A Comparison of Tenosynovial and Transverse Carpal Ligament Biopsy for Amyloid Detection in Open Carpal Tunnel Release.

PURPOSE: Our purpose was to compare differences in the incidence of amyloid deposition in tenosynovium (TS) versus transverse carpal ligament (TCL) biopsies obtained during open carpal tunnel release. We hypothesized that the incidence of amyloid would be similar between TCL and TS when obtaining both specimens from the same patient. METHODS: All primary, elective open carpal tunnel release cases that underwent biopsy for amyloid between January 2022 and September 2023 were reviewed. Tenosynovial and TCL specimens were independently evaluated by a pathologist to assess for amyloid. Demographic data were collected, and incidence of amyloid deposition was compared between the two samples. Agreement statistics, sensitivity, and specificity were calculated for TCL, using TS as the reference standard. RESULTS: A total of 196 cases met either Tier 1 (n=180) or Tier 2 (n=16) biopsy criteria. Forty-eight cases were excluded for missed biopsies or laboratory processing errors, leaving 148 cases available for analysis. Amyloid deposition was present in 31 out of 148 (21%) TS specimens and 33 out of 148 (22%) TCL specimens. Overall, the results of the TS biopsy agreed with TCL biopsy in 138 out of 148 cases (93%). In the 10 cases for which the results of the TCL and TS biopsy differed, six cases had (+) TCL and (-) TS, and four cases had amyloid deposition in TS without evidence of deposition in the TCL. Sensitivity and specificity values for the TCL specimen were 87% and 95%, respectively. Positive and negative predictive values were 82% and 97%, respectively. CONCLUSIONS: For cases of open carpal tunnel release undergoing biopsy, amyloid deposition was noted in 21% of TS specimens and 22% of TCL specimens. Results of TS and TCL biopsies obtained from the same patient agreed in 93% of cases. Single-source biopsy for amyloid represents a reasonable diagnostic approach. Future cost analyses should be performed to determine whether the addition of two biopsy sources to improve diagnostic accuracy is justified. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Utility of artificial intelligence in a binary classification of soft tissue tumors.

Soft tissue tumors (STTs) pose diagnostic and therapeutic challenges due to their rarity, complexity, and morphological overlap. Accurate differentiation between benign and malignant STTs is important to set treatment directions, however, this task can be difficult. The integration of machine learning and artificial intelligence (AI) models can potentially be helpful in classifying these tumors. The aim of this study was to investigate AI and machine learning tools in the classification of STT into benign and malignant categories. This study consisted of three components: (1) Evaluation of whole-slide images (WSIs) to classify STT into benign and malignant entities. Five specialized soft tissue pathologists from different medical centers independently reviewed 100 WSIs, representing 100 different cases, with limited clinical information and no additional workup. The results showed an overall concordance rate of 70.4% compared to the reference diagnosis. (2) Identification of cell-specific parameters that can distinguish benign and malignant STT. Using an image analysis software (QuPath) and a cohort of 95 cases, several cell-specific parameters were found to be statistically significant, most notably cell count, nucleus/cell area ratio, nucleus hematoxylin density mean, and cell max caliper. (3) Evaluation of machine learning library (Scikit-learn) in differentiating benign and malignant STTs. A total of 195 STT cases (156 cases in the training group and 39 cases in the validation group) achieved approximately 70% sensitivity and specificity, and an AUC of 0.68. Our limited study suggests that the use of WSI and AI in soft tissue pathology has the potential to enhance diagnostic accuracy and identify parameters that can differentiate between benign and malignant STTs. We envision the integration of AI as a supportive tool to augment the pathologists' diagnostic capabilities.

A Comparison of Amyloid Deposition in Endoscopic and Open Carpal Tunnel Release.

