A CD56- immunoblastoid variant of blastic plasmacytoid dendritic cell neoplasm.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive malignant hematologic neoplasm arising from plasmacytoid dendritic cells. It is a very rare tumor that constitutes less than 0.1% of all hematologic malignancies. Most patients with BPDCN present clinically with cutaneous lesions as the first sign of disease. Immunophenotypic variability with aberrant marker profiles has been reported. We report a case of a transcription factor 4 (TCF-4) + BPDCN, with negative CD56 expression in an 85-year-old woman with multiple skin nodules. A punch biopsy revealed a diffuse, monomorphous, and non-epidermotropic cell infiltrate involving the entire dermis. The infiltrate was composed of intermediate-sized cells with immunoblastoid morphology, which is an unusual morphologic variant. The neoplastic cells were strongly positive for CD45 and co-expressed CD4, CD123, TCF-4, BCL-2, and CD10. The Ki-67 proliferative rate was very high (90%). Negative immunostains included CD56, an unusual finding in BPDCN. This case illustrates the challenges encountered in the diagnosis of this entity, particularly in unusual morphologic variants and phenotypes. The elucidation of molecular signatures and development of targeted therapies for its management have been recently introduced and differ from acute myeloid leukemias. Hence, accurate diagnosis of BPDCN is critical for dermatopathologists.

High-fidelity detection, subtyping, and localization of five skin neoplasms using supervised and semi-supervised learning.

Background: Skin cancers are the most common malignancies diagnosed worldwide. While the early detection and treatment of pre-cancerous and cancerous skin lesions can dramatically improve outcomes, factors such as a global shortage of pathologists, increased workloads, and high rates of diagnostic discordance underscore the need for techniques that improve pathology workflows. Although AI models are now being used to classify lesions from whole slide images (WSIs), diagnostic performance rarely surpasses that of expert pathologists. Objectives: The objective of the present study was to create an AI model to detect and classify skin lesions with a higher degree of sensitivity than previously demonstrated, with potential to match and eventually surpass expert pathologists to improve clinical workflows. Methods: We combined supervised learning (SL) with semi-supervised learning (SSL) to produce an end-to-end multi-level skin detection system that not only detects 5 main types of skin lesions with high sensitivity and specificity, but also subtypes, localizes, and provides margin status to evaluate the proximity of the lesion to non-epidermal margins. The Supervised Training Subset consisted of 2188 random WSIs collected by the PathologyWatch (PW) laboratory between 2013 and 2018, while the Weakly Supervised Subset consisted of 5161 WSIs from daily case specimens. The Validation Set consisted of 250 curated daily case WSIs obtained from the PW tissue archives and included 50 "mimickers". The Testing Set (3821 WSIs) was composed of non-curated daily case specimens collected from July 20, 2021 to August 20, 2021 from PW laboratories. Results: The performance characteristics of our AI model (i.e., Mihm) were assessed retrospectively by running the Testing Set through the Mihm Evaluation Pipeline. Our results show that the sensitivity of Mihm in classifying melanocytic lesions, basal cell carcinoma, and atypical squamous lesions, verruca vulgaris, and seborrheic keratosis was 98.91% (95% CI: 98.27%, 99.55%), 97.24% (95% CI: 96.15%, 98.33%), 95.26% (95% CI: 93.79%, 96.73%), 93.50% (95% CI: 89.14%, 97.86%), and 86.91% (95% CI: 82.13%, 91.69%), respectively. Additionally, our multi-level (i.e., patch-level, ROI-level, and WSI-level) detection algorithm includes a qualitative feature that subtypes lesions, an AI overlay in the front-end digital display that localizes diagnostic ROIs, and reports on margin status by detecting overlap between lesions and non-epidermal tissue margins. Conclusions: Our AI model, developed in collaboration with dermatopathologists, detects 5 skin lesion types with higher sensitivity than previously published AI models, and provides end users with information such as subtyping, localization, and margin status in a front-end digital display. Our end-to-end system has the potential to improve pathology workflows by increasing diagnostic accuracy, expediting the course of patient care, and ultimately improving patient outcomes.

