Briana C. Gleason

Myoepithelial carcinoma of soft tissue in children: an aggressive neoplasm analyzed in a series of 29 cases.

Primary myoepithelial tumors of soft tissue are uncommon, and criteria for malignancy among these neoplasms have only recently been established. Of 51 myoepithelial carcinomas of soft tissue in the literature, 11 occurred in children, 7 of which were included in a previous series of myoepithelial tumors from our group. We have collected an additional 22 cases of myoepithelial carcinoma of soft tissue in the pediatric population, and we describe the detailed clinicopathologic features of all 29 cases herein. There were 15 girls and 14 boys; age at diagnosis ranged from newborn to 17 years (median, 9 y). Sites included extremities (14 cases), trunk (6 cases), viscera (5 cases: 3 mediastinal, 1 retroperitoneal, and 1 intracardiac), and head/neck (4 cases). Histologically, the tumors were heterogeneous, with epithelioid, clear, spindle and/or plasmacytoid cells forming nests, cords or solid sheets in a myxoid or hyalinized stroma. Epithelioid cells predominated in the majority of cases (27 of 29; 93%) and in 10 cases (34%), tumor cells focally had scant cytoplasm with round cell morphology. The mitotic rate ranged from <1 to 68 per 10 high power fields (median, 8), and tumor necrosis was present in 14 cases. At least 1 broad-spectrum cytokeratin was positive in all tumors [CAM5.2 in 17 of 18 (94%), AE1/AE3 in 15 of 20 (75%), and PAN-K in 14 of 21 (67%)], and EMA was positive in 19 of 29 cases (66%). Either S100 or GFAP was positive in all but 4 cases [S100 in 21 of 29 (72%) and GFAP in 15 of 28 (54%)]. Clinical follow-up in 23 cases revealed that 9 patients had local recurrences (53% of the 17 patients who underwent complete excision with negative margins); 12 (52%) developed metastases; and 10 (43%) have died of disease so far, at a median interval of 9 months after diagnosis. Despite the relative rarity of carcinomas in the pediatric population, myoepithelial carcinoma seems to be disproportionately common among children and often has an aggressive clinical course.

Atypical genital nevi. A clinicopathologic analysis of 56 cases

Atypical genital nevi are rare melanocytic lesions that most commonly arise on the vulva of young women. They are currently regarded as nevi of special sites, in that despite histologically worrisome features, their clinical behavior is reportedly benign. However, only few studies with limited follow-up data are available. To better characterize the clinical presentation and behavior of these lesions and to further delineate their histologic features, we retrieved 56 atypical genital nevi arising in the lower female genital tract from our departmental and consultation files. The 56 lesions arose in 55 female patients with a median age of 26 years (range, 6 to 54 y). The dominant histologic feature was a lentiginous and nested junctional component composed of prominent round or fusiform nests, which often showed retraction artifact and/or cellular dyscohesion. Cytologic atypia was mild in 11 cases (20%), moderate in 34 (60%), and severe in 11 (20%). Ten cases (18%) showed focal pagetoid spread, with extension to the granular layer and stratum corneum in 1 case. The atypical junctional melanocytic proliferation was associated with a large common dermal nevus component that dominated the lesion in 26 cases (46%). Adnexal spread (46%) and nuclear atypia of melanocytes situated in the superficial dermis (39%) were relatively common, but dermal mitoses (7%) were uncommon and maturation was present in all cases. A broad zone of dense eosinophilic fibrosis within the superficial dermis was a frequent finding (41%). Clinical follow-up was available in 45 cases (80%) with a median follow-up period of 3.5 years (range, 1 to 16 y). Only 1 lesion recurred, 1.5 years after the initial excision. The original nevus in this patient had only mild cytologic atypia and was present at the margins of excision. The recurrent/persistent nevus was reexcised, and there was no further clinical recurrence in 11.5 additional years of follow-up. Our data support the hypothesis that atypical genital nevi have a benign clinical course despite their occasionally striking cytologic and architectural atypia. Awareness and recognition of this group of melanocytic lesions is important to avoid over diagnosis as melanoma with subsequent wide excision and possibly sentinel lymph node biopsy.