PURPOSE: Previous investigations assessing the incidence of amyloidosis detected with biopsy during carpal tunnel release (CTR) have focused on open CTR (OCTR). Prior authors have suggested that biopsy may be more technically challenging during endoscopic carpal tunnel release (ECTR). Our purpose was to compare differences in the incidence of amyloid deposition detected during ECTR versus OCTR. METHODS: We reviewed all primary ECTR and OCTR during which a biopsy for amyloid was obtained between February 2022 and June 2023. All procedures were performed by five upper-extremity surgeons from a single institution. Congo red staining was used to determine the presence of amyloid deposition in either the transverse carpal ligament (TCL) or tenosynovium. All positive cases underwent subtype analysis and protein identification through liquid chromatography-tandem mass spectrometry. Baseline demographics were recorded for each case, and the incidence of positive biopsy was compared between ECTR and OCTR cases. RESULTS: A total of 282 cases were included for analysis (143 ECTR and 139 OCTR). The mean age was 67 years, and 45% of cases were women. Baseline demographics were similar except for a significantly higher incidence of diabetes in OCTR cases (13% vs 33%). Overall, 13% of CTR cases had a positive biopsy. There was a statistically significant difference in the incidence of amyloid deposition detected during biopsy in ECTR cases (3.5%) compared with OCTR cases (23%). CONCLUSIONS: Biopsy performed during ECTR may result in a lower incidence of amyloid detection. Future basic science investigation may be necessary to determine histologic differences between tenosynovium proximal and distal to the leading edge of the TCL. When surgeons plan a biopsy during surgical release of the carpal tunnel, an open approach may be advantageous. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Immunohistochemistry Update in Dermatopathology and Bone and Soft Tissue Pathology.

CONTEXT.­: Immunohistochemistry plays an important role in dermatopathology, particularly for melanocytic lesions and poorly differentiated malignancies. In the field of bone and soft tissue pathology, molecular methods remain the gold standard for diagnosis; however, immunohistochemistry targeting underlying molecular alterations represents a valuable screening tool, especially in areas with limited access to molecular testing. OBJECTIVE.­: To describe the utility and limitations of new and emerging immunohistochemical stains in the diagnosis of skin, soft tissue, and bone tumors. DATA SOURCES.­: A literature review of recently described immunohistochemical stains in the fields of dermatopathology and bone and soft tissue pathology was performed. CONCLUSIONS.­: Immunohistochemistry is an important adjunctive tool for select entities in dermatopathology and bone and soft tissue pathology, and it provides pathologists with valuable evidence of their behavior, underlying molecular alterations, and line of differentiation. Furthermore, immunostains targeting molecular abnormalities have the potential to replace current molecular methods. Many of these recently described stains demonstrate higher sensitivity and specificity; however, limitations and pitfalls still exist, and correlation with morphologic and clinical findings remains essential for diagnosis.

Partnership in Cancer Research (PCAR) Program Increases Medical Student Knowledge and Confidence to Perform Cancer Research.

Arkansas has a high cancer burden, and a pressing need exists for more medical students to pursue oncology as a career. The Partnership in Cancer Research (PCAR) program provides a summer research experience at the University of Arkansas for Medical Sciences for 12 medical students who have completed their first year of medical training. A majority of participants spend time pursuing cancer research in basic science, clinical, or community-based research. Students report on their research progress in an interactive "Live from the Lab!" series and assemble a final poster presentation describing their findings. Other activities include participation in a moderated, cancer-patient support group online, lecture series on cancer topics, medical simulations, palliative care clinic visit, "Death Over Dinner" event, and an entrepreneurship competition. Students completed surveys over PCAR's first 2 years in operation to evaluate all aspects of the program. Surveys reveal that students enthusiastically embraced the program in its entirety. This was especially true of the medical simulations which received the highest evaluations. Most significantly, surveys revealed that the program increased cancer knowledge and participant confidence to perform cancer research.

Primary Epithelioid Sarcoma of the Conchal Bowl in a 64-Year-Old Male: A Case Report and Review of the Literature.

ABSTRACT: Epithelioid sarcoma (ES) is a distinctive malignant mesenchymal neoplasm with atypical epithelioid cells palisading around a central zone of necrosis. ES is a rare entity even in soft tissue pathology. Immunohistochemically, tumors usually show diffuse epithelial membrane antigen and cytokeratin expression and loss of nuclear INI1 (SMARCB1) expression. Here, we report a case of a 64-year-old man with ES arising in the left conchal bowl. Given the clinical presentation including patient's age, sun-exposed area of skin, and slow-growing, asymptomatic, small pink pearly papule, this patient was initially misdiagnosed with basal cell carcinoma clinically and treated with topical imiquimod at an outside facility. The lesion continued to grow and eventually became symptomatic despite the treatment after which biopsy was obtained. Despite the unusual anatomic site and the patient's age, the microscopic and immunohistochemical findings were characteristic of conventional-type ES. Our case shows that ES can arise in rare locations and in older adults where it may be more easily misdiagnosed clinically and pathologically as a nonmelanoma skin cancer.

