Primary cutaneous amyloidosis of the external ear: a clinicopathological and immunohistochemical study of 17 cases.

Primary cutaneous amyloidosis includes several forms of localized amyloidosis characterized by superficial amyloid deposits occurring at or near the dermal-epidermal junction in the absence of systemic involvement. Primary cutaneous amyloidosis of the auricular concha and external ear represents a rarely described variant. There have been 27 cases reported in the English language literature, and herein we report 17 additional cases. This article demonstrates that the amyloid observed in this context is generally positive for Congo red, crystal violet and thioflavin T. It also expresses cytokeratin 34ßE12 via immunohistochemistry. Our immunohistochemical results and review of the literature suggest that the amyloid in amyloidosis of the external ear is the result of basal keratinocyte degeneration and does not signify deposition from a systemic or generalized process.

Palisaded neutrophilic and granulomatous dermatitis in association with sarcoidosis.

Palisaded and neutrophilic granulomatous dermatitis (PNGD) has been associated with many conditions including rheumatoid arthritis, systemic lupus erythematosus, systemic vasculitis, and other diseases with circulating immune complexes. Lymphoproliferative conditions, bacterial endocarditis, and various drugs can also induce this condition. Many patients also have symmetric polyarthritis with various serological abnormalities. We present a case of a 46-year-old female who presented with painful erythematous annular plaques and nodules on her legs. The lesions started a week prior to visit and increased in number over the course of the week. The patient had an established history of sarcoidosis with past episodes of uveitis and erythema nodosum. The histopathological findings included a diffuse pandermal infiltrate mostly composed of neutrophils, nuclear debris, and strands of deeply eosinophilic degenerated collagen. Vasculitis was not present. No significant increase in dermal mucin was detected. Based on the clinical and pathological findings, the patient was diagnosed with late-stage PNGD. To our knowledge, this is the first case of PNGD described in an adult patient of sarcoidosis.

Exome sequencing found a novel homozygous deletion in ADCK3 gene involved in autosomal recessive spinocerebellar ataxia.

Autosomal recessive cerebellar ataxia is heterogeneous inherited neurodegenerative disorders with more than 70 involved genes. The development of next generation sequencing opens a new window in rapid diagnosis of such heterogeneous condition in medical genetics laboratories. Here, we present ADCK3; del.CD (229-230) mutation in an Iranian consanguineous family with three cerebellar ataxic boys using whole exome sequencing. The mutation was predicted pathogenic and all the affected individuals were homozygous for the variant. Although, the ADCK3 was previously reported as one of the master genes of ARSC, our mutation was novel as has been not previously reported in dbSNP or literature.

Tactile-like corpuscles in gastric mucosa: a case report.

BACKGROUND: The presence of tactile corpuscle-like structures in Schwannomas, Neurofibromas and Neuroid Intradermal Melanocytic Nevi is well-documented. We report a case describing the presence of such structures in the lamina propria of grossly normal gastric mucosa. CASE PRESENTATION: A 30 year-old male underwent esophagogastrectomy for carcinoma. Examination of hematoxylin and eosin stained sections reveal tactile corpuscle-like structures in the mucosa adjacent to the main tumor mass. CONCLUSION: This is a rare phenomenon and a literature search revealed only one paper describing such structures in the benign colonic mucosa of a colectomy done for carcinoma. We did not come across any cases in the literature describing such structures in gastrointestinal specimen resected for reasons other than carcinoma. To our knowledge this would be the first case reporting the existence of tactile corpuscles-like structures in gastric mucosa.

Translocation (16;18)(p13;q21.3) in follicular lymphoma.

We describe a novel t(16;18)(p13;q21.3) in a male patient with follicular lymphoma. This unique chromosomal rearrangement has never been described in patients with follicular lymphoma. The breakpoint of 16p13 has several hematopoietic neoplasm-related genes such as MHC2TA, a master regulatory gene for HLA-D, and BCMA, tumor necrosis factor receptor super-family. The majority of follicular lymphomas have a rearrangement of the BCL2 gene, which is a pathogenetic factor in their development. The diagnostic and prognostic significance of this new translocation is yet to be determined.

Cutaneous carcinosarcoma: further insights into its mutational landscape through massive parallel genome sequencing.

Cutaneous carcinosarcoma (CCS) is an extraordinarily rare neoplasm with a biphasic morphological pattern exhibiting both epithelial and sarcomatoid components. Although its histogenesis and biological aspects remain poorly understood, previous studies have postulated that this tumor may arise from single cancer stem cells which subsequently differentiate into distinct tumor lineages. In this study, we explored a wide array of mutational hot spot regions, through high-depth next-generation sequencing of 47 cancer-associated genes in order to assess the mutational landscape of these tumors and investigate whether the epithelial and mesenchymal components shared the same genetic signatures. Results from this study confirm that despite their striking phenotypic differences, both elements of this infrequent tumor indeed share a common clonal origin. Additionally, CCS appears to embrace a heterogeneous spectrum with specific underlying molecular signatures correlating with the defining epithelial morphotype, with those carcinosarcomas exhibiting a squamous cell carcinoma epithelial component exhibiting diverse point mutations and deletions in the TP53 gene, and those with a basal cell carcinoma morphotype revealing a more complex mutational landscape involving several genes. Also, the fact that our findings involve several targetable gene pathways suggests that the underlying molecular events driving the pathogenesis of CCS may represent future potential targets for personalized therapies.