Deep Benign Fibrous Histiocytoma : Clinicopathologic Analysis of 69 Cases of a Rare Tumor Indicating Occasional Metastatic Potential

Benign fibrous histiocytoma (FH) is one of the most common mesenchymal neoplasms of the skin. Several histologic variants of cutaneous FH have been described, some of which also have distinct clinical features including a propensity for local recurrence. Deep benign FH is an uncommon and poorly recognized clinical subtype that arises in subcutaneous or deep soft tissue. Only a single small series of these neoplasms has been published, and their clinical behavior is not well characterized. In this study, we report the clinicopathologic features of 69 deep FH retrieved from our consultation files. The patients included 41 males and 28 females, ranging in age from 6 to 84 years (median, 37 y). The most common anatomic location was the extremities (58%); the remainder arose on the head and neck (22%), trunk (11%), and in the deep soft tissue of the retroperitoneum, mediastinum, or pelvis (9%). All lesions arising in nonvisceral soft tissue were subcutaneous. The tumors ranged from 0.5 to 25 cm in size (median, 3.0 cm) and were well circumscribed grossly and microscopically. All tumors were composed of bland ovoid to spindle cells arranged in a storiform pattern with admixed lymphocytes. Multinucleate giant cells, osteoclastic giant cells, and/or foam cells were present in 59% of cases, whereas the other 41% were cytologically monomorphic, often resembling cellular FH. Other common findings included a hemangiopericytomalike vascular pattern (42%) and stromal hyalinization (39%). Four cases were classified as atypical deep FH due to the presence of scattered markedly pleomorphic spindle cells within an otherwise histologically typical lesion. The median mitotic rate was 3/10 HPF; 10 cases (14%) had >10 mitoses/10 HPF. Necrosis (2 cases) and lymphovascular invasion (1 case) were rare. Immunohistochemistry revealed expression of CD34 in 20/50 cases (40%), smooth muscle actin in 15/40 (38%), and focal desmin in 1/12 (8%). Of the 37 patients for whom clinical follow-up was available (median, 40 mo), 8 (22%) had a local recurrence; in all 8 cases, the tumor had been marginally or incompletely excised. Metastases occurred in 2 patients (5%), both of whom ultimately died of disease; however, this number is likely exaggerated due to consultation bias. The metastasizing tumors were large (6 and 9 cm) and 1 had tumor necrosis but they were otherwise histologically identical to the nonmetastasizing lesions. In summary, deep FH has many histologic features in common with cutaneous cellular FH; however, it usually has a more diffusely storiform pattern than the latter, is well circumscribed, and may have striking hemangiopericytomalike vessels. Similar to the cellular, aneurysmal, and atypical variants of FH, deep FH recurs in approximately 20% of cases and may rarely metastasize.

Utility of p63 in the differential diagnosis of atypical fibroxanthoma and spindle cell squamous cell carcinoma

Atypical fibroxanthoma (AFX), spindle cell squamous cell carcinoma (SCSCC) and spindle cell melanoma are the primary entities in the differential diagnosis of a cytologically atypical spindle cell tumor arising on sun‐damaged skin. AFX is generally regarded as a diagnosis of exclusion in this context: in the absence of S100 or keratin reactivity, a diagnosis of AFX is favored. However, keratin reactivity may be focal or even absent in SCSCC, and although numerous positive markers of AFX have been proposed, none has shown sufficient sensitivity and specificity for routine diagnostic use. We evaluated 20 AFX and 10 SCSCC with a panel of cytokeratins and p63 to assess the utility of the latter antibody in this differential diagnosis. All 10 SCSCC showed strong expression of p63, whereas all 20 AFX were p63 negative. Two additional cases (excluded from the study) were negative for keratins and S100 on initial shave biopsies, resulting in a favored diagnosis of AFX, but p63 stains performed retrospectively were positive. However, review of the excision specimens in both cases revealed deep subcutaneous extension, excluding AFX. p63 reactivity argues against the diagnosis of AFX and is therefore a useful addition to the standard immunohistochemical panel for cutaneous spindle cell neoplasms.