Kaposi Sarcoma in Afghanistan: A Case Series from a Tertiary Referral Center.

Kaposi sarcoma is a vascular endothelial neoplasm caused by human herpesvirus 8. Although it is a well-studied disease, little is known about the specific characteristics or epidemiology of Kaposi sarcoma in Afghanistan. The data consist primarily of anecdotal reports and epidemiological studies extrapolated from neighboring countries. In this case series, we summarize existing data about Kaposi sarcoma in Afghanistan and present seven histologically confirmed cases with associated clinical features to shed light on the characteristics of Kaposi sarcoma in this unique geographic setting.

Primary Cutaneous Alveolar Rhabdomyosarcoma in an Elderly Adult: A Rare Potential Mimic of Merkel Cell Carcinoma.

ABSTRACT: Rhabdomyosarcoma (RMS) rarely arises as a primary skin tumor. It is also very rare in older adults, especially the alveolar type. We report an 80-year-old White woman who presented with a painful, erythematous, raised lesion (2 × 3.5 cm) above the left knee that was fixed within the skin, yet mobile about underlying soft tissue. A punch biopsy showed monotonous malignant round blue cells involving the dermis. Immunostains showed diffuse expression of CD56, focal chromogranin, focal dot-like pancytokeratin, CK7, and neurofilament, but negative for synaptophysin, CK20, SOX-10, MUM-1, CD43, TTF-1, and CD99. A CK20-negative variant of Merkel cell carcinoma was initially favored, but given the unusual immunophenotype and the presence of cellular dyscohesion, desmin and myogenin stains were performed, both of which were diffusely positive. Molecular testing revealed rearrangement of PAX3 and FOXO1 loci, confirming the diagnosis of alveolar RMS. PET/CT showed a probable 1.9-cm left inguinal lymph node metastasis; no internal or deep soft tissue primary tumor mass was identified, supporting a true primary cutaneous origin. Alveolar RMS may express keratins and neuroendocrine markers, making it easy to confuse with Merkel cell carcinoma on those exceptionally rare instances, when it arises in the skin of older adults.

Dermatofibrosarcoma protuberans with platelet-derived growth factor-D rearrangement; two cases with morphologically distinct presentations.

Dermatofibrosarcoma protuberans (DFSP) is a mesenchymal neoplasm that is usually located in the dermis or subcutis and is locally aggressive. Rarely, these lesions may undergo fibrosarcomatous transformation, which is thought to increase their metastatic potential. DFSP is classically associated with a 17;22 translocation (or ring chromosome thereof) resulting in fusion of the COL1A1 and PDGFB genes. However, variant fusions involving PDGFD have been recently reported. Herein, we present two morphologically diverse cases of DFSP with PDGFD rearrangement. Case 1 is a 68-year-old female with a left dorsal foot lesion. Morphologically, the lesion is unusual as it is a well-circumscribed, hypercellular, subcutaneous nodule with uniform CD34-positive spindle cells arranged in a herringbone pattern without storiform arrangement or "honeycombing" fat entrapment. It was diagnosed as pure fibrosarcomatous DFSP. Case 2 is a 37-year-old male with a right supra-auricular lesion. Morphologically, the lesion displays classic DFSP features including bland CD34-positive spindle cells with storiform growth, fat entrapment, and infiltrative borders. Both lesions were negative for COL1A1-PDGFB fusion but positive for PDGFD rearrangement by fluorescence in situ hybridization (FISH) analysis. FISH testing for PDGFD rearrangement should be performed in cases where there is a high suspicion for DFSP but initial studies for COL1A1-PDGFB are negative.

Characterization of Morphologic and Cytochemical Staining Properties of Exogenous Materials Mimicking Fungal Organisms Encountered in Skin Biopsies.

