MicroRNAs expression associated with aggressive clinicopathological features and poor prognosis in primary cutaneous melanomas

ola Kala shared this article with you from Inoreader MicroRNAs expression associated with aggressive clinicopathological features and poor prognosis in primary cutaneous melanomas Μέσω Melanoma Research - Current Issue Several studies have focused on identifying microRNAs involved in the pathogenesis of melanoma. However, its association with clinicopathological features has been scarcely addressed. The aim of this study is to identify microRNAs expression profiles related to aggressive clinicopathological and molecular features, and to analyze the association with melanoma survival. A retrospective and observational study was performed in a series of 179 formalin-fixed paraffin embedded primary cutaneous melanomas. First, a screening analysis on a discovery set (n = 22) using miRNA gene chip array (Affymetrix, Santa Cl ara, California, USA) was performed. Differentially expressed microRNAs were detected employing the software Partek Genomic Suite. Validation of four microRNAs was subsequently performed in the entire series (n = 179) by quantitative real time PCR (qRT-PCR). MicroRNAs expression screening analysis identified 101 microRNAs differentially expressed according to Breslow thickness (≤1 mm vs. >1 mm), 79 according to the presence or absence of ulceration, 78 according to mitosis/mm2 ( View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Infusion reaction to nivolumab in a metastatic melanoma patient. Safe switch to another anti-programmed death-1: a case report

ola Kala shared this article with you from Inoreader Infusion reaction to nivolumab in a metastatic melanoma patient. Safe switch to another anti-programmed death-1: a case report Μέσω Melanoma Research - Current Issue Nowadays, anti-programmed death-1 (PD-1) antibodies are the first-line treatment for metastatic malignant melanoma. An infusion reaction is an adverse event that could occur due to monoclonal antibodies administration and requires prompt diagnosis and treatment. In this article, we report on a case of stage IV malignant melanoma treated with nivolumab, in which a severe infusion reaction occurred, manifesting as flushing and hypotension followed by bronchospasm. The switch to pembrolizumab was both a well-tolerated and effective therapeutic alternative. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Antibody-drug conjugates: an evolving approach for melanoma treatment

ola Kala shared this article with you from Inoreader Antibody-drug conjugates: an evolving approach for melanoma treatment Μέσω Melanoma Research - Current Issue Melanoma continues to be an aggressive and deadly form of skin cancer while therapeutic options are continuously developing in an effort to provide long-term solutions for patients. Immunotherapeutic strategies incorporating antibody-drug conjugates (ADCs) have seen varied levels of success across tumor types and represent a promising approach for melanoma. This review will explore the successes of FDA-approved ADCs to date compared to the ongoing efforts of melanoma-targeting ADCs. The challenges and opportunities for future therapeutic development are also examined to distinguish how ADCs may better impact individuals with malignancies such as melanoma. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The existence of butterfly effect and its impact on the dentinal microhardness and crack formation after root canal instrumentation

ola Kala shared this article with you from Inoreader The existence of butterfly effect and its impact on the dentinal microhardness and crack formation after root canal instrumentation Μέσω Odontology Abstract To compare the microhardness and crack formation in root dentine presented with butterfly effect in lower premolars. Sixty mature lower premolars were selected and divided into the control and experimental groups. Teeth in the experimental group were instrumented up to size 30/.04. The roots were cut horizontally into twelve parts of 1-mm-thick cross-section and were numbered accordingly. They were divided into coronal, middle, and apical root sections. Sections were then viewed under a microscope to determine the presence of butterfly effect and subsequently scored. 8 teeth from both control and experimental groups with the highest and lowest score were selected. Crack formation was inspected and classified into four different types of cracks. Microhardness test was performed using a Vickers hardness test. Higher frequency of butterfly effect was found in the apical root section and root dentine with butterfly effect were harder mesiodistally. The middle and api cal root sections with butterfly effect were harder than the coronal section. No significant difference of dentine hardness between the control and experimental groups. Cracks only occurred in the experimental group and presented in buccolingual direction with a higher rate of Type 1 and Type 2 cracks. Prevalence of butterfly effect in lower premolars increased from coronal to apical with increased hardness mesiodistally. More buccolingual cracks were found in radicular dentine with butterfly effect and most of them exhibited Type 1 and Type 2 cracks. Roots of lower premolar with butterfly effect may be susceptible to a higher rate of vertical root fracture in buccolingual direction, especially after root canal treatment. Thus, special attention should be given not to overload instruments during root canal preparation. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Rare DICER1 and Absent FOXL2 Mutations Characterize Ovarian Juvenile Granulosa Cell Tumors

