Clinicopathologic findings in (anti-FcepsilonR1alpha) autoimmune-related chronic urticaria.

BACKGROUND: One cause of chronic urticaria is autoreactivity which is diagnosed by detecting autoantibodies against the IgE receptor alpha subunit (anti-Fc R1alpha). OBJECTIVE: To compare the histopathologic features of chronic urticaria patients testing positive for anti-IgE receptor antibody (Ab) to those testing negative. METHODS: Totally, 438 patients with a clinical presentation of chronic urticaria (2011-2013) had anti-IgE receptor Ab tested and 37 of those patients had skin biopsy. We evaluated microscopic features including: spongiosis, dermal edema, presence of mast cells, density of lymphocytic infiltration, predomination of eosinophils/neutrophils; intravascular neutrophils and presence of vasculitis. The aforementioned features were compared between negative and positive anti-IgE receptor Ab groups. RESULTS: Of 37 patients , 69% were women and 31% were men. 49% had positive anti-IgE receptor Ab and 51% had negative anti-IgE receptor Ab. In the positive anti-IgE receptor Ab group, 83% showed intravascular neutrophils. Eosinophil predominance was identified in 72% and neutrophil predominance was identified in 28%. In the negative anti-IgE receptor Ab group, 89% showed intravascular neutrophils. Eosinophil predominance was identified in 53% and neutrophil predominance was identified in 47%. There was no evidence of vasculitis in either group. CONCLUSION: There were no significant histopathologic differences between the anti-IgE receptor Ab positive and negative cases. Therefore, serum testing for anti-IgE receptor Ab is required to identify this subgroup of chronic urticaria patients.

Cutaneous meningioma: a potential diagnostic pitfall in p63 positive cutaneous neoplasms.

Cutaneous meningiomas are divided into three groups. Type I lesions present at birth and are derived from ectopic arachnoid cells. Type II lesions usually present in adults and are derived from arachnoid cells surrounding nerve bundles. Type III lesions are due to direct extension or metastasis from dural-based neoplasms. Dural-based meningiomas are known to express p63. The aim of our study is to examine the expression of p63 in type II and type III meningioma. Two cases of cutaneous meningioma (type II and type III) were evaluated for the expression of p63, EMA, CK 5/6, S100 and CD31. The cells of interest were spindled to epithelioid and arranged in a whorling pattern. Immunohistochemical staining showed expression of EMA and p63 in both cases, while stains for CK 5/6, S100 and CD31 were negative. Among cutaneous tumors, p63 is considered a marker of epithelial derivation, as it is positive in epidermal and adnexal neoplasms. It is important to be aware of p63 expression in the context of cutaneous meningioma to avoid misinterpretation as an epithelial tumor. On the basis of our small study, it is unlikely that p63 expression would be helpful in distinguishing between type II and type III meningioma, as both may be p63-positive.

Dermal hypersensitivity reaction: a PCR-confirmed pattern of herpetic dermatitis.

BACKGROUND: Herpetic dermatitis due to herpes simplex virus (HSV) and varicella zoster virus (VZV) can present with similar clinical and histopathologic features. Further confounding matters, viral cytopathic changes are not always observed in biopsy specimens. Therefore, use of polymerase chain reaction (PCR) analysis can play an integral role in the definitive diagnosis of herpetic dermatitis and in the distinction of HSV-1/HSV-2 from VZV. METHODS: Forty patients with skin biopsies (2004-2011) had PCR analysis performed to detect HSV-1/2 or VZV. Patient demographics, clinical impression and histopathologic characteristics were reviewed and correlated with PCR findings. RESULTS: Overall, there was complete correlation between clinical impression, histopathology and PCR results in 21 of 40 cases. In 19 cases, clinical impression and histopathology were discrepant and in 15 of these cases PCR confirmed HSV or VZV infection. We also describe 3 cases of herpetic dermatitis without viral change that histopathologically demonstrate the pattern of a dermal hypersensitivity reaction. CONCLUSIONS: The results of this study suggest that routine use of PCR for definitive diagnosis of herpetic dermatitis should be considered when there is a clinical suspicion of herpes virus infection, even when there is a lack of specific histopathologic findings. Additionally, a dermal hypersensitivity reaction should be recognized as one histopathologic manifestation of herpes incognito.

