled, pericyte-invested, capillary-sized vessels involving the superficial or deep dermis. VTs were often associated with extravasated erythrocytes, hemosiderin, and a surrounding minor LT component. In 4 cases, endothelial atypia, consisting of nuclear and nucleolar enlargement, was noted. Follow-up of 21 patients with LT AVLs (1 to 106 mo; mean 47 mo) disclosed recurrence/additional lesions in 6, all of whom had additional surgery. Of the 21 patients, 17 are alive without disease, 1 is alive with disease, 1 died of breast carcinoma, 1 died of unknown causes, and 1 showed progressive histologic changes in the AVLs over a period of 5 years resulting in a well-differentiated angiosarcoma. Follow-up in 8 patients with VT AVL (2 to 181 mo; mean 40 mo) disclosed that 6 were alive and well, but 2 of the 4 patients whose lesions displayed endothelial atypia had additional complications. One patient underwent a mastectomy that revealed extensive residual AVL and the second developed a high-grade angiosarcoma after 14 months. We conclude that AVLs encompass a wider spectrum of changes than previously appreciated, ranging from superficial lymphatic proliferations to more complex lymphatic and capillary vascular lesions. There seems to be an association of AVL with angiosarcoma that differs depending on the histologic features, with the VT AVLs having the higher risk. In the 2 patients who developed angiosarcoma, morphologic evidence suggested AVLs to be a precursor rather than simply a risk factor. Future outcome and management studies should take into account these differences.

Aggressive (epithelioid) osteoblastoma arising in soft tissue.

Aggressive (epithelioid) osteoblastoma arising in soft tissue has never been described. It is important to differentiate this benign osteoblastoma, a potentially locally aggressive tumor, from extraskeletal osteosarcoma. This report describes an aggressive (epithelioid) osteoblastoma arising in a focus of heterotopic ossification in the axilla of a 21-year-old man.

Epstein-Barr virus-associated epithelial and mesenchymal neoplasms.

Epstein-Barr virus (EBV) is a ubiquitous human pathogen that usually maintains a harmonious relationship with its host. Rarely, this host-virus balance is perturbed, causing a diverse group of malignancies in both immunocompetent and immunosuppressed patients. In addition to its role in hematologic malignancies (Burkitt lymphoma, subsets of Hodgkin and T-cell lymphomas, posttransplant lymphomas), EBV has been implicated in both epithelial (undifferentiated nasopharyngeal carcinoma, a subset of gastric adenocarcinomas) and mesenchymal (EBV-associated smooth muscle tumor, inflammatory pseudotumor-like follicular dendritic cell tumor) neoplasms. This review will focus on EBV-associated epithelial and mesenchymal neoplasms.

Sporadic cutaneous angiosarcomas: a proposal for risk stratification based on 69 cases.

Angiosarcomas have traditionally been considered high-grade lesions for which histologic features and grading have played no role in prognostication and, consequently, they have been excluded from the American Joint Committee on Cancer staging system. We have, therefore, analyzed 69 cutaneous angiosarcomas seen in consultation and not associated with lymphedema or prior radiation therapy to determine if a combination of histologic and clinical parameters could be used to differentiate indolent from aggressive tumors. The clinical features analyzed included patient age, location, size, depth, and focality of the lesion; the histologic features studied included pattern of growth (vasoformative vs. solid), nuclear grade (high vs. low), necrosis (present/absent), cell type (epithelioid or spindled), extent of inflammatory infiltrate (minimal vs. marked), and mitotic rate. Lesions occurred on the head/neck (49), extremities (15), and trunk (5) of adults (21 to 94 y) and predominated in males (41 males; 28 females). Tumors ranged in size from 0.3 to 15 cm (average 3.1 cm) and involved the papillary (n=9), reticular (n=16), or deep dermis/ subcutis (n=30). They could be predominantly vasoformative (n=28) to solid (greater than 50% solid, n=41). Most lesions were of high (n=65) as opposed to low (n=4) nuclear grade, were mitotically active (0 to 99/10 high power fields), and occasionally displayed necrosis (n=14) and epithelioid features (n=21). Inflammatory infiltrates were minimal in most cases. Follow-up information was obtained for all patients. Recurrences developed in 18 patients (26%) and metastasis in 15 (22%) to the following sites: lung (6), lymph node (7), liver (2), bone (2), and parotid gland (1). Forty-seven patients died (30 of disease) and 22 were alive at last known follow-up (range, 16 to 158 mo; mean, 65; median, 36). Five-year disease-specific survival was 48%. By univariate analysis only older age, anatomic site, necrosis, and epithelioid features correlated with increased mortality. Tumors were stratified into low (n=41) or high (n=28) risk groups based on necrosis and/or epithelioid features. By multivariable analysis, high-risk group (hazard ratio 4.07, P=0.0004) and age >70 (hazard ratio 2.79, P=0.012) were associated with increased mortality, and tumor depth (P=0.048) correlated with the risk of local recurrence. The high-risk group had a significantly worse prognosis than the low-risk group with 3-year survival of 24% and 77%, respectively. No patients with high-risk features survived 5 years. In conclusion, we report that a combination of clinical and histologic features allows stratification of angiosarcoma patients into 2 risk groups that are strongly associated with marked differences in clinical course. These features seem to diminish in importance with increased tumor size and are probably most useful in tumors less than 5 cm in maximum dimension.

