Cutaneous epithelioid malignant peripheral nerve sheath tumour: a clinicopathological analysis of 11 cases.

AIMS: Epithelioid malignant peripheral nerve sheath tumour (E-MPNST) is a distinctive variant of malignant peripheral nerve sheath tumour characterized by the predominance of epithelioid cells, diffuse S100 positivity and infrequent association with neurofibromatosis type 1. The aim of this study was to further delineate clinicopathological features of cutaneous E-MPNST, correlate them with disease outcome and discuss differential diagnosis. METHODS AND RESULTS: We analysed 11 cutaneous E-MPNSTs (six males, five females, median age 49 years, median size 1.6 cm). Tumours showed a predilection for lower extremities (45%) and trunk (45%), followed by upper extremity (9%). Follow-up was available for nine of 11 patients (range 24-100 months, median 52 months). Four patients had an uneventful clinical course (44%), two developed local recurrence(s) (22%) and three died due to disseminated disease (33%). No histological parameters were found to predict local recurrence(s), development of distant metastases or disease outcome, including size, percentage of epithelioid component, number of mitoses per 10 high-power fields, degree of nuclear atypia or site of occurrence (dermis, dermis/subcutis, subcutis) (P > 0.05). Immunohistochemically, all tumours were diffusely S100-positive, with a subset displaying loss of integrase interactor 1 (INI1) expression (50%). CONCLUSIONS: Cutaneous E-MPNST has the potential to pursue an aggressive clinical course, associated with wide dissemination and unfavourable disease outcome.

Perineural growth of benign cutaneous sweat gland tumors: a hitherto unrecognized phenomenon unassociated with malignancy.

BACKGROUND: Cutaneous intraneural reactive epithelial proliferations mimicking malignancy include epithelial sheath neuroma, re-excision perineural invasion and reactive neuroepithelial aggregates. Nevertheless, intraneural growth of benign sweat gland tumors has not been reported before. AIMS: To report a predominantly intraneural proliferation of morphologically bland sweat gland tumors, describe their clinicopathological features and correlate them with survival. RESULTS: We analyzed a spiradenoma and a hidradenoma with a prominent intraneural growth, occurring on the back of the 19-year-old woman and on the arm of the 53-year-old woman. Both lesions presented as a painful and slightly raised papule. After complete excision, an uneventful clinical course was observed during the follow-up period of 52 and 54 months. Pathologically, the most striking feature was an almost exclusive intraneural growth within the peripheral nerves of the deep dermis and subcutis. CONCLUSION: We report for the first time the predominantly intraneural growth of benign sweat gland tumors. Although their histogenesis is unknown, perineural displacement due to previous surgery or trauma, as well as development from intraneural embryological epithelial remnants remains possibilities. Long-term follow-up of our patients suggests that intraneural growth of otherwise bland sweat gland tumors does not signify malignancy. Complete excision appears to be sufficient treatment procedure.

Composite lymphoma of mycosis fungoides and cutaneous small B-cell lymphoma in a 73-year-old male patient.

Composite lymphoma of T-cell and B-cell type is uncommon, and the one occurring primarily on skin is extremely rare. Herein, we report a unique case of composite lymphoma of mycosis fungoides and cutaneous small B-cell lymphoma in a 73-year-old male patient. The patient presented with multiple erythematous patches, plaques, and nodules on the upper arms, scalp, and trunk. Four punch biopsies of arm and scalp lesions demonstrated lymphoid infiltrate in superficial to deep dermis with a characteristic zone distribution of T-cell and B-cell components. T cells were distributed in papillary and perifollicular dermis and displayed a larger size with convoluted nuclei, whereas B cells were small sized, assuming nodular infiltrate in mid-deep dermis with coexpression of CD5. Molecular test detected clonal rearrangement of both TCRG and IGH/K genes with identical amplicons for each gene in all 4 biopsies. Clinical staging revealed no extracutaneous lesions. A multidisplinary approach is emphasized to establish a definitive diagnosis.

HPV16 variant lineage, clinical stage, and survival in women with invasive cervical cancer.

BACKGROUND: HPV16 variants are associated with different risks for development of CIN3 and invasive cancer, although all are carcinogenic. The relationship of HPV 16 variants to cancer survival has not been studied. METHODS: 155 HPV16-positive cervical cancers were categorized according to European and non-European variant patterns by DNA sequencing of the E6 open reading frame. Clinico-pathologic parameters and clinical outcome were collected by chart review and death registry data. RESULTS: Of the 155 women (mean age 44.7 years; median follow-up 26.7 months), 85.2% harbored European variants while 14.8% had non-European sequences. HPV16 variants differed by histologic cell type (p = 0.03) and stage (1 vs. 2+; p = 0.03). Overall, 107 women (68.0%) were alive with no evidence of cancer, 42 (27.1%) died from cervical cancer, 2 (1.3%) were alive with cervical cancer, and 4 (2.6%) died of other causes. Death due to cervical cancer was associated with European variant status (p < 0.01). While 31% of women harboring tumors with European variants died from cervical cancer during follow-up, only 1 of 23 (4.4%) non-European cases died of cancer. The better survival for non-European cases was partly mediated by lower stage at diagnosis. CONCLUSIONS: Overall, invasive cervical cancers with non-European variants showed a less aggressive behavior than those with European variants. These findings should be replicated in a population with more non-European cases.