Non-bullous neutrophilic dermatosis : an uncommon dermatologic manifestation in patients with lupus erythematosus

Background:  Rare cases of a non‐bullous neutrophilic dermatosis occurring in patients with lupus erythematosus (LE) have been reported, often as the presenting manifestation of the disease.

Increased diagnosis of thin superficial spreading melanomas: A 20-year study

BACKGROUND Diagnostic practice by dermatopathologists evaluating pigmented lesions may have evolved over time. OBJECTIVES We sought to investigate diagnostic drift among a group of dermatopathologists asked to re-evaluate cases initially diagnosed 20 years ago. METHODS Twenty nine cases of dysplastic nevi with severe atypia and 11 cases of thin radial growth-phase melanoma from 1988 through 1990 were retrieved from the pathology files of the Massachusetts General Hospital. All dermatopathologists who had rendered an original diagnosis for any of the 40 slides and the current faculty in the Massachusetts General Hospital Dermatopathology Unit were invited to evaluate the slide set in 2008 through 2009. RESULTS The mean number of melanoma diagnoses by the 9 study participants was 18, an increase from the original 11 melanoma diagnoses. A majority agreed with the original diagnosis of melanoma in all 11 cases. In contrast, a majority of current raters diagnosed melanoma in 4 of the 29 cases originally reported as dysplastic nevus with severe atypia. Interrater agreement over time was excellent (kappa 0.88) and fair (kappa 0.47) for cases originally diagnosed as melanoma and severely atypical dysplastic nevus, respectively. LIMITATIONS The unbalanced composition of the slide set, lack of access to clinical or demographic information, access to only one diagnostic slide, and imposed dichotomous categorization of tumors were limitations. CONCLUSIONS A selected cohort of dermatopathologists demonstrated a general trend toward the reclassification of prior nonmalignant diagnoses of severely atypical dysplastic nevi as malignant but did not tend to revise prior diagnoses of cutaneous melanoma as benign.

Osteofibrous dysplasia and adamantinoma in children and adolescents: a clinicopathologic reappraisal.

Osteofibrous dysplasia (OFD) and adamantinoma are rare and most commonly arise in the tibia of young individuals. Although OFD has typical histopathologic features, areas resembling OFD have often been noted at the periphery of otherwise classic adamantinomas, and some have suggested that OFD may be either a precursor to or a regressive phase of adamantinoma. The so-called OFD-like adamantinoma encompasses some features of both OFD and adamantinoma. We studied the clinical, imaging, histopathologic, immunohistochemical, ultrastructural, and molecular features of 16 OFD and 8 adamantinomas (5 OFD-like and 3 classic) in an attempt to further define their morphology, clinical course, and relationship. Patients with OFD were generally younger than those with adamantinoma. Osteoblastic and osteoclastic activity was more prominent in OFD than in OFD-like adamantinoma. In addition to the inconspicuous small clusters of epithelial cells in OFD-like adamantinoma, isolated keratin-positive cells with a unique ultrastructural hybrid fibroblastic-epithelial phenotype were found in the stroma of all OFD and OFD-like adamantinomas. Fluorescence in situ hybridization analysis revealed trisomies 7, 8, and/or 12 in the spindle cell stroma of OFD, OFD-like, and classic adamantinoma, supporting a neoplastic origin of OFD and a common histogenesis for all 3 lesions. Trisomies were not observed in osteoblasts or osteoclasts suggesting that the osseous component is reactive and non-neoplastic. Of the 11 OFD patients with follow-up (median, 4.5 y), all 3 who underwent incisional biopsy had persistent, nonprogressive disease and 2 of 8 who underwent curettage or wide excision had recurrence; none developed adamantinoma. All 6 adamantinoma patients with follow-up (3 classic and 3 OFD-like) were treated with wide excision. One with classic adamantinoma died of pulmonary metastases 9 years after presentation; the other 5 were free of disease with a median follow-up of 12 years. None of the classic adamantinomas evolved into OFD-like adamantinoma or OFD. Although the histopathology, immunohistochemistry, ultrastructure, and cytogenetics indicate that these lesions are closely related, our data and the literature suggest that only classic adamantinoma has malignant potential. OFD, OFD-like adamantinoma, and classic adamantinoma appear to show a progressive complexity of cytogenetic aberrations, perhaps indicative of a multistep neoplastic transformation.