ola Kala shared this article with you from Inoreader Rare DICER1 and Absent FOXL2 Mutations Characterize Ovarian Juvenile Granulosa Cell Tumors Μέσω The American Journal of Surgical Pathology - Current Issue FOXL2 somatic mutation occurs in a high percentage of ovarian adult granulosa cell tumors and DICER1 mutations in a high proportion of Sertoli-Leydig cell tumors. These mutations have only been studied in a limited number of juvenile granulosa cell tumors (JGCTs), and their occurrence and frequency in these neoplasms is controversial. We aimed to determine the frequency of FOXL2 and DICER1 mutations in a large cohort of 50 JGCTs, and to evaluate the prognostic impact of these mutations. A FOXL2 hotspot mutation was found in 2/50 JGCTs. Review of these 2 cases reclassified them as adult granulosa cell tumors. Thus, FOXL2 mutation was abs ent from our large cohort of JGCTs. DICER1 mutations in the RNase IIIb domain were found in 4 cases. After review of the mutated cases, 1 was reclassified as a gynandroblastoma with a prominent JGCT component. Thus, DICER1 mutations were detected in 3/47 (6%) of pathologically confirmed JGCTs. Our results show that FOXL2 mutations are not present in JGCT, whereas a small percentage of these neoplasms exhibit DICER1 mutations. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Myoepithelioma-like Hyalinizing Epithelioid Tumor of the Foot Harboring an OGT-FOXO1 Fusion

ola Kala shared this article with you from Inoreader Myoepithelioma-like Hyalinizing Epithelioid Tumor of the Foot Harboring an OGT-FOXO1 Fusion Μέσω The American Journal of Surgical Pathology - Current Issue No abstract available View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Gross Specimen Handling Procedures Do Not Impact the Occurrence of Spread Through Air Spaces (STAS) in Lung Cancer

ola Kala shared this article with you from Inoreader Gross Specimen Handling Procedures Do Not Impact the Occurrence of Spread Through Air Spaces (STAS) in Lung Cancer Μέσω The American Journal of Surgical Pathology - Current Issue Spread Through Air Spaces (STAS) is a form of invasion characterized by neoplastic cell dissemination in the lung parenchyma surrounding the outer edge of the tumor. Its possible artifactual origin is widely debated in the literature. The aim of this study is to investigate the potential impact of gross sampling procedures in causing STAS. A prospective series of 51 surgical lung specimens was collected (35 adenocarcinomas, 68.6%; 13 squamous cell carcinomas, 25.5%; 2 large-cell neuroendocrine carcinomas, 3.9%; 1 atypical carcinoid, 2%). The fresh tissue was sectioned with a new and clean blade for each cut, to obtain a tissue slice comprising the upper lung parenchyma, the tumor, and the lower parenchyma. This slice was cut in half and separately processed. The same procedure was repeated in the residual (specular) specimen after formalin fixation. STAS was identified in 33/51 (64.7%) cases, the predominant pattern being cluster formation (29 cases, 87.9%), the remaining 4 cases having single-cell invasion. Comparing STAS detection in upper and lower lung parenchyma areas (ie, before and after the blade crossed the tumor), no significant preferential STAS distribution was observed, indeed being almost overlapping (60.6% and 63.6% for fresh and 61.3% and 65.6% for fixed tissues, respectively). There was no difference between STAS occurrence in freshly cut and fixed corresponding samples. These findings indicate that STAS is not a pathologist-related artifactual event because of knife transportation of tumor cells during gross specimen handling and support the notion that it is a phenomenon preexisting to surgical tissue processing. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Expanding the Spectrum of Microscopic and Cytogenetic Findings Associated With Spitz Tumors With 11p Gains

