Development of a Scoring Rubric Assessing Medical Students' Explanations of Pathology Reports.

CONTEXT.­: With increasing availability of immediate patient access to pathology reports, it is imperative that all physicians be equipped to discuss pathology reports with their patients. No validated measures exist to assess how pathology report findings are communicated during patient encounters. OBJECTIVE.­: To pilot a scoring rubric evaluating medical students' communication of pathology reports to standardized patients. DESIGN.­: The rubric was iteratively developed using the Pathology Competencies for Medical Education and Accreditation Council for Graduate Medical Education pathology residency milestones. After a brief training, third- and fourth-year medical students completed 2 standardized patient encounters, presenting simulated benign and malignant pathology reports. Encounters were video recorded and scored by 2 pathologists to calculate overall and item-specific interrater reliability. RESULTS.­: All students recognized the need for pathology report teaching, which was lacking in their medical curriculum. Interrater agreement was high for malignant report scores (intraclass correlation coefficient, 0.65) but negligible for benign reports (intraclass correlation coefficient, 0). On malignant reports, most items demonstrated good interrater agreement, except for discussing the block (cassette) summary, explaining the purpose of the pathology report, and acknowledging uncertainty. Participating students (N = 9) felt the training was valuable given their limited prior exposure to pathology reports. CONCLUSIONS.­: This pilot study demonstrates the feasibility of using a structured rubric to assess the communication of pathology reports to patients. Our findings also provide a scalable example of training on pathology report communication, which can be incorporated in the undergraduate medical curriculum to equip more physicians to facilitate patients' understanding of their pathology reports.

MAP2K1-mutated melanocytic tumors have reproducible histopathologic features and share similarities with melanocytic tumors with BRAF V600E mutations.

BACKGROUND: Melanocytic tumors driven by MAP2K1 in-frame deletions are among the most recently described class of melanocytic neoplasms. The reported range of diagnoses and associated genomic aberrations in these neoplasms is wide and includes melanomas, deep penetrating melanocytomas, and pigmented epithelioid melanocytoma. However, little is known about the characteristics of these tumors, especially in the absence of well-known second molecular "hits." Moreover, despite their frequent spitzoid cytomorphology, their potential categorization among the Spitz tumors is debatable. MATERIALS AND METHODS: We conducted a retrospective search through our molecular archives to identify sequenced melanocytic tumors with MAP2K1 in-frame deletions. We reviewed the clinical and histomorphological features of these tumors and compared them to similar neoplasms reported to date. In addition, we performed single-nucleotide polymorphism (SNP) array testing to identify structural chromosomal aberrations. RESULTS: Of 27 sequenced tumors, 6 (22%) showed a pathogenic MAP2K1 in-frame deletion (with or without insertion) and were included in this series. Five (83%) were females with lesions involving the upper limb. Histopathologically, all neoplasms were compounded with plaque-like or wedge-shaped silhouettes, spitzoid cytomorphology, and impaired cytologic maturation. All cases showed background actinic damage with sclerotic stroma replacing solar elastosis, variable pagetoid scatter, and occasional dermal mitotic figures (range 1-2/mm2 ). Five cases (83%) had a small component of nevic-looking melanocytes. Biologically, these tumors likely fall within the spectrum of unusual nevi. Five cases (83%) had a relatively high mutational burden and four (67%) showed an ultraviolet radiation signature. Four cases (67%) showed in-frame deletion involving the p.I103_K104del locus while two cases (33%) showed in-frame deletion involving the p.Q58_E62del locus. SNP array testing showed structural abnormalities ranging from 1 to 5 per case. Five of these cases showed a gain of chromosome 15 spanning the MAP2K1 gene locus. DISCUSSION AND CONCLUSION: Melanocytic tumors with MAP2K1 in-frame deletion could represent another spectrum of melanocytic tumors with close genotypic-phenotypic correlation. They are largely characterized by a spectrum that encompasses desmoplastic Spitz nevus as shown in our series and Spitz and Clark nevus as shown by others. Evolutionary, they share many similarities with tumors with BRAF V600E mutations, suggesting they are better classified along the conventional pathway rather than the Spitz pathway despite the frequent spitzoid morphology.

Utility of sequencing for ATP6AP1 and ATP6AP2 to distinguish between atypical granular cell tumor with junctional component and melanoma.

