Interstitial mycosis fungoides: A rare presentation of mycosis fungoides with overlapping granulomatous and folliculotropic features.

BACKGROUND: Interstitial mycosis fungoides (IMF) is a rare subtype of mycosis fungoides (MF) characterized by atypical lymphocytes infiltrating the reticular dermis between collagen bundles with limited epidermotropism and variable granulomatous features. METHODS: Retrospective single institution review of 31 cases of IMF including clinical characteristics, disease course and pathological features. RESULTS: Our cohort was predominately male (19; 61%, M:F 1.6:1) with a mean age at diagnosis of 43 years (range 11-85), mean signs/symptoms duration of 7 years prior to diagnosis, and 6 years mean follow-up duration. Clinically, patients often exhibited symmetric ill-defined patches/plaques involving intertriginous regions with tan-yellow hyperpigmentation and follicular-based papules, wrinkling, and alopecia. Lymphadenopathy was noted in seven patients. Fifteen (52%) patients were in near or complete clinical remission at the latest follow-up. T-cell receptor gene rearrangement was positive in 23/24 (96%) cases. Histopathologically, atypical cells were small-medium, CD4+ (29; 94%) or rarely CD4+/CD8+ (1; 3%) lymphocytes infiltrating the reticular dermis with thickened collagen bundles (27; 87%), multinucleated giant cells (12; 39%), and often tracing along adnexa with subtle folliculotropism (12/20; 60%). CONCLUSIONS: Our study demonstrates IMF is an indolent subtype of MF with distinct features, including frequent granulomatous and subtle follicular involvement resulting in alopecia.

Mortality and Autopsy Findings in Patients with Pyoderma Gangrenosum: A Multi-Institutional Series.

INTRODUCTION: Pyoderma gangrenosum (PG) is a rare ulcerative skin condition with an increased risk of mortality compared to the general population. The causes of this increased risk are not well understood. Misdiagnosis is common in PG, and many studies are limited by the inclusion of misdiagnosed cases. The goal of this study was to review autopsy findings, identify causes of death, and identify factors that may worsen outcomes among deceased patients confirmed to have PG. METHODS: Data was retrospectively reviewed from the electronic medical records at five academic hospitals. A search was conducted for deceased patients with a diagnosis of PG who had an autopsy performed between 2010 and 2020. We report a descriptive analysis of 11 patients and their clinical characteristics, causes of death, and autopsy findings. RESULTS: The average age of death was 62.9 years. Seven patients had at least one underlying condition known to be associated with PG including inflammatory bowel disease, inflammatory arthritis, or a hematologic disorder. The most common cause of death was infection (n = 6, 54.5%), followed by pulmonary embolism (n = 3, 27.3%), and myelodysplastic syndrome (n = 2, 18.2%). Six patients (54.5%) were taking systemic steroids at the time of death. CONCLUSION: The development of PG may shorten life expectancy among those with underlying conditions associated with PG, and common treatments for PG may contribute to the risk of fatal complications. Awareness of the risk of infection, thrombosis, and malignancy among those with PG is necessary for proper management. Further research is needed to explore the relationship between PG and thromboembolism.

Limb amputation in patients with pyoderma gangrenosum: a multi-institutional case series.

INTRODUCTION: Pyoderma gangrenosum (PG) can represent a diagnostic challenge, leading to missed or delayed diagnosis. With prolonged immunosuppressive therapy, the risk of infections is elevated, predisposing patients to receive anti-infective treatments and, in serious cases, amputations. Limb amputations have been reported as complication of PG misdiagnosis but can also occur as a complication of long-standing PG ulcers. METHODS: We aimed to describe the clinical characteristics of patients with PG leading to limb amputation through a multicenter retrospective case series between 2010 and 2020 including patients with PG who underwent limb amputation. We report a descriptive analysis of these patients' clinical course and outcome. RESULTS: Ten patients with PG who underwent at least one limb amputation were identified. Six were male (60%). Mean age was 65 years. All patients had ulcerative PG on the lower extremities, with a mean PG ulcer duration of 30.6 months. Six patients had PG-related comorbidities such as ulcerative colitis, myelodysplasia, and inflammatory arthritis. Other significant comorbidities included diabetes mellitus (DM) (five patients), coronary artery disease (five patients), and chronic kidney disease (two patients). The majority of patients (8/10) were correctly diagnosed with PG prior to amputation, whereas two patients were misdiagnosed with necrotizing soft tissue infections (NSTIs). All patients received intravenous antibiotics without substantial improvement. Eight patients developed sepsis and shock-like symptoms and the diagnosis of NSTIs was considered. Below-knee amputation was performed in six patients and above-knee amputation in four. Four patients had amputation performed twice because of recurrent NSTIs. Conclusion This multicenter case series sheds light on practice gaps for physician assessing patients with PG, in that limb amputation may result from PG misdiagnosis or complications thereof. Elderly patients (above 65 years) with coexisting lower extremity PG, DM, and/or chronic cardiac or renal disease should be managed with particular care toward preventing infection/NSTIs to prevent further complications such as limb amputations.