Sarcomas arising in Paget disease of bone: a clinicopathologic analysis of 70 cases.

CONTEXT: Sarcomatous transformation is a rare complication of Paget disease of bone. Prognosis in patients with other types of sarcomas arising in bone has improved in the last several decades because of therapeutic advances. However, because of the rarity of Paget sarcoma, outcome studies in these patients are limited. OBJECTIVE: To determine whether prognosis for Paget sarcoma has improved. DESIGN: Seventy cases of sarcomas arising in the setting of Paget disease were collected, and the histologic and clinical findings were reviewed. Clinical follow-up was obtained in 67 cases. RESULTS: Sarcoma arising in Paget disease tended to arise in older men (46 men, 24 women; age range, 31-88 years; mean age, 66 years) and predominated in the axial skeleton (n = 37), especially in the pelvis. Thirty-three patients had a clinical history of Paget disease ranging in duration from 16 months to 30 years (mean, 15 years). No significant difference in incidence between monostotic (n = 33) and polyostotic (n = 36) disease was noted. Most tumors were osteosarcomas (88%). All tumors were high grade. Follow-up information was obtained in 67 of 70 cases (range of follow-up, 1-252 months). Survival ranged from 1 month to 20 years, with a 5-year survival rate of 10%. CONCLUSIONS: Prognosis remains poor in patients with Paget sarcoma. There is no significant correlation between the number of bones involved with Paget disease or the duration of disease and development of Paget sarcoma. Poor prognosis in Paget sarcoma is unrelated to site or stage at presentation.

Epithelioid and epithelial neoplasms of bone.

CONTEXT: Epithelioid and epithelial neoplasms seen in bone are rare and include epithelioid variants of vascular lesions, osteoblastoma, osteosarcoma, chordoma, and chondroblastoma as well as adamantinoma and metastatic carcinoma. OBJECTIVE: To provide an overview of tumors with epithelioid histology and address the clinical context and diagnostic issues. DATA SOURCES: Pertinent literature is reviewed with emphasis on recent and controversial issues. CONCLUSIONS: The differential diagnosis in epithelioid/epithelial lesions of bone is limited. The primary consideration in many cases is distinguishing primary from metastatic lesions.

Estrogen receptor-beta expression in extraabdominal fibromatoses: an analysis of 40 cases.

BACKGROUND: Early experiments using ligand-binding assays demonstrated the presence of estrogen receptor (ER) in fibromatoses. These findings were not confirmed by later studies using immunohistochemical analysis. METHODS: To verify the expression of ERs in fibromatosis as well as to clarify the inconsistency between radioligand and early immunohistochemical studies, the authors examined a series of 40 extraabdominal fibromatoses using antibodies raised against ERbeta. RESULTS: All 40 cases of extraabdominal fibromatosis were at least focally positive for ERbeta. Thirty-three of 40 (83%) displayed 3+ (>50%) expression, 5 of 40 (12%) were 2+ (11-50%), and 2 of 40 (5%) cases showed 1+ (<10%) expression. All cases were negative for ERalpha. CONCLUSIONS: Although extraabdominal fibromatosis does not express ERalpha, there appears to be nearly uniform expression of ERbeta. This finding clarifies discrepancies in the literature regarding estrogen expression in fibromatosis, and provides a biological mechanism for the action of antiestrogenic compounds in the treatment of fibromatosis. Estrogen antagonists may have a role in the treatment of refractory or recurrent extraabdominal fibromatoses.

Epstein-Barr virus-associated smooth muscle tumors are distinctive mesenchymal tumors reflecting multiple infection events: a clinicopathologic and molecular analysis of 29 tumors from 19 patients.