ola Kala shared this article with you from Inoreader Expanding the Spectrum of Microscopic and Cytogenetic Findings Associated With Spitz Tumors With 11p Gains Μέσω The American Journal of Surgical Pathology - Current Issue A subset of Spitz tumors is associated with a copy number increase of chromosome 11p and activating mutations of HRAS. These aberrations have been reported to occur in association with desmoplastic Spitz nevi. Little is known to what extent 11p gains can also be found in nondesmoplastic tumors. To learn more about the spectrum of microscopic and cytogenetic changes that can be seen in Spitz lesions in association with 11p gains, we reviewed the clinical and pathologic features of 40 cases. Patient ages ranged from 3 to 75 years. The most common anatomic site was the head and neck region, followed by the upper extremities. Prominent d esmoplasia was present in 10 cases. Seven tumors lacked significant stromal fibrosis. Twenty tumors were mitotically active. Novel microscopic features encountered in a few cases include a tumor with a polypoid silhouette and papillomatous surface and rare atypical tumors with a deep bulbous growth pattern. Among 36 cases analyzed by single-nucleotide polymorphism array or comparative genomic hybridization, 28 tumors had gains of the entire or near-entire p-arm of chromosome 11 with no other coexisting unbalanced genomic aberration. Eight cases had additional changes; 6 of these with 1 additional aberration per case, and 2 cases had several chromosomal aberrations. We also examined a subset of tumors by fluorescence in situ hybridization for the HRAS gene locus (11p15.5). All tumors were fluorescence in situ hybridization–positive. In conclusion, we expand the spectrum of pathologic findings associated with Spitz tumors with 11p gains. This cytogenetic aberration is not restricted to desmoplastic Spitz nevi. It can also be seen in nondesmoplastic and papillomatous lesions and atypical melanocytic tumors with a deep bulbous growth. We also document that in some Spitz tumors additional cytogenetic aberrations may be found, the significance of which remains to be determined. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clinicopathologic Features of Varicella Zoster Virus Infection of the Upper Gastrointestinal Tract

ola Kala shared this article with you from Inoreader Clinicopathologic Features of Varicella Zoster Virus Infection of the Upper Gastrointestinal Tract Μέσω The American Journal of Surgical Pathology - Current Issue Reactivation of latent varicella zoster virus (VZV) may be limited to a dermatome or involve multiple organs, including the gastrointestinal tract. Although gastrointestinal manifestations of disseminated zoster have been likened to those of herpes simplex virus (HSV), histologic features of VZV-related injury to the tubular gut are not well-documented. We performed this study to describe the clinicopathologic features of VZV-related gastrointestinal injury. We identified 6 such patients with VZV infection. All involved the upper gastrointestinal tract, affecting the esophagus (n=3), stomach (n=2), or both (n=1). All patients wer e immunocompromised adults with hematologic malignancies (n=5) or a heart transplant (n=1); 3 with hematologic malignancies had received stem cell transplants. Five patients had cutaneous and gastrointestinal zoster; 1 had gastrointestinal disease alone. When compared with 14 HSV-related esophagitis controls, there were several notable differences. VZV caused hemorrhagic ulcers with nodularity or erythema, whereas HSV produced round, shallow ulcers on a background of nearly normal mucosa (P=0.01). VZV-related ulcers featured fibrin-rich, pauci-inflammatory exudates compared with the macrophage-rich exudates of HSV (P=0.003). The cytopathic changes of VZV were present at all levels of the squamous epithelium, especially in a peripapillary distribution. In contrast, HSV inclusions were located in the superficial layers (P=0.003) and detached keratinocytes. Unlike HSV, VZV involved the stomach, producing hemorrhage accompanied by striking apoptosis in the deep glands. We conclude that VZV produces unique patterns of gastrointestinal injury that facilitate its diagnosis. Recognition of gastrointestinal VZV infection is important because it heralds potentially life-threatening disseminated disease. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Pseudocarcinomatous Squamous Hyperplasia Involving Bone: A Diagnostic Pitfall Mimicking Squamous Cell Carcinoma

ola Kala shared this article with you from Inoreader Pseudocarcinomatous Squamous Hyperplasia Involving Bone: A Diagnostic Pitfall Mimicking Squamous Cell Carcinoma Μέσω The American Journal of Surgical Pathology - Current Issue Background: Pseudocarcinomatous squamous hyperplasia (PSH) within the bone is uncommon and closely mimics well-differentiated squamous cell carcinoma (SCC). It arises from cutaneous or mucosal surfaces and grows directly into the bone. This study analyzes a large series of PSH and discusses the clinicopathologic features that facilitate its distinction from SCC. Design: Cases were identified from the surgical pathology files between 1985 and 2020. Results: The 31 cases included 21 males, 9 females, 1 unknown sex; who were 20 to 87 years old (average: 59 y). Sites included mandible—17, maxilla—5, toes—4, and 1 case from finger, femur, tibia, ischium, and unknown. Fourteen patients had a history of SCC, 13 treated with resection and chemoradiation and developed infected osteoradionecrosis, 4—medication-related osteonecrosis, 3—peripheral vascular disease, and diabetes mellitus, 3—trauma, 3—osteomyelitis, 3—unknown, and 1—hematologic malignancy. All cases exhibited severe osteomyelitis and nests of reactive keratinizing squamous epithelium that matured towards the bone surface, lacked significant atypia, or mitotic activity but permeated the medullary cavity. Patients with previous SCC developed PSH after 2 months to 8 years (average: 4 y). Nineteen of 30 patients had follow-up (2 to 48 mo, average: 17 mo); 6 patients experienced repeated debridements over 2 months to 1 year; no patient developed SCC. Conclusions: PSH involving bone is infrequent, complicates severe osteomyelitis, and is often therapy related. The clinical findings are usually not concerning for malignancy, however, the histologic findings are an important diagnostic pitfall because they mimic SCC. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Amyloid-like Fibronectin Deposits in the Liver: A Novel Morphologic Finding