A case of reed syndrome with a novel mutation in the fumarate hydratase gene.

Reed syndrome is a heritable cancer predisposition syndrome that can easily be missed due to its simple presentation of tender red papules. We present a young female with a history of uterine fibroids who presented to the dermatology clinic with several painful pink papules that had been previously evaluated by multiple physicians. Biopsy results were diagnostic for cutaneous leiomyomas, raising clinical suspicion for Reed syndrome. She was found to have a novel heterozygote mutation in her fumarate hydratase gene, supporting the diagnosis. This case demonstrates the importance of rendering a proper workup for seemingly innocent skin complaints as they could be associated with an underlying malignancy. Despite the fact that up to 16% of patients can develop aggressive type 2 papillary renal cell carcinoma, there are currently no consensus guidelines on screening or patient management.

Adverse events following smallpox vaccination with ACAM2000 in a military population.

BACKGROUND: Generalized vaccinia and benign exanthems are 2 adverse events that have been associated with the smallpox vaccination. Accurate incidence and prevalence rates of each are not readily available, but these events are thought to be uncommon. To our knowledge, this is the first case series to provide clinical as well as pathologic descriptions of multiple papulovesicular eruptions occurring after receiving the second-generation smallpox vaccine, ACAM2000 (Acambis, Canton, Massachusetts), among a vaccinia-naïve military population. In addition, we report the first confirmed case, to our knowledge, of generalized vaccinia following administration of the ACAM2000 vaccine. OBSERVATIONS: All patients received primary smallpox immunization as well as 1 to 3 concurrent or near-concurrent (within the preceding 21 days) immunizations for typhoid, anthrax, hepatitis B, and/or seasonal influenza. One patient presented with a flulike prodrome and diffuse vesiclopustules covering the face, neck, chest, back, and upper and lower extremities. Vaccinia polymerase chain reaction confirmed generalized vaccinia. The remaining 7 patients presented with unusual, painful, and pruritic papulovesicular eruptions occurring on the extensor surfaces of their upper and lower extremities without systemic symptoms. Histologic findings revealed 2 general patterns, including a dermal hypersensitivity reaction with lymphocytic vasculitis and a vesicular spongiotic dermatitis with eosinophils. CONCLUSIONS: We present the first confirmed case of generalized vaccinia following immunization with the second-generation smallpox vaccine ACAM2000. In addition, we describe 7 cases of benign, acral, papulovesicular eruptions thought to be associated with ACAM2000 administration. Further research is needed to discern the pathogenesis of these benign eruptions as well as their incidence and prevalence and that of generalized vaccinia with ACAM2000.

Laboratory assistive personnel in Mohs micrographic surgery: a survey of training and laboratory practice.

BACKGROUND: The success of Mohs micrographic surgery (MMS) is contingent on high-quality frozen tissue sections for histologic interpretation. Laboratory assistive personnel (LAP) are central to this process, but their training and tissue processing techniques are neither standardized nor certified for competence. OBJECTIVE: To evaluate processes used to train and laboratory techniques practiced by LAP. Letters were mailed to Mohs surgeons with a Web link to an online survey for LAP to complete. RESULTS: Response rate was 24%. Responders primarily received training on the job, but not from the surgeon. On-the-job training from other LAP was perceived to be the most helpful, and textbook to be the least helpful. On average, survey responders felt it took several months to become proficient. Wide variations in laboratory practice were noted for histology laboratory and Mohs tissue processing techniques and for quality assurance. Differences in training and practices were noted between certified and noncertified LAP. CONCLUSION: Patient care may be compromised because of variable practice of laboratory techniques, quality assurance, and quality control. Standardization of LAP training, along with demonstration and maintenance of competency, may be necessary to ensure the integrity of the MMS technique.

