Primary cutaneous apocrine carcinoma, arising in tubular apocrine adenoma.

Primary cutaneous apocrine carcinoma is a rare adnexal tumor that arises from apocrine progenitor cells. These tumors may be associated with benign apocrine hyperplasia, and a longstanding history of a lesion should not preclude a malignant diagnosis. We report a case of a 70-year-old female who presented to the clinic with a 3-year history of an asymptomatic vulvar lesion. An excisional biopsy was performed. Histopathologic examination revealed a tumor with two distinct components. The first component was determined to be a benign tubular apocrine adenoma. The second component, arising within the apocrine adenoma, was determined to be an apocrine carcinoma based on histopathologic features and immunohistochemical profile. Twelve months after subsequent wide local excision and sentinel node biopsy, the patient is alive without recurrence.

Lower Extremity Nodules After Spelunking in Mexico.

Mycobacterium marinum is a non-tuberculous mycobacterium that presents as a nodular granulomatous disease. The bacillus can infect humans when broken skin is exposed to a contaminated aquatic environment. M. marinum infections are usually isolated to the skin and soft tissues and can spread in a lymphatic distribution. A 26-year-old male cut his right ankle while spelunking in Tulum, Mexico. He presented to his primary care physician three months after he sustained the laceration with a nonhealing wound on the right lateral posterior ankle. Examination of the lesion demonstrated erythematous, violaceous, and hyperpigmented indurated plaques with satellite lesions noted at the right medial, posterior, and lateral ankle. The lesion characteristics raised initial suspicion for an invasive fungal infection. Biopsy of the lesion demonstrated epidermal ulceration covered by neutrophilic serum, marked underlying dermal acute inflammation, and granulation tissue. A mild perivascular, predominantly lymphocytic infiltrate was present in the deep dermis with no evidence of granuloma. Acid-fast bacilli culture plated onto chocolate agar confirmed the species M. marinum.

Sarcoidosis of the Bile Duct.

Sarcoidosis is an inflammatory disease that affects multiple organs. The lungs are the most commonly involved organs. Although a large proportion of patients with sarcoidosis have liver involvement, bile duct involvement is rare. Here, we present a case of a 56-year-old African American patient presented with painless jaundice because of extrahepatic bile duct sarcoidosis. Our diagnostic approach using endoscopic cholangioscopy with targeted biopsies confirmed the diagnosis. Multiple bile duct stent exchanges were performed to manage the bile duct stricture in addition to medical therapy.

Metastatic head and neck cutaneous basal cell carcinomas: a retrospective observational study.

Cutaneous basal cell carcinoma is usually an indolent and slow-growing tumor with potential for local invasion and recurrence; however, metastatic events are exceedingly rare. The annual incidence of metastasis is estimated to range between 0.00281 and 0.05%. A retrospective search in the pathology database of a single tertiary institution was performed in the period between 1999 to 2019. Primary cutaneous metastatic basal cell carcinomas had paraffin blocks and glass slides retrieved. A total of 8673 cases was identified. The overall prevalence of metastatic tumors was 0.05% (4/8673). The median patient's age at diagnosis was 61 years old (range 52-79). The most common primary site of tumor was nose (2/4) and the most common histological subtype was infiltrative. The sampled lymph nodes were identified during primary tumor resection, except for 1 patient who had a sentinel lymph node biopsy performed as a surgeon individual decision. One patient had hematogenous spread to the pleura, diagnosed 5 years after diagnosis. In summary, this study adds new data to the current literature in metastatic primary cutaneous basal cell carcinomas and highlights the importance of early diagnosis and appropriate surgical excision in an effort to prevent local advanced disease, recurrence and lymphovascular dissemination.

Development and Validation of a Deep Learning Model to Quantify Interstitial Fibrosis and Tubular Atrophy From Kidney Ultrasonography Images.