BACKGROUND: Granular cell tumor (GCT) is a S100+ neoplasm with atypical and malignant variants. Similar to melanocytic neoplasms, the tumors make nests and can have junctional components raising a differential diagnosis of melanoma. Nevi and melanomas may also have granular cell cytoplasm. MelanA is useful in distinguishing melanocytic from granular cell lineage, but increasingly MelanA/SOX10 negative melanomas have been recognized by correlation with molecular methods. METHODS: We encountered several cases with morphologic overlap between melanoma and atypical GCT necessitating additional molecular workup. We sequenced two cases and searched our archive for similar cases of GCT with overlapping features of melanocytic lineage. RESULTS: In our two index cases, we excluded melanoma driver mutations and identified frameshift or premature stop codons in ATP6AP1/2 pathognomonic of granular cell lineage. Data retrieved from Cosmic identified 24 melanomas with missense single nucleotide variants (SNVs) in ATP6AP1 but no frameshift or premature stop codons. Twenty-one melanomas had missense SNVs in ATP6AP2. One melanoma had a premature stop codon in ATP6AP2, but this lesion also had a melanoma-associated driver mutation NRASQ61K. We found 1 of 23 additional cases of GCT in our archives with a junctional component and no additional cases with maturation. CONCLUSIONS: Atypical and malignant GCT can have histopathologic overlap with melanoma. Frameshift and premature stop codons in ATP6AP1/2 are specific for granular cell lineage, and capable of excluding melanoma, in the absence of known melanoma-associated driver mutations.

Primary mucoepidermoid carcinoma of the external auditory canal with a CRTC1::MAML2 fusion: A case report and a review of literature.

Mucoepidermoid carcinoma is a malignant neoplasm of exocrine glands that arises predominantly in salivary glands. It is seldom encountered as a primary cutaneous neoplasm, and in those patients, it often involves the external auditory canal. Given their rarity, they can pose a diagnostic challenge and prompt extensive workup. In salivary glands, mucoepidermoid carcinomas commonly harbor CRTC1/3::MAML2 fusions; however, genetic alterations of primary cutaneous neoplasms are less characterized, with previous studies reporting CRTC1 rearrangements in the absence of MAML2 aberrations. Herein, we report a case of a primary cutaneous mucoepidermoid carcinoma of the external auditory canal with a CRTC1::MAML2 rearrangement. We also review the clinical, morphologic, and molecular features of this neoplasm and compare them to those reported in the literature and to histopathologic mimics.

Lymphedematous Fibroepithelial Polyp Without Associated Condom Catheter Use: A Case Report With Review of the Literature.

ABSTRACT: Lymphedematous fibroepithelial polyps are rare proliferations involving the glans penis typically associated with chronic condom catheter usage. To the best of our knowledge, less than 20 cases have been reported in the literature with relatively similar clinical presentation. Herein, we report a case of lymphedematous fibroepithelial polyp not associated with condom usage in a 74-year-old man treated with surgical excision. On histopathological examination, the lesion displayed a hypocellular proliferation of spindled and stellate fibroblasts with intermixed Touton-like giant cells embedded within an edematous stroma with thickened vasculature. Immunohistochemical profiling exhibits strong immunoreactivity for smooth muscle actin, weak positivity for factor XIIIa, and no reactivity for CD34 or desmin. We also conducted a review of the reported range of clinical and histopathological features of this entity in addition to the various hypotheses regarding its pathogenesis. We hope to increase awareness and accurate diagnosis of this entity, which could affect clinical management.

An NTRK-1-associated soft tissue tumor showing distinctive nodules with peripheral accentuation of cellularity.

Lipofibromatosis-like neural tumor is a recently described entity defined by a low-cellularity spindle cell infiltrate in the subcutaneous fat with admixed inflammatory cells. This tumor is histopathologically similar to lipofibromatosis, but unlike lipofibromatosis shows reactivity for S100 and has an NTRK-1 kinase fusion. These lesions are locally aggressive but appear to have a negligible metastatic potential. Subsequently, a more cellular variant has been described with generally low mitotic rate. This variant also displays S100 reactivity and kinase fusions (typically involving NTRK-1), but it has a low risk of metastasis. In this report, we describe a case that aligns with the more cellular variant of NTRK-1 kinase fusion tumors on histopathologic, immunohistochemical, and molecular grounds, but in addition has distinctive nodules with peripheral accentuation of cellularity, reminiscent of those present in epithelioid malignant peripheral nerve sheath tumors. This latter feature is previously undescribed in NTRK kinase fusion soft tissue tumors and offers further support for the presumed neural differentiation of this neoplasm.

Damage characterization of embedded defects in composites using a hybrid thermography, computational, and artificial neural networks approach.