An audit of dermatopathology requisitions: hand written vs. electronic medical record data entry accuracy.

BACKGROUND: At our institution, dermatopathology case requisitions are received in hand written form or via electronic medical record (EMR). Categories for requisition data entry include patient demographics, physician name and procedure site/date. Systematic data entry problems potentially cause considerable documentation error, propagate inaccurate patient information and potentially delay billing/revenue collection. METHOD: We compared dermatopathology data entry errors on hand written requisitions to data entry errors using the EMR. A total of 11,475 requisitions (8545 hand written and 2930 EMR) were included in the study (the time frame was 4/1/2011-9/30/2011). RESULTS: For hand written requisitions, there were 258 data entry errors on 8545 specimens (3.0%). For requisitions entered via EMR, there were 113 errors on 2930 specimens (3.9%). Container labeling, which is a hand written process with both requisition methods, was the most common source of error. CONCLUSIONS: Currently, even with an EMR, containers are at least partially hand labeled and 96% of EMR errors occurred during this process. Other EMR data entry errors are extremely uncommon (4/2930 cases). This suggests introduction of a labeling process entirely linked to EMR data entry could nearly eliminate data entry errors. Although this study focused solely on dermatopathology cases, the findings can be extrapolated to all types of specimens.

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.

Injection site pseudosarcoma in piriformis syndrome.

AIMS: Pseudosarcomatous reactive myofibroblastic proliferations have been described following surgery or trauma at a variety of anatomical sites. These types of reactions have not been previously described at injection sites. Here we evaluated prevalence, morphologic patterns and clinical resolution of such lesions. METHODS AND RESULTS: We analyzed 266 surgical resection specimens obtained during the definitive treatment of piriformis syndrome. Three cases showed exuberant reactive fibroblastic/myofibroblastic intramuscular proliferations, mimicking a sarcoma. In all three cases the surgeries were found to be preceded by local injections of cortisone and bupivacaine. Clinical follow-up revealed no uncontrolled growth. CONCLUSIONS: As the clinical history of injections is often not provided, it is important to be aware of this pitfall when reviewing skeletal muscle resections for entrapment syndromes.

Cystic fibrosis transmembrane conductance regulator is helpful in the distinction of extra-mammary Paget's disease from squamous cell carcinoma in situ (Bowen's disease).

Cystic fibrosis transmembrane conductance regulator (CFTR) represents a cAMP-dependent channel found in normal apocrine glands. The classification and histogenesis of extra-mammary Paget's disease (EMPD) remains controversial, but it is generally accepted that primary EMPD exhibits apocrine differentiation. Therefore, we examined the utility of CFTR in the differential diagnosis of EMPD and squamous cell carcinoma in situ (SCCIS). Twenty-five cases of SCCIS and 14 cases of EMPD were evaluated for immunohistochemical expression of CFTR. Expression was scored as 0 (<5% of cells positive), 1+ (5-75% of cells positive) or 2+ (>75% cells positive). Twenty-three of 25 cases of SCCIS showed no reactivity for CFTR, and the remaining 2 cases showed 1+ staining. Thirteen of 14 cases of EMPD showed 2+ staining, while 1 case showed 1+ staining. We recognize that the pathological appearance along with clinical history and site of occurrence are sufficient to distinguish EMPD and SCCIS in most instances. However, distinction between the two can become more challenging when the location and histopathology are not characteristic. We conclude that when an immunohistochemical panel is diagnostically necessary, the expression of CFTR favors a diagnosis of EMPD over SCCIS.

Cellular neurothekeoma with fascicular growth features mimicking cellular dermatofibroma.

