What's Eating You? Caterpillars.

Caterpillar envenomation is a worldwide problem, with manifestations ranging from dermatitis to iridocyclitis and a fatal hemorrhagic diathesis. This article focuses on the diagnosis and management of dermatoses related to caterpillars.

Morphea after Borrelia-induced facial nerve palsy.

Morphea, also known as localized scleroderma, is characterized by inflammation and fibrosis of the skin. The exact pathogenesis of morphea is unknown, but generally includes genetic predisposition to autoimmunity combined with an environmental insult. Previous cases have been associated with active Borrelia infection; however, Borrelia infection as a direct cause of morphea was not generalizable to most patients. Within endemic areas, Borrelia burgdorferi is the most common cause of facial nerve paralysis, another autoimmune phenomenon. We report a case of facial morphea in a young man with family history of autoimmune disease who developed morphea in the same location as two previous episodes of Borrelia-induced facial nerve palsy. This case is remarkable because it suggests Borrelia burgdorferi induced loss of local immune tolerance to host antigens, first with facial nerve palsy and followed years later by development of morphea.

Cutaneous Involvement by Mantle Cell Lymphoma: Expanding the Spectrum of Histopathologic Findings in a Series of 9 Cases.

Mantle cell lymphoma (MCL) is an aggressive B-cell neoplasm with cutaneous involvement in ∼1% of cases. We present a single institutional series of nine patients (12 specimens) with cutaneous involvement by systemic MCL and review the clinicopathologic features. Six males and 3 females (age range 55-87 years) were included. Sites of involvement were head and neck (n = 3), trunk (n = 5), and extremities (n = 4). Histopathologically, 3 showed classic cytomorphology, 2 were blastoid, 3 pleomorphic, and 1 showed features resembling marginal zone lymphoma. Two cases presented with cutaneous lesions as the first tissue manifestation of the disease. A second malignancy was identified in 3/9 cases (2 melanomas and 1 papillary thyroid carcinoma). In one patient, MCL was juxtaposed with metastatic melanoma within the same biopsy specimen. Fluorescence in situ hybridization studies, when available, demonstrated the characteristic t(11,14) translocation. Direct immunofluorescence was performed on one case and showed immunoglobulin M (IgM) expression on the tumor cells. Follow-up was available in 7 cases (mean 42 months, range 6-78 months) and revealed death from disease for 6 patients that occurred within 1 week to 11 months (mean 4 months) after cutaneous involvement. In our series, 6/9 cases demonstrated blastoid, pleomorphic, or marginal zone lymphoma-like morphologies that could potentially mimic other hematolymphoid neoplasms. MCL may show surface IgM expression on DIF or may occur in association with other solid tumors. Immunohistochemistry for cyclin D1 and/or SOX-11 may be helpful for diagnosis, and imaging studies may be necessary to detect systemic involvement when cutaneous involvement is the first manifestation of the disease.

High-throughput quantitative histology in systemic sclerosis skin disease using computer vision.

BACKGROUND: Skin fibrosis is the clinical hallmark of systemic sclerosis (SSc), where collagen deposition and remodeling of the dermis occur over time. The most widely used outcome measure in SSc clinical trials is the modified Rodnan skin score (mRSS), which is a semi-quantitative assessment of skin stiffness at seventeen body sites. However, the mRSS is confounded by obesity, edema, and high inter-rater variability. In order to develop a new histopathological outcome measure for SSc, we applied a computer vision technology called a deep neural network (DNN) to stained sections of SSc skin. We tested the hypotheses that DNN analysis could reliably assess mRSS and discriminate SSc from normal skin. METHODS: We analyzed biopsies from two independent (primary and secondary) cohorts. One investigator performed mRSS assessments and forearm biopsies, and trichrome-stained biopsy sections were photomicrographed. We used the AlexNet DNN to generate a numerical signature of 4096 quantitative image features (QIFs) for 100 randomly selected dermal image patches/biopsy. In the primary cohort, we used principal components analysis (PCA) to summarize the QIFs into a Biopsy Score for comparison with mRSS. In the secondary cohort, using QIF signatures as the input, we fit a logistic regression model to discriminate between SSc vs. control biopsy, and a linear regression model to estimate mRSS, yielding Diagnostic Scores and Fibrosis Scores, respectively. We determined the correlation between Fibrosis Scores and the published Scleroderma Skin Severity Score (4S) and between Fibrosis Scores and longitudinal changes in mRSS on a per patient basis. RESULTS: In the primary cohort (n = 6, 26 SSc biopsies), Biopsy Scores significantly correlated with mRSS (R = 0.55, p = 0.01). In the secondary cohort (n = 60 SSc and 16 controls, 164 biopsies; divided into 70% training and 30% test sets), the Diagnostic Score was significantly associated with SSc-status (misclassification rate = 1.9% [training], 6.6% [test]), and the Fibrosis Score significantly correlated with mRSS (R = 0.70 [training], 0.55 [test]). The DNN-derived Fibrosis Score significantly correlated with 4S (R = 0.69, p = 3 × 10- 17). CONCLUSIONS: DNN analysis of SSc biopsies is an unbiased, quantitative, and reproducible outcome that is associated with validated SSc outcomes.