ola Kala shared this article with you from Inoreader Amyloid-like Fibronectin Deposits in the Liver: A Novel Morphologic Finding Μέσω The American Journal of Surgical Pathology - Current Issue Amyloid deposits in the liver are recognized by their hematoxylin and eosin (H&E) findings, consisting of acellular eosinophilic deposits in various compartments of the liver parenchyma, including the stroma, vessels, and rarely the hepatocytes. H&E findings that suggest amyloid are then confirmed by Congo red stains and subtyped when clinically needed. Two cases are reported with sinusoidal deposits of acellular material that closely mimicked amyloid on H&E, but were Congo red negative. Mass spectrometry–based proteomic analysis identified the material as fibronectin. In 1 case, the deposits were located in the sinusoids of a well-differentiated hepatocellular carcinoma and in 1 case in the sinusoids of a benign liver. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Dedifferentiated and Undifferentiated Melanomas

ola Kala shared this article with you from Inoreader Dedifferentiated and Undifferentiated Melanomas: Report of 35 New Cases With Literature Review and Proposal of Diagnostic Criteria Μέσω The American Journal of Surgical Pathology - Current Issue Dedifferentiated melanoma (DM) and undifferentiated melanoma (UM) is defined as a primary or metastatic melanoma showing transition between conventional and undifferentiated components (DM) or lacking histologic and immunophenotypic features of melanoma altogether (UM). The latter is impossible to verify as melanoma by conventional diagnostic tools alone. We herein describe our experience with 35 unpublished cases to expand on their morphologic, phenotypic, and genotypic spectrum, along with a review of 50 previously reported cases (total: 85) to establish the diagnostic criteria. By definition, the dedifferentiated/undifferen tiated component lacked expression of 5 routinely used melanoma markers (S100, SOX10, Melan-A, HMB45, Pan-melanoma). Initial diagnoses (known in 66 cases) were undifferentiated/unclassified pleomorphic sarcoma (n=30), unclassified epithelioid malignancy (n=7), pleomorphic rhabdomyosarcoma (n=5), other specific sarcoma types (n=6), poorly differentiated carcinoma (n=2), collision tumor (n=2), atypical fibroxanthoma (n=2), and reactive osteochondromatous lesion (n=1). In only 11 cases (16.6%) was a diagnosis of melanoma considered. Three main categories were identified: The largest group (n=56) comprised patients with a history of verified previous melanoma who presented with metastatic DM or UM. Axillary or inguinal lymph nodes, soft tissue, bone, and lung were mainly affected. A melanoma-compatible mutation was detected in 35 of 48 (73%) evaluable cases: BRAF (n=20; 40.8%), and NRAS (n=15; 30.6%). The second group (n=15) had clinicopathologic features similar to group 1, but a melan oma history was lacking. Axillary lymph nodes (n=6) was the major site in this group followed by the lung, soft tissue, and multiple site involvement. For this group, NRAS mutation was much more frequent (n=9; 60%) than BRAF (n=3; 20%) and NF1 (n=1; 6.6%). The third category (n=14) comprised primary DM (12) or UM (2). A melanoma-compatible mutation was detected in only 7 cases: BRAF (n=2), NF1 (n=2), NRAS (n=2), and KIT exon 11 (n=1). This extended follow-up study highlights the high phenotypic plasticity of DM/UM and indicates significant underrecognition of this aggressive disease among general surgical pathologists. The major clues to the diagnosis of DM and UM are: (1) presence of minimal differentiated clone in DM, (2) earlier history of melanoma, (3) undifferentiated histology that does not fit any defined entity, (4) locations at sites that are unusual for undifferentiated/unclassified pleomorphic sarcoma (axilla, inguinal, neck, digestive system, etc.), (5) unusual multifoca l disease typical of melanoma spread, (6) detection of a melanoma-compatible gene mutation, and (7) absence of another genuine primary (eg, anaplastic carcinoma) in other organs. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.