A novel GAB2::BRAF fusion in cutaneous non-Langerhans-cell histiocytosis with systemic involvement.

Several mutations and gene fusions involved in the mitogen-activated protein kinase (MAPK) pathway have been reported in histiocytic neoplasms including Langerhans cell histiocytosis and non-Langerhans-cell histiocytosis (NLCH). We identified a GAB2::BRAF fusion in a cutaneous lesion from a 22-year-old woman who presented with central diabetes insipidus and red/brown papules on her face, oral mucosa, axilla, and groin. Skin biopsy showed a CD68+, S100-, and CD1a- histiocytic proliferation consistent with NLCH, best clinically classified as xanthoma disseminatum. Next-generation sequencing identified a GAB2::BRAF fusion involving exon 2 of GAB and exon 10 of BRAF. This case implicates a novel fusion in the MAPK signaling pathway, not previously reported in histiocytic neoplasms, as a possible driver of NLCH. Our findings underscore the utility of performing molecular studies on skin biopsy specimens with NLCH to help identify potential targets for therapy.

Role of DNA Flow Cytometry in the Diagnosis of Malignancy in Bile Duct Biopsies Using Paraffin-Embedded Tissue.

OBJECTIVES: Histopathologic evaluation of bile biopsies for biliary strictures is frequently challenging and is affected by interobserver disagreement. Reliable ancillary tests that can help differentiate benign from malignant are not available. This study aimed to evaluate whether DNA content abnormalities detected by flow cytometry on formalin-fixed, paraffin-embedded (FFPE) tissue can help differentiate benign/reactive, dysplastic from malignant cell populations in bile duct biopsies. METHODS: We performed DNA flow cytometry on 30 FFPE bile duct biopsies in 5 well-defined diagnostic categories: (1) negative for dysplasia (NED), (2) low-grade dysplasia (LGD), (3) high-grade dysplasia (HGD), (4) carcinoma (CA), and (5) indefinite for dysplasia (IND). RESULTS: Abnormal DNA content was detected in 0 NED, 5 LGD (62.5%), 2 HGD (33.3%), 3 CA (60%), and 4 IND (80%) samples. As a diagnostic marker, the estimated sensitivity, specificity, positive predictive value, and negative predictive value were 63%, 100%, 100%, and 50%, respectively, for diagnosing HGD or CA. CONCLUSIONS: DNA flow cytometry analysis is a useful ancillary test for the interpretation of bile duct biopsies. DNA content abnormalities, when correlated with histologic findings, will not only help confirm the morphologic impression but also identify patients who are at a higher risk of developing malignancy.

Utility of abdominal skin punch biopsy for detecting systemic amyloidosis.

BACKGROUND: Early and accurate diagnosis of systemic amyloidosis (SA) is critical for optimal patient outcomes. Biopsy of clinically uninvolved skin and subcutaneous tissue including abdominal skin punch biopsy (ASPB) is often used as a surrogate for affected organ sampling. There is a lack of published data on the sensitivity and specificity of ASPB for diagnosing SA. METHODS: Retrospective chart review between 2000 and 2020 of all ASPB was performed to diagnose SA. Amyloid deposition was confirmed by Congo red stain. Study group includes patients with histopathologically and clinically confirmed diagnosis of SA. Control group includes patients without histopathology of amyloid deposition and no clinical SA. RESULTS: Forty-one patients meeting inclusion criteria were analyzed; 23 study group and 18 control group patients. The overall diagnostic sensitivity of ASPB was 43% (95% CI 23%-66%) and the specificity 100% (95% CI 81%-100%). The AL amyloidosis diagnostic sensitivity was 64% (95% CI 35%-87%). ASPB >10 mm in depth had 100% (95% CI 54%-100%) sensitivity compared to 24% for depth ≤10 mm (P = .002). CONCLUSIONS: ASPB is a minimally invasive and highly specific method of diagnosing SA. It is particularly sensitive for diagnosing AL amyloidosis and the diagnostic sensitivity can be significantly improved with adequate biopsy depth and diameter.

Hepatic artery aneurysm in the setting of focal nodular hyperplasia.

Hepatic artery aneurysms (HAA) are rare and may be seen in the setting of infection and vascular disease. Clinical presentation is variable but many are found incidentally during imaging studies. The association of HAA with focal nodular hyperplasia (FNH) is rarely reported in literature. We present the case of a 68-year-old woman found to have a hepatic artery aneurysm and hepatic mass, both within the same liver segment. FNH and hepatic adenomas share similar imaging features but have different treatments due to malignant potential of the latter, and biopsy should be performed when adenoma cannot be excluded. In this case biopsy of the mass revealed it to be FNH and the aneurysm was treated with embolization rather than surgery.

