Cuticular Poroma: A Rare Poroma Variant Simulating a Malignant Neoplasm That Often Harbors YAP1::NUTM1 Fusions Similar to Their Conventional Counterparts.

ABSTRACT: Cuticular poroma is a rare variant of poroma composed of exclusively or predominantly cuticular cells, namely of large cells with ample eosinophilic cytoplasm. We report 7 cases of this rare tumor identified among 426 neoplasms diagnosed as poroma or porocarcinoma. The patients were 4 males and 3 females, ranging in age from 18 to 88 years. All presented with a solitary asymptomatic nodule. The location included knee (2 cases), shoulder, thigh, shin, lower arm, and neck (each 1). All lesions were surgically removed. No evidence of disease was observed in 5 patients with available follow-up (range 12-124 months).Microscopically, all neoplasms were composed of variably sized, focally closed packed, or interconnecting nodules constituted mostly of cuticular cells. Small poroid cells were a focal feature in 5 tumors, whereas in the remaining 2 cases, poroid cells with conspicuous but still in minority. Five neoplasms were somewhat asymmetric, with irregular outlines. Ductal differentiation and intracytoplasmic vacuoles were seen in 6 tumors. Other features variably encountered were conspicuous intranuclear pseudoinclusions, cystic change, occasional multinucleated cells, increased mitoses, and stromal desmoplasia. Four of the 5 tumors analyzed with next-generation sequencing yielded YAP1::NUTM1 fusions. In addition, various mutations, mostly of unknown significance were identified in one neoplasm.

[Periodontal rehabilitation in a deaf patient with symptomatic epilepsy in Sturge-Weber syndrome - a case report]. / Parodontale Rehabilitation bei einer gehörlosen Patientin mit symptomatischer Epilepsie bei Sturge-Weber-Krabbe-Syndrom. Ein Fallbericht.

When a syndrome forms the background of a systemic involvement of periodontal disease, it is necessary to fully exploit the resources outside, which soon reaches its limits in private practice. In the patient's environment, it must be checked whether support for the patient can be guaranteed. Without support, as in this presented case, the patient's oral hygiene could hardly be maintained. This article reports on a female patient who was referred to the Center for Dental Medicine at the University of Zurich. In addition to various secondary carious lesions, an apical whitening, two carious wisdom teeth and two extremely mobile molars in the third quadrant, the patient had chronic, localized advanced (stage III, grade B) periodontitis associated with systemic disease (deafness and Sturge-Weber syndrome). For two years, the patient was treated at the Department of Periodontology. Due to the strong bleeding tendency on the left side, facial localization of the naevus flammeus, the patient was partially referred to the Polyclinic of Oral Surgery and treated there. Numerous oral hygiene sessions, scaling and root planing, restoration with composite fillings, a root filling, removal of wisdom teeth and finally removal of hypermobile molars 36 and 37 during corona lockdown were performed. In the meantime, the patient has been orally rehabilitated. Home oral hygiene was reorganized with the patient's family and the patient was discharged to a close supportive periodontal recall for the time being.

Actinomycosis as a Rare Local Manifestation of Severe Periodontitis.

Actinomycosis is a chronic suppurative infection primarily caused by anaerobic gram-positive filamentous bacteria, primarily of the genus Actinomyces. Oral-cervicofacial actinomycosis is the localization found most often, presenting as a soft tissue swelling, an abscess, a mass lesion, or sometimes an ulcerative lesion. Periodontitis-like lesions, however, are rare findings. This report describes the case of a 41-year-old healthy female patient (nonsmoker), who was referred to the clinic with dull and throbbing pain in the second quadrant. Tooth 25 showed increased mobility and probing pocket depths up to 10 mm, with profuse bleeding upon probing. Radiographically, considerable interproximal horizontal bone loss was found, and the diagnosis of periodontitis stage 3, grade C was made. The situation was initially stabilized with adhesive splinting and local anti-infective therapy. Two weeks later, the bone defect was treated with guided tissue regeneration (GTR) using a xenogenic filler material (BioOss Collagen) and a resorbable membrane (Bio-Gide). Due to a suspicious appearance of the excised granulation tissue, the collected fragments were sent for histopathological evaluation. This evaluation revealed a chronic granulomatous inflammation with the presence of filamentous bacterial colonies, consistent with Actinomyces. The patient was successfully treated. While there are only few reports in the literature, actinomycotic lesions represent a rare but possible finding in cases with localized periodontal destruction. In conclusion, systematic biopsy of the infrabony tissue in localized periodontal lesions may help to provide a more accurate counting of Actinomyces-associated lesions, thereby improving diagnosis, therapy, and prevention.