Lobular neutrophilic panniculitis associated with DNA methyltransferase inhibitors in the treatment of myeloid disease.

Cutaneous toxicities to DNA methyltransferase inhibitors are variable and include localized injection site reactions, ecchymoses, maculopapular eruptions, and neutrophilic dermatoses including pyoderma gangrenosum, Sweet syndrome, and neutrophilic eccrine hidradenitis. This series describes two patients diagnosed with lobular neutrophilic panniculitis arising during treatment of acute myelogenous leukemia with "hypomethylating drugs," including the first report of its occurrence with a next-generation agent. Differential diagnoses, histopathologic characteristics, treatment considerations, and proposed pathogenesis will be discussed.

Pathology of spontaneous and immunotherapy-induced tumor regression in a murine model of melanoma.

We evaluated the spontaneous and immunotherapy-induced histological changes in the tumor microenvironment of a mouse melanoma regression model consisting of immunocompetent C57BL/6J mice implanted with syngeneic YUMMER1.7 melanoma cells. We focused on tumor regression phenotypes and spatial relationships of melanoma cells with B cells and neutrophils since this was not previously described. We found common themes to the host response to cancer irrespective of the mode of tumor regression. In nonregression tumors, melanoma cells were epithelioid shaped and tightly packed. In regression tumors, melanoma cells were spindle shaped and discohesive. B cells including plasmablasts and plasma cells were numerous and were increased with immunotherapy. Neutrophils were in direct contact with dead or dying melanoma cells. Immunotherapy increased neutrophil counts and induced neutrophil extracellular traps (NETs)-like formations and geographic necrosis. Beyond tumor regression, the increase in the B cell and neutrophil response could play a role in immunotherapy-induced adverse reactions.

Detection of Borrelia in Ixodes scapularis ticks by silver stain, immunohistochemical and direct immunofluorescent methods.

BACKGROUND: Lyme disease (LD) is one of the most common tick-borne diseases caused by several Borrelia species of spirochetes. Ixodes scapularis is responsible for the transmission of LD in the northeastern United States. The rate of infection varies with the duration of tick attachment to the host; however, this information may be unknown. In skin biopsies, it is often difficult to identify spirochetes. Testing of ticks is not routinely performed. Treatment is established by clinical presentation. OBJECTIVE: To test paraffin-embedded I. scapularis ticks for Borrelia by different methods. MATERIALS/METHODS: We examined 20 paraffin-embedded ticks by silver stain, immunohistochemical (IHC) and direct immunofluorescent (DIF) methods and compared the percentage of positivity with DIF results from the Connecticut Agricultural Experiment Station. RESULTS: The results were similar by DIF, which proved to be the most sensitive method, followed by the silver stain and IHC. CONCLUSION: We found that the identification of spirochetes in paraffin-embedded ticks was less difficult than in tissue with a comparable turnaround time to that of a routine biopsy. Timely identification of Borrelia in ticks may influence the clinical management of the patients.

How to take better photomicrographs: A step-wise approach.

The objective of our study was to establish a detailed photomicrographing protocol for pathologists and dermatopathologists using standard overhead camera and image editing packages. Through a trial-and-error approach we devised a series of steps that comprise our photomicrographing protocol. Descriptive and interpretive data analyses were performed to highlight how each step improves tinctorial quality of digital photomicrographs.