BACKGROUND: Cellular neurothekeoma (CNT) is a benign cutaneous mesenchymal neoplasm. Most demonstrate a lobulated to micronodular architecture. Rarely, CNT demonstrates a predominantly fascicular growth pattern, without prominent sclerosis and thus can mimic cellular dermatofibroma (DF). METHODS: Three CNT with a predominantly fascicular pattern were obtained. The clinicopathologic features and accompanying immunohistochemical stains were evaluated. RESULTS: All cases demonstrated a moderately cellular proliferation of epithelioid to spindle cells with pale to eosinophilic slightly granular cytoplasm, vesicular nuclei, and a single nucleolus arranged in a fascicular pattern with thick collagen bundles at the periphery (collagen trapping). One case had prominent epidermal hyperplasia. The neoplastic cells expressed NKI-C3, CD10, and micropthalmia transcription factor and lacked expression of factor XIIIa, S-100, epithelial membrane antigen, and CD34. CONCLUSIONS: Our cases showed an unusual pattern of CNT with a predominantly fascicular growth pattern, thickened collagen bundles at the periphery, and occasionally epidermal hyperplasia. The overlap with cellular DF is striking. The presence of plump to epithelioid cytomorphology with abundant cytoplasm, with focally prominent nucleoli; the presence of focal lobulated to micronodular growth pattern along with micropthalmia transcription factor positivity; and lack of factor XIIIa expression are helpful in distinguishing fascicular CNT from cellular DFs.

Sarcomatoid renal cell carcinoma presenting in the oropharynx.

Metastasis stemming from a distant malignancy is far less common than an oropharyngeal primary and represents only 1% of all oral neoplasms. The difficulty in diagnosing a metastasis in the oropharynx may be compounded if the lesion is poorly differentiated and bears little resemblance to the primary tumor. We present the case of synchronous metastatic renal cell carcinoma of the mandibular gingiva in a woman with sarcomatoid clear cell renal cell carcinoma. The metastatic lesion was poorly differentiated and lacked expression of the renal cell carcinoma (RCC) antigen. In contrast, PAX-8 staining was strongly positive. This case serves to highlight the diagnostic difficulty posed by poorly differentiated lesions in the oropharynx and reinforces the sensitivity of the cell lineage-specific transcription factor PAX-8 in poorly differentiated RCC.

Extra-acral cutaneous/soft tissue sclerosing perineurioma: an under-recognized entity in the differential of CD34-positive cutaneous neoplasms.

BACKGROUND: Perineuriomas are an uncommon group of tumors composed of perineurial cells of peripheral nerve sheath lineage. Variants include soft tissue (extraneural), intraneural, sclerosing, reticular and plexiform forms. Sclerosing perineuriomas have been reported to occur almost exclusively on the hands of young men. Herein, we report three extra-acral cutaneous/soft tissue perineuriomas that show significant associated sclerosis. METHODS: Skin biopsy specimens from three patients were evaluated for cytomorphology and degree of associated sclerosis, which was classified as either focal or diffuse. Immunohistochemical expression of epithelial membrane antigen (EMA), CD34 and S-100 was also assessed to facilitate further classification. RESULTS: Histopathologically, the tumors showed both focal and diffuse sclerosis, and lesional cells were generally spindled in shape. Immunohistochemical staining showed diffuse positivity for CD34 and focal or diffuse positivity for EMA. The cells uniformly lacked expression of S-100 protein. CONCLUSIONS: Sclerosing perineuriomas can occur in extra-acral locations and should be considered in the differential of EMA-positive cutaneous spindle-cell proliferations. It is also important to recognize that perineuriomas can express CD34 and should be considered in the differential diagnosis of CD34-positive cutaneous neoplasms.

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.

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.

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.

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.

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 patient's 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 patterns of MITF during human cutaneous embryogenesis: evidence for bulge epithelial expression and persistence of dermal melanoblasts.