This work presents a hybrid thermography, computational, and Artificial Neural Networks (ANN) approach to characterize beneath the surface defects in composites. Computational simulations are created to model thermography experiments carried out on composite plates with controlled damage in the form of drilled holes. The computational models are then extended to create hypothetical composite component geometries of plates and pipes with embedded defects of varying sizes and shapes. The data from the computational simulations are fed to artificial neural networks to train them to predict and characterize defect sizes and shapes. The predictions from the neural networks are compared to the actual dimensions from the computational models. These predictions show a high level of accuracy especially when quantifying thermal image information and using it to train the neural network. This accuracy is around 10% and 19% for predicting defect depth in plates and pipes, respectively. This hybrid approach has the advantage of not relying on experimental data (experiments were used only for validation) and predicting damage shape and size. This suggests that the methodology used in this study combining lock-in thermography experiments, computational simulations, and ANNs is a viable method for a potential nondestructive testing (NDT) method for detecting embedded defects within composite pipes in real applications. What makes this approach attractive is that it can be used with live thermal images that can be fed directly into the ANN model.

A Rare Case of Myxochondroid Metaplasia of the Plantar Foot With Review of Histopathological Mimics.

ABSTRACT: Chondromyxoid metaplasia can rarely lead to the formation of a distinctive tumor-like proliferation in the plantar foot. This is thought to represent a reactive or reparative process, possibly due to chronic trauma. For the unwary dermatopathologist, this could represent a diagnostic challenge. Herein, we review the clinical, histopathological, and molecular presentation of an athletic 17-year-old boy with a soft tissue mass arising in the right plantar foot. Microscopic examination showed a relatively circumscribed proliferation of spindle cells with abundant chondromyxoid stroma, hyalinization, and diffuse ERG reactivity. We also review characteristics of this entity that help differentiate it from clinical and histopathologic mimics and postulate possible links with soft tissue chondromas and immature chondroid choristoma.

Fatal melanoma with a novel MYO5A-BRAF fusion and small associated conventional nevus: A case report and review of literature.

Kinase fusions play an important role in the pathogenesis of Spitz neoplasms and occasionally non-Spitz neoplasms. We report a case of a 19-year-old woman with a growing nodule on the scalp, morphologically consistent with a diagnosis of melanoma with epithelioid features arising in association with small nevus. This tumor aggressively metastasized and failed to respond to immunotherapy. Next-generation sequencing of a metastatic focus revealed an MYO5A-BRAF kinase fusion with a low mutational burden and fluorescence in situ hybridization (FISH) of the primary melanoma showed similar results. FISH testing of the associated nevus failed because of technical reasons. MYO5A has rarely been reported as the fusion partner with BRAF-rearranged melanocytic tumors. Moreover, this case raises speculations and contributes to the growing literature on the pathogenesis, nomenclature, and tumorigenic pathways in kinase-fusion melanomas. The patient succumbed to disease, which is in concordance with some literature suggesting aggressive behavior of BRAF fusion melanomas with TERT promoter mutations.

Unique orbital biphenotypic tumour with neuroendocrine and sebaceous carcinoma features.

A 60-year-old female presented with a large, left upper eyelid mass that had rapidly expanded in the 3 months prior to presentation. She had a presumed chalazion excised from the same area 1.5 years ago, but no pathology was investigated. On examination, she had a palpebral mass measuring 4.5 cm x 3.5 cm that abutted the globe with extensive conjunctival involvement. Neuroimaging demonstrated lesions concerning for parotid gland metastases. An incisional biopsy demonstrated synaptophysin-positive small blue cells concerning for neuroendocrine carcinoma. The patient underwent orbital exenteration with parotidectomy and radical neck dissection. The excised mass was found to have distinct neuroendocrine carcinoma cells intermingled with sebaceous carcinoma cells, a combination not previously reported.

Predicting melanoma survival and metastasis with interpretable histopathological features and machine learning models.

Introduction: Melanoma is the fifth most common cancer in US, and the incidence is increasing 1.4% annually. The overall survival rate for early-stage disease is 99.4%. However, melanoma can recur years later (in the same region of the body or as distant metastasis), and results in a dramatically lower survival rate. Currently there is no reliable method to predict tumor recurrence and metastasis on early primary tumor histological images. Methods: To identify rapid, accurate, and cost-effective predictors of metastasis and survival, in this work, we applied various interpretable machine learning approaches to analyze melanoma histopathological H&E images. The result is a set of image features that can help clinicians identify high-risk-of-metastasis patients for increased clinical follow-up and precision treatment. We use simple models (i.e., logarithmic classification and KNN) and "human-interpretable" measures of cell morphology and tissue architecture (e.g., cell size, staining intensity, and cell density) to predict the melanoma survival on public and local Stage I-III cohorts as well as the metastasis risk on a local cohort. Results: We use penalized survival regression to limit features available to downstream classifiers and investigate the utility of convolutional neural networks in isolating tumor regions to focus morphology extraction on only the tumor region. This approach allows us to predict survival and metastasis with a maximum F1 score of 0.72 and 0.73, respectively, and to visualize several high-risk cell morphologies. Discussion: This lays the foundation for future work, which will focus on using our interpretable pipeline to predict metastasis in Stage I & II melanoma.