BACKGROUND: Exogenous materials may be encountered in skin biopsies as contamination. Contamination may occur during the biopsy procedure in the clinic or during tissue processing in the laboratory. Although the experienced pathologist may often instinctively ignore clear examples of contamination, such tissue may be a source of confusion for young pathologists and those in training. Foreign materials can typically be recognized as exogenous by morphology, polarizability, and the presence or absence of a tissue reaction, but we have rarely encountered situations in which exogenous materials could be misinterpreted as organisms, either by their morphologic appearance or staining properties. METHODS: Exogenous materials used during skin biopsy and grossing were embedded in a nonhuman tissue scaffold and prepared into histologic slides. Hematoxylin and eosin (H&E), periodic acid-Schiff with diastase, and Grocott methenamine silver stains were performed, and each material was evaluated under polarized microscopy. RESULTS: Exogenous materials were divided into the following 3 categories with shared morphologic appearances and staining properties: suture materials, plant-based materials, and synthetic materials. CONCLUSION: We present a comprehensive characterization of the morphologic and cytochemical staining properties of multiple exogenous materials that may contaminate a skin biopsy. This characterization will aid the pathologist by providing a mechanism to identify potential contaminants in skin biopsies.

Multisite Quality Improvement Study of a Patient-Pathologist Consultation Program.

OBJECTIVES: The aim of this multisite quality improvement study was to evaluate patients' experiences with the patient-centered pathology (PCP) consultation program and to determine whether PCP enhanced their care experience. METHODS: Patients were invited to attend PCP consultations to review their pathology report and slides and have their questions answered by the pathologist privately, with the option to attend the appointment with family members or friends for support. A patient experience questionnaire (PEQ) was administered to patients, who participated voluntarily in the PCP, and survey data were collected and stored in REDCap. Statistical analysis was performed using SAS 9.4 (SAS Institute). RESULTS: Sixty-seven patients (95.5% female) aged 18 to 84 years across 4 institutions completed the PEQ. Overall, 58% and 15.8% of patients had breast and brain tumors, respectively, and 59.7% of tumors were newly diagnosed. Most patients thought it was important for them to learn as much as they could about their health condition. However, the majority of patients reported some degree of difficulty learning about their health condition based on written information, despite 97% having completed high school and/or further education. The majority of patients rated their pathologist as "excellent" across communication metrics. Ultimately, 100% of respondents were satisfied, found their visits to be useful, and would recommend the PCP to other patients. CONCLUSIONS: Patients found that personalized clinical encounters with pathologists improved their understanding of their health condition and their satisfaction with their care experience. Patients thought pathologists communicated respectfully, effectively, and empathetically.

Attitudes Toward Artificial Intelligence Within Dermatopathology: An International Online Survey.

Background: Artificial intelligence (AI) has recently surfaced as a research topic in dermatology and dermatopathology. In a recent survey, dermatologists were overall positive toward a development with an increased use of AI, but little is known about the corresponding attitudes among pathologists working with dermatopathology. The objective of this investigation was to make an inventory of these attitudes. Participants and Methods: An anonymous and voluntary online survey was prepared and distributed to pathologists who regularly analyzed dermatopathology slides/images. The survey consisted of 39 question divided in five sections; (1) AI as a topic in pathology; (2) previous exposure to AI as a topic in general; (3) applications for AI in dermatopathology; (4) feelings and attitudes toward AI and (5) self-reported tech-savviness and demographics. The survey opened on March 13, 2020 and closed on May 5, 2020. Results: Overall, 718 responders (64.1% females) representing 91 countries were analyzed. While 81.5% of responders were aware of AI as an emerging topic in pathology, only 18.8% had either good or excellent knowledge about AI. In terms of diagnosis classification, 42.6% saw strong or very strong potential for automated suggestion of skin tumor diagnoses. The corresponding figure for inflammatory skin diseases was 23.0% (Padj < 0.0001). For specific applications, the highest potential was considered for automated detection of mitosis (79.2%), automated suggestion of tumor margins (62.1%) and immunostaining evaluation (62.7%). The potential for automated suggestion of immunostaining (37.6%) and genetic panels (48.3%) were lower. Age did not impact the overall attitudes toward AI. Only 6.0% of the responders agreed or strongly agreed that the human pathologist will be replaced by AI in the foreseeable future. For the entire group, 72.3% agreed or strongly agreed that AI will improve dermatopathology and 84.1% thought that AI should be a part of medical training. Conclusions: Pathologists are generally optimistic about the impact and potential benefit of AI in dermatopathology. The highest potential is expected for narrow specified tasks rather than a global automated suggestion of diagnoses. There is a strong need for education about AI and its use within dermatopathology.