UNLABELLED: 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. METHODS: To better define the use of MITF expression in the evaluation of melanocyte ontogeny, human embryonic and fetal skin samples (n = 28) at 6-24 weeks gestation were studied immunohistochemically for expression of MITF and Mart-1. Adjacent step sections were evaluated to correlate staining patterns with cell localization in the intraepidermal, intrafollicular and intradermal compartments. RESULTS: At 6-8 weeks, MITF and Mart-1-positive cells were primarily intradermal with only rare positive cells in the epidermis. By 12-13 weeks, most of these cells had migrated into the epidermis, predominantly the suprabasal layers. Between 15-17 weeks, these cells localized to the basal layer and colonized developing hair follicles. Rare intradermal MITF and Mart-1 positive cells were found as late as week 20. At 18-24 weeks, MITF and Mart-1 positive cells were identified in the outer root sheath, bulge, and follicular bulge epithelium, in addition to the epidermis. Unexpectedly, weak but diffuse nuclear MITF expression was also present in the keratinocytes of the bulge area. CONCLUSIONS: The in situ migratory fate of MITF/Mart-1-expressing cells in fetal skin involves a well-defined progression from intradermal to intraepidermal to intrafollicular localization. Occasional intradermal melanocytes may persist after the intraepithelial stages are completed, a finding of potential significance to melanocytic proliferations that may arise de novo within the dermis. Because MITF may play a role in stem cell maintenance, the presence of MITF in bulge epithelial cells suggests that it may be a novel marker for follicular stem cells of both epithelial and melanocytic lineage.

Malignant cutaneous glomus tumor presenting as a rapidly growing leg mass in a pregnant woman.

A 21-year-old pregnant woman presented with a rapidly growing >2 cm nodule on her right leg, involving dermis and subcutaneous tissue. Histologically, the tumor was composed of sheets and nests of neoplastic cells with variable cytomorphology, including typical round to ovoid glomus cells with clear cytoplasm and well-defined cell borders, small cells and spindle cells. Numerous medium to large vessels were present throughout the tumor. Moderate- to high cellularity, nuclear atypia and frequent mitotic figures (42 MF/50 High power field (HPF)) were noted. Immunohistochemistry showed cytoplasmic and membranous expression of actin (HHF-35) and membranous expression of type IV collagen. The histologic features and immunoprofile were consistent with the diagnosis of malignant glomus tumor, a rare soft tissue neoplasm that typically arises on the extremities. Histologic features that infer malignancy in glomus tumors include the combination of large size (>2 cm) and deep location, or atypical mitotic figures, or moderate to severe cytologic atypia with high mitotic activity (>5 mitoses /50 HPF). Although our case was superficially located, the nuclear atypia and mitotic rate, as well as the large size, fulfilled the criteria for a malignant glomus tumor.

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.

Novel karyotypes in giant cell-rich lesions of bone.

Giant cell-rich lesions of bone, including giant cell tumor of bone, giant cell reparative granuloma (GCRG), and aneurysmal bone cyst (ABC), may have overlapping clinical, radiologic, and histopathologic features. In fact, GCRG and solid ABC are currently differentiated solely based on skeletal location. Prior cytogenetic studies have reported that telomeric associations are present in the majority of giant cell tumors of bone, whereas translocations involving 16q22 and/or 17p13 are characteristic of ABCs. There is only one previously published karyotype of a GCRG, which revealed a reciprocal translocation, t(X;4)(q22;q31.3). We report 3 cases of giant cell-rich bone lesions with novel karyotypes: one lesion located in the first metacarpal, a typical location for GCRG, was histologically consistent with a giant cell tumor and showed the following karyotype [46,XX,inv(2)(p13q21),t(inv2;11)(q21;q13)]; the second lesion, also a giant cell tumor of bone, in the sacrum showed the following karyotype [46,XX,r(9)(p24q34)[cp7]/46,idem,?r(16)(p13.3q24)[cp10]/46,XX]. The third lesion, a hard palate mass, had the histopathologic features of a GCRG and a karyotype showing a reciprocal translocation, 46,XY,t(2;10)(q23;q24). These findings suggest that at least a subset of GCRGs may be neoplastic and that these lesions differ cytogenetically from classic giant cell tumors of bone or solid ABC, although the latter entity is otherwise indistinguishable from reparative granuloma. Further cytogenetic characterization of giant cell-rich bone lesions may improve the utility of karyotyping as a tool in their differential diagnosis and may shed light on the pathogenetic relationship between these lesions.