The Incidence of Endoscopic Retrograde Cholangiopancreatography-Related Complications in Patients With Liver Transplant: A Meta-Analysis and Systematic Review.

BACKGROUND: Existing literature on post-endoscopic retrograde cholangiopancreatography (ERCP) complications in patients with liver transplant remains scarce and largely inconsistent. We therefore aimed to systematically review and analyze the literature on complication rates associated with ERCP in patients with liver transplant. METHODS: We performed a comprehensive literature search in PubMed, PubMed Central, Embase, and ScienceDirect databases from inception through March 2020 to identify all the studies that evaluated post-ERCP complications in patients with liver transplant. Effect estimates from the individual studies were extracted and combined using the random effect, generic inverse variance method of DerSimonian and Laird, and a pooled odds ratio (OR) and event rates were calculated. Forest plots were generated, and publication bias was assessed for using conventional techniques. RESULTS: Fourteen studies with a total of 1,787 patients were analyzed. In total, 3,192 ERCPs were performed on these patients. The pooled all-complication rate was 5.2% (95% confidence interval (CI): 0.035 - 0.075). Procedural complications analyzed included post-ERCP pancreatitis 3.4% (95% CI: 0.025 - 0.047), bleeding 1.1% (95% CI: 0.006 - 0.020), infections 0.2% (95% CI: 0.025 - 0.047), and cholangitis 0.8% (95% CI: 0.004 - 0.020). No cases of periprocedural death were reported. The pooled OR for post-ERCP pancreatitis in patients with liver transplant compared to patients without liver transplant was 1.289 (95% CI: 0.455 - 3.653, P = 0.633, I2 = 72.88%). CONCLUSION: Post-ERCP complication rates in liver transplant patients are comparable to the general population and hence, peri-procedural evaluation and management may follow the current standards of care in this patient population.

Diagnosis of melanoma by imaging mass spectrometry: Development and validation of a melanoma prediction model.

BACKGROUND: The definitive diagnosis of melanocytic neoplasia using solely histopathologic evaluation can be challenging. Novel techniques that objectively confirm diagnoses are needed. This study details the development and validation of a melanoma prediction model from spatially resolved multivariate protein expression profiles generated by imaging mass spectrometry (IMS). METHODS: Three board-certified dermatopathologists blindly evaluated 333 samples. Samples with triply concordant diagnoses were included in this study, divided into a training set (n = 241) and a test set (n = 92). Both the training and test sets included various representative subclasses of unambiguous nevi and melanomas. A prediction model was developed from the training set using a linear support vector machine classification model. RESULTS: We validated the prediction model on the independent test set of 92 specimens (75 classified correctly, 2 misclassified, and 15 indeterminate). IMS detects melanoma with a sensitivity of 97.6% and a specificity of 96.4% when evaluating each unique spot. IMS predicts melanoma at the sample level with a sensitivity of 97.3% and a specificity of 97.5%. Indeterminate results were excluded from sensitivity and specificity calculations. CONCLUSION: This study provides evidence that IMS-based proteomics results are highly concordant to diagnostic results obtained by careful histopathologic evaluation from a panel of expert dermatopathologists.

The utility of PRAME immunohistochemistry in the evaluation of challenging melanocytic tumors.