Significance of tertiary Gleason pattern 5 in Gleason score 7 radical prostatectomy specimens.

PURPOSE: The Gleason grading system in reporting prostate cancer accounts for the primary and secondary Gleason pattern. The clinical significance of a higher tertiary (third most prevalent) grade is largely unrecognized. MATERIALS AND METHODS: Radical prostatectomy specimens from 300 patients with Gleason score 7 (3 + 4 or 4 + 3) prostate cancer were pathologically reexamined for the presence of a tertiary grade 5 pattern as well as the association with pathological stage and biochemical recurrence-free survival. RESULTS: A total of 214 patients met study inclusion criteria. Patients with Gleason score 7 and tertiary grade 5 cancer had significantly higher pathological stage disease than patients with Gleason score 7 without tertiary grade 5 cancer (p <0.001). Gleason score 7 + tertiary pattern 5 tumors were significantly associated with adverse pathological features such as seminal vesicle invasion, extraprostatic extension and lymphovascular invasion compared to Gleason score 7 tumors (p <0.05). The relative effects of a tertiary grade 5 component on all pathological parameters analyzed was greater for Gleason score 7 tumors with a lower primary Gleason pattern 3 vs a higher primary Gleason pattern 4. Patients with Gleason score 7 + tertiary pattern 5 tumors had significantly decreased biochemical recurrence-free survival (54 months) compared to patients with Gleason score 7 tumors (121 months) (p = 0.0005). Preoperative prostate specific antigen, lymphovascular invasion and positive surgical margin status were shown to be independent predictors of prostate specific antigen recurrence on multivariate analysis. CONCLUSIONS: Small percentages of tertiary grade 5 patterns in Gleason score 7 radical prostatectomy specimens are associated with aggressive pathological features predictive of advanced pathological stage and biochemical recurrence-free survival.

Strongyloides stercoralis hyperinfection in a patient with rheumatoid arthritis after anti-TNF-alpha therapy.

Strongyloidiasis is epidemic in tropical and subtropical regions where the regional prevalence may exceed 25%. In the United States, highest infection rates are found in immigrants. Many infected individuals are asymptomatic, whereas others may have mild and nonspecific cutaneous, intestinal, and pulmonary symptoms. Strongyloides stercoralis may remain as a dormant infection, but replication and dissemination can be fatal in immunocompromised patients. We report on a 63-year-old native Filipino man with a history of rheumatoid arthritis who developed Escherichia coli sepsis, filariform larvae characteristic of S. stercoralis bronchoalveolar lavage, and adult respiratory distress syndrome 3 weeks after he presented with vague gastrointestinal symptoms. We believe that the addition of a tumor necrosis factor (TNF)-alpha inhibitor to his treatment with prednisone and methotrexate for rheumatoid arthritis further suppressed his cellular immunity leading to hyperinfection and life-threatening S. stercoralis infection. This is another, often latent, infection that should be considered in patients in or from endemic areas before institution of antitumor necrosis factor therapy.

Primary extraneural myxopapillary ependymoma of the broad ligament.

Primary extraneural ependymomas are rare tumors that arise in ectopic sites, including pulmonary, sacrococcygeal region, ovarian, and paraovarian tissues. Four such ependymomas reported in the literature involve the paraovarian tissues, including 2 broad ligament ependymomas. Here we describe a myxopapillary ependymoma of the broad ligament in a 22-year-old woman, which may be the first tumor of this type to be reported in this location. Cytology, histology, cytochemistry, immunohistochemistry, and flow cytometry ploidy analysis are studied and described. Identification of perivascular ependymal rosettes, ependymal canals, vimentin and glial fibrillary acidic protein immunoreactivity, cytochemical staining of blepharoplasts or terminal bars by phosphotungstic acid hematoxylin, and presence of multiple foci of myxoid degeneration among the ependymal rosettes characterized a myxopapillary ependymoma.