Epstein-Barr virus-associated smooth muscle tumors (EBV-SMT) are rare lesions that occur in immunocompromised patients. Because they have not been fully characterized pathologically or at the molecular level, we have studied 29 tumors from 19 patients, the largest series to date. Cases coded as EBV-SMT were identified in 19 patients from consultation files and from the renal transplant database at Singapore General Hospital. EBV-SMT occurred in adults (mean age 39 years; range, 21-57 years) and predominantly affected males (12 male, 7 female). Causes of immunocompromise were renal transplantation (10), AIDS (8), and steroid therapy (1). Tumors were located in soft tissue (5), lung (5), liver (4), and miscellaneous sites (15). In 13 patients (68%), the tumors were multiple. Infection with EBV was confirmed in all cases by in situ hybridization for EBV early RNAs (EBER). EBV-SMT were typically well-differentiated smooth muscle tumors with little atypia and usually a low level of mitotic activity. Unlike classic leiomyosarcomas, they lacked significant pleomorphism but frequently displayed primitive round cell areas and prominent intratumoral T lymphocytes. No consistent relationship between histologic features and clinical outcome was noted. All expressed actin (29 of 29) and less frequently desmin (14 of 26). Multiple tumors in a given patient were clonally distinct as assessed by the long terminal repeat region of the virus, supporting the view that multifocal tumors arise from multiple infection events rather than from metastasis. Strain typing by analysis of the EBNA-3C gene confirmed the presence of EBV type 2. Two of four tumors assessed were positive for a 30-bp deletion in the LMP1 gene. EBV copy number per cell ranged greatly between patients and between tumors from the same patient. Follow-up information was available in 18 of 19 patients (mean, 25 months; range, 1-105 months). Fifteen patients were alive: 11 with disease and 4 without. Three patients died, 1 due to disease. We conclude that EBV-SMT are histologically distinct from classic soft tissue smooth muscle tumors, are not readily evaluated by means of conventional histologic criteria, and in the case of multifocal tumors are the result of multiple infection events rather than metastasis. EBV-2 can transform smooth muscle cells, independent of the presence of the LMP1 deletion associated with greater virulence.

Increased expression of S100A6 is associated with decreased metastasis and inhibition of cell migration and anchorage independent growth in human osteosarcoma.

While most osteosarcoma patients have metastatic or micrometastatic lesions, less than 15% of them have clinically detectable metastatic diseases at presentation. To identify potential markers that may predict osteosarcoma metastasis, we analyzed the expression of S100A6 in 50 osteosarcoma cases and found that 84% of the analyzed specimens stained positive for S100A6. There is a trend towards decreased clinically evident metastasis with increased S100A6 staining. Overexpression of S100A6 in osteosarcoma cells decreases cell motility and anchorage independent growth on collagen gels. Our findings provide evidence that, while S100A6 is commonly overexpressed in human osteosarcoma, loss of its expression correlates with a metastatic phenotype.

Paraganglioma-like dermal melanocytic tumor: a unique entity distinct from cellular blue nevus, clear cell sarcoma, and cutaneous melanoma.

We are reporting a previously undescribed primary dermal melanocytic tumor identified by reviewing all dermal melanocytic tumors referred in consultation that did not qualify histologically as a previously described entity. From these cases, 8 were remarkably similar. We termed them "paraganglioma-like dermal melanocytic tumor" (PDMT) based on their nested growth pattern. This term is used descriptively and does not imply any histogenetic or biologic similarity to true paraganglioma. PDMT is primarily a tumor of the extremities of adult females (18-53 years, mean 35 years; males 2; females 6) which present as a dermal nodule (range, 0.5-4.2 cm; mean, 1.4 cm) composed of nests of clear to amphophilic oval cells separated by delicate fibrous strands. Nuclear atypia was mild and mitotic activity low (1-4 mitoses/10 HPF). Melanin was not obvious on light microscopy. Tumors expressed S-100 protein (8 of 8), Melan-A (4 of 8), HMB-45 (8 of 8), and microphthalmia transcription factor (8 of 8) and lacked pancytokeratin (8 of 8) and smooth muscle actin (8 of 8). FISH analysis of 5 cases revealed an intact EWS gene locus, supporting absence of the clear cell sarcoma 12;22 translocation. Follow-up information in 8 patients (range, 35-92 months; mean, 54 months) indicated that all were alive without disease. PDMT comprises a clinically and pathologically unique subtype of dermal melanocytic tumors. Our study suggests a benign course, although a lesion of low malignant potential cannot be excluded.