Prospective Consensus Reporting by Gynecologic Pathology and Dermatopathology Improves Diagnosis of Vulvar Biopsies.

CONTEXT.­: Vulvar biopsy interpretation and reporting, particularly of vulvar dermatoses, can be challenging in daily practice for both surgical pathologists (SPs) and dermatopathologists (DPs). OBJECTIVE.­: To investigate whether prospective consensus reporting of vulvar biopsies by SPs and DPs would provide value and improve overall diagnostic concordance. DESIGN.­: Consecutive vulvar biopsies during a 6-month period were reviewed prospectively by both gynecologic SPs and DPs. Preliminary, independently generated diagnoses were recorded and then shared in consensus review (SPs+DPs). A third pathologist adjudicated cases without consensus. Multiple data elements were collected for each case: division (SP/DP), age, site, clinical history, diagnostic category, preliminary and final (consensus) diagnosis, need for adjudication, ancillary tests, and diagnostic discrepancy. RESULTS.­: Eighty-four biopsies (48 SP, 36 DP) from 70 patients were reviewed. Forty-two of 84 cases (50%) were neoplastic, 38 of 84 (45%) were reactive/inflammatory, with the remaining (5%) showing both or other features. Independent diagnoses were discrepant in 22 of 84 cases (26%), but consensus review resulted in an agreed-upon diagnosis in all cases, with adjudication required in 6 cases. Independent diagnostic agreement increased over time with a reduction in major and minor discrepancies between the first and second half of the study period. CONCLUSIONS.­: Prospective review of vulvar biopsies by both SPs and DPs can improve overall reporting. Consensus review allows pathologists to gain diagnostic confidence in interpretation of inflammatory (for SPs) and neoplastic (for DPs) vulvar biopsies; therefore, intradepartmental consultation is of value, particularly in select cases.

Primary superficial Ewing sarcoma: A unique entity? A case report including novel findings of ELF3 and TNFRSF14 copy number loss.

Primary superficial Ewing sarcoma (psES) cases are exceedingly rare, with fewer than 150 cases reported in the literature. Small case series have suggested differences between psES and Ewing sarcoma (ES) of bone or deep soft tissues: psES appears to have a more indolent course and a higher 5-year overall survival rate. PsES is more common in older adolescent females as opposed to younger males in their peak growth velocity years in bone or deep soft tissue ES. We present a case report of a 17-year-old female with a relatively static nodule on her left thigh for 4 years. Morphologic, immunohistochemical, and molecular evaluations confirmed ES. Patient underwent a gross-total resection and a shortened course of adjuvant chemotherapy without radiation. Cancer gene panel testing found three gene abnormalities (in addition to EWSR1-FLI1 fusion): CCND1 copy number gain, ELF3 copy number loss, and TNFRSF14 copy number loss. To our knowledge, this is the first published case report of psES to include genomic sequencing and the first to report ELF3 and TNFRSF14 abnormalities in ES. Larger series of psES cases with genomic profiling are needed to elucidate a possible genetic etiology for its more indolent clinical course and favorable outcomes.

Elastophagocytosis and interstitial granulomatous infiltrate are more common in extragenital vs genital lichen sclerosus.

BACKGROUND: Genital and extragenital lichen sclerosus (LS) share similar histopathologic features. A recent small series documented elastophagocytosis uniquely in extragenital LS. We evaluated a larger series of LS for elastophagocytosis, elastic fiber loss, and other histopathologic features. We evaluated matrix metalloproteinase (MMP) expression to determine if these proteins play an etiologic role. METHODS: Genital (n = 42) and extragenital (n = 41) LS biopsies were examined for histopathologic features, elastic fiber alteration (Verhoeff van Gieson staining), and MMP-2 and MMP-9 expression (immunohistochemistry). RESULTS: Elastophagocytosis and an interstitial granulomatous pattern were significantly more common in extragenital LS than genital LS (43.9% vs 4.7% and 56.1% vs 9.5%). Extragenital LS had mild/focal elastic fiber loss (43.9%), while genital LS had moderate (61.9%) or marked (19%) loss. MMP-9 was diffusely expressed in histiocytes in both types of LS (genital 97.5%; extragenital 100%). Weak MMP-2 expression was seen in genital (58%) and extragenital (55%) LS. CONCLUSIONS: Extragenital LS, but not genital LS, frequently exhibits elastophagocytosis and interstitial granulomatous infiltrate, and these patterns could contribute to elastic fiber destruction in extragenital LS. While MMP-2 and MMP-9 expression are common in LS, expression did not significantly differ depending on anatomic site and thus is unlikely to explain observed histopathologic differences.