Expression patterns of MITF during human cutaneous embryogenesis: evidence for bulge epithelial expression and persistence of dermal melanoblasts

Background:  The mechanisms whereby melanocytes populate the epidermis and developing hair follicles during embryogenesis are incompletely understood. Recent evidence implicates an intermediate mesenchymal stage in this evolutionary process in which HMB‐45‐positive melanocyte precursors (‘melanoblasts’) exist both in intradermal as well as intraepithelial and intrafollicular compartments. The melanocyte master transcriptional regulator, microphthalmia transcription factor (MITF), identifies mature melanocytes as well as melanocyte precursor stem cells that reside in the bulge region of the hair follicle.

Intravascular cytotoxic T-cell lymphoma : A case report and review of the literature

Intravascular lymphoma (IVL) is a rare subtype of extranodal diffuse large B-cell lymphoma in the World Health Organization classification. Although the majority of cases are of B-cell lineage, cases of IVL with a T-cell phenotype and, rarely, histiocytic and natural killer (NK)-cell phenotypes have been reported. We report a case of T-cell IVL with a cytotoxic phenotype. A 62-year-old male presented with erythematous patches and plaques on the lower extremities, and a biopsy revealed IVL with an activated cytotoxic phenotype (CD56(+), perforin+, granzyme B+, TIA-1+, CD3epsilon(+), CD20(-), CD4(-), CD8(-), CD5(-), and T-cell receptor [TCR] betaF1(-)), consistent with either NK-cell or T-cell origin. TCR gene analysis showed a monoclonal T-cell population, supporting the diagnosis of a T-cell IVL. Although the patients skin lesions were refractory to combination chemotherapy and salvage chemotherapy regimens, there has been no evidence of disease progression in 24 months of follow-up.

Expression of MiTF may be helpful in differentiating cellular neurothekeoma from plexiform fibrohistiocytic tumor (histiocytoid predominant) in a partial biopsy specimen.

Background Overlapping histopathologic features of cellular neurothekeoma (CNT) and plexiform fibrohistiocytic tumor (PFHT), when both are predominantly composed of histiocytoid cells, make distinction between these entities challenging. Some have suggested that CNT and PFHT are related entities. No prior study has demonstrated a reliable immunohistochemical panel to differentiate these entities. Methods Skin biopsies diagnosed as CNT and PFHT, from 2004 to 2010 were retrieved with accompanying pathology reports. Each case was reviewed by at least 2 dermatopathologists and 2 soft tissue pathologists for confirmation of diagnosis. All cases were then evaluated for immunohistochemical expression of PAX2, NKIC3, CD10, and microphthalmia transcription factor (MiTF). Results Histopathologically, the histiocytoid areas of each tumor shared similar architecture, demonstrating nests and fascicles of histiocytoid to spindled cells, with some separation of nests by collagen bands. Both CNT and PFHT were uniformly positive for NKIC3 and CD10, and both were frequently PAX2 positive. MiTF was strongly and diffusely positive in CNT and was consistently negative in the PFHT. Conclusions CNT and PFHT share many histopathologic features and immunohistochemical staining patterns. Of the stains we evaluated, we found that expression of MiTF may be a reliable marker for distinguishing CNT from histiocytoid-predominant PFHT, especially in instances where only a small part of the tumor is sampled for evaluation.