Cancer testis antigen expression in testicular germ cell tumorigenesis.

Cancer testis antigens are encoded by germ line-associated genes that are present in normal germ cells of testis and ovary but not in differentiated tissues. Their expression in various human cancer types has been interpreted as 're-expression' or as intratumoral progenitor cell signature. Cancer testis antigen expression patterns have not yet been studied in germ cell tumorigenesis with specific emphasis on intratubular germ cell neoplasia unclassified as a precursor lesion for testicular germ cell tumors. Immunohistochemistry was used to study MAGEA3, MAGEA4, MAGEC1, GAGE1 and CTAG1B expression in 325 primary testicular germ cell tumors, including 94 mixed germ cell tumors. Seminomatous and non-seminomatous components were separately arranged and evaluated on tissue microarrays. Spermatogonia in the normal testis were positive, whereas intratubular germ cell neoplasia unclassified was negative for all five CT antigens. Cancer testis antigen expression was only found in 3% (CTAG1B), 10% (GAGE1, MAGEA4), 33% (MAGEA3) and 40% (MAGEC1) of classic seminoma but not in non-seminomatous testicular germ cell tumors. In contrast, all spermatocytic seminomas were positive for cancer testis antigens. These data are consistent with a different cell origin in spermatocytic seminoma compared with classic seminoma and support a progression model with loss of cancer testis antigens in early tumorigenesis of testicular germ cell tumors and later re-expression in a subset of seminomas.

Phenotype profiling of primary testicular diffuse large B-cell lymphomas.

Primary testicular diffuse large B-cell lymphomas (tDLBCL) are rare neoplasms with few comprehensive studies conducted so far. We aimed to systematically characterize the phenotype of tDLBCL. Forty-five patients from three Swiss hospitals diagnosed with tDLBCL between 1972 and 2009 were reviewed and included in this study. A tissue microarray was assembled, and the protein expression profiles were assessed by immunohistochemistry and fluorescence in situ hybridization for the C-MYC locus. All tDLBCL expressed CD79a, followed by CD20 (98% of cases) and CD19 (93%). One case expressed the germ cell marker OCT4 and showed a rearrangement of C-MYC. Eighty-two per cent of cases showed active STAT signalling by expression of either pSTAT1 or pSTAT3 or both, but not pSTAT5. The p53 was overexpressed in 10% of cases, but p21 staining (∆p21/p53) did not suggest the presence of TP53 mutations. tDLBCL had a median MIB1 labelling index of 40%, and only 6% of cases appeared to have C-MYC rearrangements. Most cases were of the non-germinal centre type (77%), and showed as expected for this cell of origin B-cell lymphoma 2 (BCL2) rearrangements only in 4% and amplifications in 15% of cases, whereas BCL6 was rearranged in 48% of cases. CXCR4 was expressed in 52% of cases, and high CXCR4 expression was of prognostic significance for progression-free survival (p = 0.003). Because 84% of cases expressed nuclear p50, the canonical NF-κB signalling pathway seems to be active. Multimarker phenotyping is important for lineage determination of tDLBCL. Occasionally, tDLBCL can express germ cell markers like OCT4, and they have active STAT signalling mediated through pSTAT1 and pSTAT3 and active canonical NF-κB signalling. tDLBCL are of non-germinal centre/post-germinal centre cell origin and not hyperproliferative. TP53 mutations are unlikely, and C-MYC as well as BCL2 rearrangements are rare, whereas BCL6 is commonly rearranged. CXCR4 might prove to be the first protein-based prognostic marker for tDLBCL, inciting studies in larger cohorts corroborating these findings.

Perineural Invasion in the Absence of Malignancy: Report of Two Cases and Review of the Literature.

Perineural invasion is usually associated with invasion of the perineural space by malignant tumors. In this report, we describe 2 cases of perineural infiltration by benign-appearing epithelial cells in the skin. One case concerns a tumor-free reexcision specimen of a basal cell carcinoma and the other one an ulceration at the outer ear, consistent with acanthoma fissuratum, without a history of a previous excision. This finding was interpreted as a reactive process with dislocation of epithelium from the overlying epidermis into the perineural space.

Expression of histone deacetylases 1, 2 and 3 in histological subtypes of testicular germ cell tumours.