BACKGROUND: PRAME (PReferentially expressed Antigen in Melanoma) immunohistochemistry has demonstrated high specificity for unequivocal melanomas; however, its utility in ambiguous melanocytic neoplasms has yet to be fully elucidated. METHODS: Cases of challenging melanocytic neoplasms were subclassified into one of three categories: challenging, favor benign (FB), challenging, cannot be subclassified (CCS), or challenging, favor malignant (FM). Using a previously published system, whereby cases with diffuse staining (>75%) were considered positive, scoring of PRAME was performed. Additionally, tumors with hotspot staining were also considered positive. RESULTS: Sixteen out of 85 tumors showed positive staining representing 5% of FB tumors, 24% of CCS tumors, and 47% of FM. In FB and CCS tumors, positive staining was mainly encountered in atypical intraepidermal melanocytic proliferations and spitzoid neoplasms. The specificity of positive PRAME staining was 95% and its concordance with the final diagnostic interpretation was 75%. CONCLUSIONS: PRAME positivity is more common in neoplasms favored to be malignant by histopathologic evaluation. Its clinical utility may include early diagnosis of incipient melanoma in situ. Rarely, benign melanocytic neoplasms could show diffuse expression of PRAME, and additional studies are needed to determine optimal utilization. Lastly, hotspot staining may increase its sensitivity without much compromise in specificity.

Extranodal NK/T-cell lymphoma primarily presenting as two adjacent slowly growing skin nodules with prominent epidermotropism and CD30 expression, a case report and review of literature.

Extranodal NK/T-cell lymphoma (NKTCL) is a rarely occurring non-Hodgkin lymphoma with predilection for the nasal cavity. Cutaneous involvement, rarely occurring and often aggressive in behavior, may present as nodular mass-forming lesions with or without ulceration. Histologically, lesions are characterized by an atypical dermal lymphoid infiltrate with angioinvasion and associated necrosis. Fortuitously, Epstein-Barr virus (EBV) infection, implicated in the pathogenesis of this entity, serves as a useful diagnostic marker (i.e. EBER in situ hybridization). We present a 54-year-old-man who initially presented with two ulcerations on the right lower leg which progressed despite antibiotic therapy. Histologic examination demonstrated dense lymphoid infiltrates exhibiting epidermotropism, angiocentricity and angioinvasion extending into the deep dermis. Immunohistochemical staining demonstrated expression of CD2, CD3, CD8, TIA-1, perforin, and granzyme-B, consistent with a cytotoxic T-cell phenotype. Additionally, CD56 was positive, confirming the presence of a coexistent NK cell phenotype. Testing also demonstrated significant CD30 expression, and molecular analysis was positive for TCR gene rearrangement. These findings, in conjunction with EBER in situ hybridization positivity, confirmed a diagnosis of extranodal NKTCL. We aim to increase awareness of this rarely occurring lymphoma with cutaneous involvement. CD30 expression in NKTCL raises the possibility of targeted treatment with brentuximab.

An unusual presentation of cutaneous histoplasmosis as a recurrent solitary and spontaneously healing lesion in an immunocompetent patient.

Infection with Histoplasma capsulatum typically manifests as a self-limiting pulmonary disease in immunocompetent patients. Systemic symptoms such as cutaneous lesions are associated with immunodeficient states. Our patient was an immunocompetent 68-year-old male who presented with a plaque on his left infraorbital area that was concerning for malignancy. Histological examination of the lesion revealed granulomatous inflammation and small yeast forms suggestive of H. capsulatum. The lesion resolved spontaneously and recurred 1 year later. On recurrence, histological examination again revealed yeast forms consistent with H. capsulatum. Serum and urine testing for H. capsulatum antigen were negative. Next-generation sequencing detected H. capsulatum, which supported the diagnosis of a cutaneous infection. The patient was prescribed and started treatment with itraconazole for 1 year after recurrence of the lesion, and he has not reported further disease recurrence to date. This case is unique because of the presentation of a primary cutaneous recurrent H. capsulatum lesion, and it demonstrated the utility of laboratory testing in its diagnosis.

A case of vancomycin-induced drug rash with eosinophilia and systemic symptoms (DRESS) syndrome with failure to respond to cyclosporine treatment.

Drug rash with eosinophilia and systemic symptoms (DRESS) is a rare delayed drug reaction that often occurs 2-6 weeks after initiation of therapy and may develop into a life-threatening systemic reaction. Besides immediate discontinuation of the suspected inciting drug, initiation of high dose systemic corticosteroids has long been the mainstay of treatment for severe cases. Nevertheless, significant drawbacks associated with systemic corticosteroid therapy, such as the requirement of a long tapering period post resolution and extensive adverse side effects profile, have motivated clinicians to seek alternative treatment options. Over the past decade, an undisputed increasing number of favorable case reports has highlighted cyclosporine as an emerging, safe, and effective alternative despite inconsistent dosing regimens reported. Herein, we report a severe case of vancomycin-induced DRESS syndrome in which the patient failed initial intervention with cyclosporine and needed rescue with methylprednisolone. To the best of our knowledge, this constitutes the first unsuccessful report of cyclosporine treatment for DRESS syndrome.