Loss of the virulence plasmid by Shigella sonnei promotes its interactions with CD207 and CD209 receptors.

Introduction. Shigella sonnei, the cause of bacillary dysentery, belongs to Gram-negative enteropathogenic bacteria. S. sonnei contains a 210 kb virulence plasmid that encodes an O-antigen gene cluster of LPSs. However, this virulence plasmid is frequently lost during replication. It is well-documented that after losing the O-antigen and becoming rough strains, the Gram-negative bacteria may express an LPS core on its surface. Previous studies have suggested that by using the LPS core, Gram-negative bacteria can interact with several C-type lectin receptors that are expressed on antigen-presenting cells (APCs).Hypothesis/Gap Statement. S. sonnei by losing the virulence plasmid may hijack APCs via the interactions of LPS-CD209/CD207.Aim. This study aimed to investigate if the S. sonnei rough strain, by losing the virulence plasmid, interacted with APCs that express C-type lectins of human CD207, human CD209a and mouse CD209b.Methodology. SDS-PAGE silver staining was used to examine the O-antigen expression of S. sonnei WT and its rough strain. Invasion assays and inhibition assays were used to examine the ability of S. sonnei WT and its rough strain to invade APCs and investigate whether CD209 and CD207 are receptors for phagocytosis of rough S. sonnei. Animal assays were used to observe the dissemination of S. sonnei.Results. S. sonnei did not express O-antigens after losing the virulence plasmid. The S. sonnei rough strain invades with APCs, including human dendritic cells (DCs) and mouse macrophages. CD209 and CD207 are receptors for phagocytosis of rough S. sonnei. Expression of the O-antigen reduces the ability of the S. sonnei rough strain to be disseminated to mesenteric lymph nodes and spleens.Conclusion. This work demonstrated that S. sonnei rough strains - by losing the virulence plasmid - invaded APCs through interactions with CD209 and CD207 receptors.

Murine SIGNR1 (CD209b) Contributes to the Clearance of Uropathogenic Escherichia coli During Urinary Tract Infections.

Uropathogenic Escherichia coli (UPEC), a Gram-negative bacterial pathogen, is a major causative agent of urinary tract infections (UTIs). However, the molecular mechanisms of how UPEC causes infections have not been determined. Recent studies indicated that certain enteric Gram-negative bacteria interact with and hijack innate immune receptors DC-SIGN (CD209a) and SIGNR1 (CD209b), often expressed by antigen-presenting cells (APCs), such as macrophages, leading to dissemination and infection. It was not known whether UPEC could utilize DC-SIGN receptors to promote its infection and dissemination similarly to the enteric pathogens. The results of this study reveal that UPEC interacts with CD209-expressing macrophages and transfectants. This interaction is inhibited by anti-CD209 antibody, indicating that CD209s are receptors for UPEC. Additionally, in contrast to the results of previous studies, mice lacking SIGNR1 are more susceptible to infection of this uropathogen, leading to prolonged bacterial persistence. Overall, the results of our study indicate that the innate immune receptor CD209s participate in the clearance of UPEC during UTIs.

Gender Disparity in Leadership Positions of General Surgical Societies in North America, Europe, and Oceania.

Background  Despite the number of female medical-school applicants reaching an all-time high and the increasing number of females in surgical training, males retain an overwhelming majority in senior surgical academic positions and formal leadership positions. This study aims to better understand the extent of and influences for gender disparity in general surgical societies throughout North America, Europe, and Oceania.  Methods  Data collection for this retrospective cross-sectional study took place between June and December 2017. Committee and subcommittee members from the eight selected general surgical societies that met the inclusion criteria (n = 311) were compiled into an Excel spreadsheet in which the data was recorded. Analyzed metrics included university academic ranking, surgical society leadership position, h-index, number of citations, and total publications. SCOPUS database (Elsevier, Amsterdam, Netherlands) was used to generate author metrics, and STATA version 14.0 (StataCorp, College Station, TX) was used for statistical analysis. Results Overall, 83.28% of members of the entities we studied were male and 16.72% were females. Males had significantly higher representation than females in all societies (Pearson chi2 = 29.081; p-value = 0.010). Females were underrepresented in all society leadership positions and university academic rankings. Male members had a higher median h-index, more number of citations, and more total publications. Conclusions The composition of the general surgical societies included in this study demonstrated significant gender disparity. Female inclusivity initiatives and policies must be initiated to promote greater research productivity and early career opportunities for female surgeons in the specialty of general surgery.