Epidermotropic metastatic prostate carcinoma presenting as an umbilical nodule-Sister Mary Joseph nodule.

Carcinoma of the prostate accounts for fewer than 1% of all skin metastases. Cutaneous metastases from prostate carcinoma most often involve the penis, the anterior aspect of the thighs, the suprapubic area, and the perineum, but they also have been reported in the scalp, the chest, the back, and even the face. We report an unusual case of metastatic prostate adenocarcinoma that presented as an umbilical nodule (Sister Mary Joseph nodule) and demonstrated significant epidermotropism histologically. A review of the literature has found only one documented case of prostatic carcinoma metastasizing to the umbilicus, and one other documented case of epidermotropic metastatic prostate carcinoma.

Lipofuscin pigment can be used as a prognostic marker in prostatic adenocarcinoma.

Lipofuscin, known as the "wear and tear" pigment, is seen in cells undergoing regressive changes, the seminal vesicles and the ejaculatory ducts. It is also present in prostatic adenocarcinoma. The purpose of this study is to evaluate the prognostic significance of lipofuscin in prostatic adenocarcinoma. Lipofuscin was evaluated in 736 hematoxylin-eosin-stained slides from 60 conventional and whole-mounted consecutive radical prostatectomies from December 1996 to February 2002. The adenocarcinoma cases were divided into lipofuscin-positive group and lipofuscin-negative group. The Gleason score and pathologic stage were compared between the 2 groups. Percentage of cells positive for p53 and MIB-1 was also compared. Lipofuscin pigment was found in 17 (31%) of 60 prostatic adenocarcinomas as random, sparse, fine, yellow-brown intracytoplasmic granules staining positive for cathepsin D and negative for S-100 protein. Using logistic regression to exclude age as a confounding factor, lower Gleason scores and pathologic stages were demonstrated in the lipofuscin-positive group. There was also a significant difference between the 2 groups in tumor volume, degree of capsular invasion, and positive margins. The difference in seminal vesicle invasion and vascular invasion between the 2 groups was not statistically significant. Lipofuscin in prostatic adenocarcinoma correlates with both lower Gleason score and pathologic stage. Lipofuscin probably indicates slow cellular turnover as suggested by the low proliferation rate and p53 expression. The value of lipofuscin in biopsy as a predictor separating aggressive from indolent disease needs further investigation.

Lack of tissue inhibitor of metalloproteinases-3 results in an enhanced inflammatory response in antigen-induced arthritis.

Tissue inhibitor of metalloproteinases-3 (TIMP-3) is known to inhibit matrix metalloproteinases, aggrecanases, and tumor necrosis factor (TNF)-alpha-converting enzyme (TACE, ADAM17). These metalloproteases participate in different aspects of joint destruction in inflammatory arthritis. To determine the relative importance of this inhibitor in joint pathology, wild-type and Timp3-/- mice were immunized with methylated bovine serum albumin followed by arthritis induction by intra-articular injection of the same antigen. Animals were monitored for up to 14 days after challenge, and joint tissues were analyzed by routine and Safranin O staining and for the presence of aggrecan neoepitopes produced by metalloprotease cleavage. Serum TNF-alpha was measured by immunoassay. Compared to wild-type animals, Timp3-/- mice showed a dramatic increase in the initial inflammatory response to intra-articular antigen injection, and serum TNF-alpha levels were greatly elevated in the Timp3-/- animals after immunization. However, these differences in clinical features disappeared by days 7 to 14. No difference in Safranin O staining or aggrecan cleavage site neoepitope abundance was seen. Thus, in inflammatory joint disease TIMP-3 likely dampens the inflammatory response of TNF-alpha by reducing ADAM17 activity.

Anti-cytokeratin 20 staining of Merkel cells helps differentiate basaloid proliferations overlying dermatofibromas from basal cell carcinoma.

BACKGROUND: Basaloid epidermal proliferations (BEP), morphologically resembling basal cell carcinoma (BCC), have been described overlying dermatofibromas. Distinguishing the two is important because of non-aggressiveness of BEP and local aggressiveness of BCC. The aim of this study is to determine whether CK20 antibody staining for Merkel cells can be used as an adjunct method to differentiate BEP from BCC. METHODS: Ten cases of BEP overlying dermatofibromas were selected. Ten cases of BCC were used as control. The two groups were stained with CK20 antibody. Numerical density of CK20 stained Merkel cells in peri-lesional epidermis, BEP and BCC was determined by examining 300 cells at 400X in two separate areas by three independent pathologists. To determine statistical significance, the results were compared using t-test method. RESULTS: Density of Merkel cells in peri-lesional epidermis was 0.2-0.3%. No merkel cells were detected in the BCC. BEP overlying dermatofibromas showed an obvious increase in CK 20 stained Merkel cells. The difference was statistically significant (P < 0.02) CONCLUSIONS: We report a significant increase in CK20 stained Merkel cells in BEP overlying dermatofibromas as compared to BCC. CK20 antibody staining for Merkel cells can be used as an adjunct method to differentiate BEP overlying dermatofibromas from BCC. Mahmoodi M, Asad H, Salim S, Kantor G, Minimo C. Anti-CK20 staining of Merkel cells helps differentiate basaloid proliferations overlying dermatofibromas from basal cell carcinoma.