Tissue microarray analysis of ezrin, KBA.62, CD166, nestin, and p-Akt in melanoma versus banal and atypical nevi, and nonmelanocytic lesions.

Multiple melanocytic markers are useful for differentiating between melanoma and nonmelanocytic lesions but generally do not distinguish melanoma from nevi and atypical melanocytic lesions. We sought to determine if several immunohistochemical markers recently described in the literature, including ezrin, KBA.62, p-Akt, CD166, and nestin, may be helpful in distinguishing these lesions. One hundred ten tissue microarray samples were scored for nestin and CD166 and 220 samples for ezrin, KBA.62, and p-Akt. We found that putative stem cell markers nestin and CD166 were both expressed in most melanomas (86% and 65% of samples, respectively), including desmoplastic melanoma, but were also expressed at similar levels in nevi (79% and 74%, respectively). In addition, these markers were not specific for melanocytic lesions. Ezrin was also expressed in both nevi and melanoma (81% each), including desmoplastic melanoma (75%), and in neural tumors. KBA.62 stained more cases of nevi versus melanoma (93% and 65%, respectively) and was positive in 53% of desmoplastic melanoma. However, it was also positive in several nonmelanocytic tumors. P-Akt expression was generally weak but was increased in nevi (75%) versus melanoma (43%), and was lost in desmoplastic melanomas (5%). Overall, only KBA.62 and p-Akt expression differed between melanoma and nevi, and none of these markers were completely specific for melanocytic tumors versus nonmelanocytic lesions.

Comparison of 2 line blot assays for defining HPV genotypes in oral and oropharyngeal squamous cell carcinomas.

Patients with invasive oral and oropharyngeal squamous cell carcinomas infected with human papillomaviruses (HPV) demonstrate improved survival. HPV detection in tumors may assist in risk stratification of patients and in guiding optimum treatment. Two reverse line blot assays [Linear Array (LA) and INNO-LiPA (LiPA)] were evaluated for detection of HPV genotypes in paraffin-embedded biopsies. Overall, 82.4% of 131 biopsies were HPV+ by LiPA versus 61.1% by LA (κ = 0.32). Completely concordant results were observed in 52.7% of cases: 18 negative and 51 with exactly the same genotype(s). An additional 13 cases had partial agreement. These 82 completely or partially concordant cases revealed a high rate of HPV positivity (78.0%), primarily involving HPV16 (90.6%). HPV+ tumors occurred preferentially in the oropharynx, especially tonsils, with trends for male patients and poor differentiation. Significant differences in these associations were found when LA and LiPA results were analyzed independently. No relationships were found between tumor HPV status and tobacco or alcohol use.

Unusual palisading and necrotizing granulomas associated with a lubricating agent used in lipoplasty.

Palisading granulomas with necrobiosis are frequently encountered in dermatopathology, with granuloma annulare, necrobiosis lipoidica diabeticorum, and rheumatoid nodule being the most frequently rendered diagnoses. We report a series of 9 patients who developed palisading, necrobiotic, and necrotizing granulomas, associated with the presence of foreign material introduced through the use of a lubricating agent containing a copolymer (Carbopol 934) for liposuction. The patients ranged in age from 29 to 54 years old and presented with multiple, disfiguring, and nonhealing wounds at sites where lipoplasty had been performed. All specimens showed similar histologic findings, with the formation of palisading granulomas around extensive areas of necrobiosis with foci of true necrosis. Spaces containing minute fragments of crystalloid-appearing foreign material, birefringent with polarized light, were also identified. Special stains including acid fast, Gram, Giemsa, and/or periodic acid-Schiff were negative for organisms in all cases, as were cultures performed in 5 cases. Given the presence of foreign material and true necrosis, these findings were inconsistent with granuloma annulare, necrobiosis lipoidica diabeticorum, or rheumatoid nodule and were interpreted as a unique reaction to the foreign material. Therefore, this seems to be a distinct reaction pattern that has not been previously reported in the literature and may be important to include in the differential diagnosis in patients with necrotizing granulomatous disease.

Association of HPV16 E6 variants with diagnostic severity in cervical cytology samples of 354 women in a US population.

It has been suggested that DNA sequence variants of HPV16 contribute to differences in the behavior of individual cervical lesions. To address this question, we have analyzed the association of HPV16 variants with diagnostic severity in 354 HPV16-positive Oklahoman women. HPV16 variant status was determined by PCR amplification and DNA sequencing of the E6 open reading frame. European sequences were identified in 86% of samples and 14% were non-European. Of the 51 non-European cases, 61% were Asian-American, 23% African and 16% were Native American variants. European prototype and related variants were present in comparable numbers (43% each) but the relative proportion of each differed with diagnostic category. In general, the proportion of European variants and non-European variants increased with diagnostic severity while the European prototype decreased. When adjusted for age and race (white, black or Hispanic), the increased risk for carcinoma/severe dysplasia for non-European variants was statistically significant with an odds ratio of 3.8 (1.3-10.7). However, the analogous comparison for the European variants, although also showing increased association with carcinoma/severe dysplasia, did not reach statistical significance (OR = 1.6 (95% CI 0.7-3.6). Overall, HPV16 European sequences (both prototype and related variants), were predominant in Oklahoman women including those with cancers. This suggests that while there appear to be differences among the HPV16-variant categories in risk for progression to invasive cancer, all variant categories are associated with the development of invasive cancer.