Hansen Disease (Leprosy) and Armadillo Exposure in Arkansas: A Case Series.

BACKGROUND: Although most cases of Hansen disease (HD) in the United States are imported from endemic areas, a subset of cases are relate to exposure to nine-banded armadillos. Several recent cases of HD in Arkansas occurred in patients who had not traveled to endemic areas and who reported variable degrees of armadillo exposure. OBJECTIVE: The purpose of this study was to report 6 cases of HD diagnosed in Arkansas between 2004 and 2016. The secondary purpose was to explore the correlation between exposure to the nine-banded armadillo as it pertains to transmission of the disease. METHODS: The referring clinician of each patient was contacted to gather information regarding the patient's clinical presentation, armadillo exposure, and travel history. In addition, the Arkansas Department of Health was consulted to review the demographics of individuals diagnosed with HD in the past 15 years and to review the distribution of HD throughout the state of Arkansas. RESULTS: Six domestic cases of HD were associated with both direct and indirect exposure to armadillos. LIMITATIONS: Armadillo exposure may be underreported in patients with HD because of fear of stigmatization and/or lack of access to care. CONCLUSIONS: Direct exposure to armadillos does not appear to be required for transmission of HD making a soil-mediated mechanism of indirect exposure plausible.

Epithelioid Fibrous Histiocytoma With Dot-Like Perinuclear ALK Expression and PRKAR2A-ALK Fusion.

Epithelioid fibrous histiocytoma (EFH) is a rare, benign, cutaneous neoplasm. This fibrohistiocytic tumor was once believed to be a variant of fibrous histiocytoma, but EFH is now known to be a distinct entity based on the presence of ALK gene rearrangements in most cases. The pattern of immunohistochemical expression of ALK in EFH in the literature thus far describes both granular cytoplasmic staining and nuclear staining. We present a case of EFH with dot-like Golgi pattern perinuclear ALK expression, a previously undescribed staining pattern. We surmised this unique staining pattern could be due to a novel fusion partner, and using FISH, we confirmed a rearrangement of the ALK (2p23) locus. Further investigation with whole transcriptome sequencing led to the discovery of PRKAR2A-ALK fusion, and the function of this fusion partner reflects a Golgi-predominant localization of the protein. Attention to the distinct immunohistochemical pattern of ALK expression may provide clues to the function of the fusion partner.

Comprehensive Review of Abdominopelvic Mesenchymal Tumors With Radiologic Pathologic Correlation and Update on Current Treatment Guidelines-Part 2.

Soft-tissue sarcomas are a diverse group of rare mesenchymal malignancies accounting for only 1% of all solid adult malignancies. These have been categorized in 12 broad groups by the World Health Organization (WHO) with their recent update in 2013. Majority of them lack specific imaging features serving as imaging conundrums for a radiologist. These are often large masses at presentation as they are asymptomatic or cause vague clinical symptoms. These tumors are challenging for surgeons as well as they find it difficult to achieve complete resection because of complex intra-abdominal anatomy and their close relationship with critical structures. Often, a multidisciplinary approach is required to decide on the most appropriate management for these complex cases so as to provide optimal patient care. Knowledge of the WHO classification, pathologic features, and treatment options available helps the radiologist make a meaningful contribution in multidisciplinary discussions of such cases and overall patient care. Liposarcoma (well-differentiated and dedifferentiated liposarcomas), leiomyosarcoma, and gastrointestinal stromal tumor are the 3 most common primary intra-abdominal sarcomas. In part 1 of this article, general features of soft-tissue sarcomas and some of the common tumors from WHO category 1-4 found in abdomen and pelvis are discussed. Part 2 will focus on common tumors from remainder of the WHO categories.