In this study we aimed to evaluate the protein expression of class I histone deacetylases (HDAC) in testicular germ cell tumours (GCT) and to analyse differences between the histological subtypes of testicular GCT. 325 testicular GCT were included in a tissue microarray with each histological subtype of the tumour being separately represented on this array. Expression of class I HDAC isoforms 1, 2 and 3 was assessed by immunohistochemistry. While HDAC2 and 3 were highly expressed in all histological subtypes of GCT, HDAC1 was almost consistently expressed at lower levels. We observed significant differences in the expression of the respective HDACs between seminoma and non-seminoma GCT tissue components. Interestingly, choriocarcinomas showed generally high expression values for all three class I HDAC isoforms. Relevant correlations with clinicopathological parameters could not be demonstrated. Contrasting published findings on other tumour entities, no immediate practical diagnostic or prognostic value for HDAC1-3 in GCT could be inferred. However, the high expression levels might still be indicative for a treatment response to HDAC inhibitors which ought to be evaluated in further studies.

MAGEC2 is a sensitive and novel marker for seminoma: a tissue microarray analysis of 325 testicular germ cell tumors.

Melanoma-associated gene C2 (MAGEC2) is a recently identified cancer testis antigen expressed in normal testicular and placental tissue. It has been detected in some human carcinomas, but its expression in primary testicular germ cell tumors is unknown. Immunohistochemistry was used to study MAGEC2 protein in 325 primary testicular germ cell tumors, including 94 mixed germ cell tumors. Seminomatous and non-seminomatous components were separately arranged and evaluated on tissue microarrays. MAGEC2 expression was compared with POU5F1 (OCT3/4), SOX2, SOX17, KIT and TNFRSF8 (CD30). The mouse monoclonal anti-MAGEC2 antibody (clone LX-CT10.5) revealed a nuclear MAGEC2 expression with little or no background staining. MAGEC2 expression was found in 238 of 254 seminomas (94%), but not in embryonal carcinomas (n=89). POU5F1 (OCT3/4) was positive in 97% of seminomas and all embryonal carcinomas. In contrast, KIT was positive in 94% of seminoma but also in 8% of embryonal carcinomas. TNFRSF8 (CD30) and SOX2 were negative in seminoma and positive in embryonal carcinoma (96 and 90%, respectively). SOX17 was positive in 94% of seminoma and negative in embryonal carcinoma. We conclude that MAGEC2 allows a reliable distinction of seminoma from embryonal carcinomas. Therefore, MAGEC2 represents an additional tool for the differential diagnosis of testicular germ cell tumors.

Merkel cell polyomavirus is present in common warts and carcinoma in situ of the skin.

Polyomaviruses have been linked to diseases of immunosuppressed patients. We sought to determine the prevalence of Merkel cell polyomavirus in benign epithelial skin neoplasms and nonmelanoma skin cancer of immunosuppressed renal transplant recipients and long-term dialysis patients. Merkel cell polyomavirus DNA was detected by polymerase chain reaction (PCR) in 2 (10%) of 20 patients, in carcinomas in situ (Bowen's disease). In one of our patients with Merkel cell polyomavirus-positive carcinoma in situ, 9 (39.1%) of 23 skin lesions at various anatomical locations tested positive for Merkel cell polyomavirus sequences by PCR, including all of his common warts (4/4), half of his carcinoma in situ lesions (3/6), and 2 of his 3 seborrheic keratoses. In a second cohort of immunosuppressed renal transplant recipients, Merkel cell polyomavirus DNA was found in 1 (6.3%) of 16 common warts and in 2 (9.5%) of 21 carcinomas in situ. In immunocompetent individuals, Merkel cell polyomavirus DNA was found in 2 (6.7%) of 30 common warts and in 2 (8.3%) of 24 carcinomas in situ. DNA of other human polyomaviruses was not detected in any of the investigated skin neoplasms. We conclude that common warts and carcinomas in situ can be positive for Merkel cell polyomavirus in immunosuppressed as well as immunocompetent individuals. Remarkably, some of the Merkel cell polyomavirus-positive common warts did not contain human papillomavirus. Furthermore, Merkel cell polyomavirus can be found in various skin neoplasms of the same individual.

Distinct expression patterns of the immunogenic differentiation antigen NY-BR-1 in normal breast, testis and their malignant counterparts.

NY-BR-1 is a differentiation antigen and a potential target for cancer immunotherapy. Its mRNA expression is restricted to breast, testis, prostate and breast cancer by RT-PCR. In this study, we correlated NY-BR-1 protein and mRNA expression on tissue microarrays of mammary, prostatic and testicular malignancies using immunohistochemistry and in situ hybridization with probes for exon 4-7 and 30-33. NY-BR-1 mRNA was confined to primary spermatocytes, suggesting a role in spermatogenesis. Exon 4-7 and 30-33 were equally expressed this cell type. However, NY-BR-1 was absent in all germ cell tumours analyzed (n = 475) and present in one of 56 (2%) prostate carcinomas. In breast, NY-BR-1 mRNA expression was detected in 307 of 442 (70%) primary carcinomas, with strong correlation to its protein expression (p < 0.0001). mRNA expression was significantly stronger and more frequently detected by the exon 30-33 probe than by the exon 4-7 probe (70% vs. 35%, p < 0.0001), indicating the presence of alternative splice variants that lack 5-prime sequences. A similar restricted mRNA pattern was also observed in the normal breast epithelium. NY-BR-1 protein and mRNA correlated significantly with estrogen receptor alpha (ER alpha) protein expression (p < 0.0001), with stronger association to NY-BR-1 mRNA than protein (odds ratio 7.7 compared to 4.6). We identified 4 estrogen response elements (ERE)-like sequences nearby the promoter region, suggesting that NY-BR-1 transcription might be controlled by ER alpha. Accordingly, analysis of matching pairs of primary tumors with their recurrences showed a marked decrease of NY-BR-1 expression in recurrences after tamoxifen treatment (p < 0.0001).

WHO 2004 criteria and CK19 are reliable prognostic markers in pancreatic endocrine tumors.

BACKGROUND: It is difficult to predict the biologic behavior of pancreatic endocrine tumors in absence of metastases or invasion into adjacent organs. The World Health Organization (WHO) has proposed in 2004 size, angioinvasion, mitotic activity, and MIB1 proliferation index as prognostic criteria. Our aim was to test retrospectively the predictive value of these 2004 WHO criteria and of CK19, CD99, COX2, and p27 immunohistochemistry in a large series of patients with long-term follow-up. DESIGN: The histology of 216 pancreatic endocrine tumor specimens was reviewed and the tumors were reclassified according to the 2004 WHO classification. The prognostic value of the WHO classification and the histopathologic criteria necrosis and nodular fibrosis was tested in 113 patients. A tissue microarray was constructed for immunohistochemical staining. The staining results were scored quantitatively for MIB1 and semiquantitatively for CK19, COX2, p27, and CD99. The prognostic value of these markers was tested in 93 patients. RESULTS: The stratification of the patients into 4 risk groups according to the 2004 WHO classification was reliable with regard to both time span to relapse and tumor-specific death. In a multivariate analysis, the CK19 status was shown to be independent of the WHO criteria. By contrast, the prognostic significance of COX2, p27, and CD99 could not be confirmed. CONCLUSIONS: The 2004 WHO classification with 4 risk groups is very reliable for predicting both disease-free survival and the time span until tumor-specific death. CK19 staining is a potential additional prognostic marker independent from the WHO criteria for pancreatic endocrine tumors.

Segmental arterial mediolysis: CTA findings at presentation and follow-up.

OBJECTIVE: Segmental arterial mediolysis is a rare noninflammatory vascular disease of the abdominal splanchnic arteries. The purpose of our study was to retrospectively describe the CT angiography (CTA) findings of this disease and the evolution of those findings over time in five patients. CONCLUSION: Comparison of CTA and digital subtraction angiography suggests that CTA is useful to diagnose symptomatic segmental arterial mediolysis. Midterm CTA follow-up (median, 3 years) indicates that segmental arterial mediolysis lesions may resolve or remain unchanged.

Absence of somatic SDHD mutations in sporadic neuroendocrine tumors and detection of two germline variants in paraganglioma patients.

Allelic loss of the long arm of chromosome 11 is frequent in neuroendocrine tumors (NET) of different organs. However, the MEN1 gene on 11q13 is mutated only in a subset of NET and allelic losses on 11q frequently extend to the telomere. In this genetic region lies the tumor suppressor gene SDHD which is associated with hereditary paragangliomas (PGL1). We sought to determine whether SDHD plays a role in the development of sporadic NET. By mutation and deletion analysis of SDHD we were unable to detect any SDHD mutation in 45 NET of the lung, gastrointestinal tract, pancreas or parathyroid. However, we found allelic deletions in 20 to 50% of all tumors but parathyroid adenomas. Furthermore, we found heterozygous germline variants in 2/8 paragangliomas. A first case of variant c.149 A>G (H50R) was found in a patient with an extra-adrenal pheochromocytoma, the other variant c.34 G>A (G12S) in a patient with a paratracheal paraganglioma, C-cell hyperplasia of the thyroid and hyperplasia of ACTH-producing cells of the pituitary gland. Both variants were absent in 93 controls. Our results demonstrate that somatic SDHD mutations are rare in sporadic NET. However, LOH alone could lead to a complete loss of function since SDHD is an imprinted gene. Furthermore, we describe two germline variants possibly causing hereditary paragangliomas.