Importance: Interstitial fibrosis and tubular atrophy (IFTA) is a strong indicator of decline in kidney function and is measured using histopathological assessment of kidney biopsy core. At present, a noninvasive test to assess IFTA is not available. Objective: To develop and validate a deep learning (DL) algorithm to quantify IFTA from kidney ultrasonography images. Design, Setting, and Participants: This was a single-center diagnostic study of consecutive patients who underwent native kidney biopsy at John H. Stroger Jr. Hospital of Cook County, Chicago, Illinois, between January 1, 2014, and December 31, 2018. A DL algorithm was trained, validated, and tested to classify IFTA from kidney ultrasonography images. Of 6135 Crimmins-filtered ultrasonography images, 5523 were used for training (5122 images) and validation (401 images), and 612 were used to test the accuracy of the DL system. Kidney segmentation was performed using the UNet architecture, and classification was performed using a convolution neural network-based feature extractor and extreme gradient boosting. IFTA scored by a nephropathologist on trichrome stained kidney biopsy slide was used as the reference standard. IFTA was divided into 4 grades (grade 1, 0%-24%; grade 2, 25%-49%; grade 3, 50%-74%; and grade 4, 75%-100%). Data analysis was performed from December 2019 to May 2020. Main Outcomes and Measures: Prediction of IFTA grade was measured using the metrics precision, recall, accuracy, and F1 score. Results: This study included 352 patients (mean [SD] age 47.43 [14.37] years), of whom 193 (54.82%) were women. There were 159 patients with IFTA grade 1 (2701 ultrasonography images), 74 patients with IFTA grade 2 (1239 ultrasonography images), 41 patients with IFTA grade 3 (701 ultrasonography images), and 78 patients with IFTA grade 4 (1494 ultrasonography images). Kidney ultrasonography images were segmented with 91% accuracy. In the independent test set, the point estimates for performance matrices showed precision of 0.8927 (95% CI, 0.8682-0.9172), recall of 0.8037 (95% CI, 0.7722-0.8352), accuracy of 0.8675 (95% CI, 0.8406-0.8944), and an F1 score of 0.8389 (95% CI, 0.8098-0.8680) at the image level. Corresponding estimates at the patient level were precision of 0.9003 (95% CI, 0.8644-0.9362), recall of 0.8421 (95% CI, 0.7984-0.8858), accuracy of 0.8955 (95% CI, 0.8589-0.9321), and an F1 score of 0.8639 (95% CI, 0.8228-0.9049). Accuracy at the patient level was highest for IFTA grade 1 and IFTA grade 4. The accuracy (approximately 90%) remained high irrespective of the timing of ultrasonography studies and the biopsy diagnosis. The predictive performance of the DL system did not show significant improvement when combined with baseline clinical characteristics. Conclusions and Relevance: These findings suggest that a DL algorithm can accurately and independently predict IFTA from kidney ultrasonography images.

Superparamagnetic iron oxide nanoparticles of curcumin enhance gemcitabine therapeutic response in pancreatic cancer.

Pancreatic cancer is a complex disease accounting for fibrotic tumors and an aggressive phenotype. Gemcitabine (GEM) is used as a standard therapy, which develops chemoresistance leading to poor patient outcome. We have recently developed a superparamagnetic iron oxide nanoparticle (SPION) formulation of curcumin (SP-CUR), which is a nontoxic, bioactive anti-inflammatory/anti-cancer agent for its enhanced delivery in tumors. In this study, we demonstrate that SP-CUR effectively delivers bioactive curcumin to pancreatic tumors, simultaneously enhances GEM uptake and its efficacy. Mechanistic revelations suggest that SP-CUR targets tumor microenvironment via suppression of sonic hedgehog (SHH) pathway and an oncogenic CXCR4/CXCL12 signaling axis that inhibits bidirectional tumor-stromal cells interaction. Increased GEM uptake was observed due to upregulation of the human nucleoside transporter genes (DCK, hCNT) and blocking ribonucleotide reductase subunits (RRM1/RRM2). Additionally, co-treatment of SP-CUR and GEM targets cancer stem cells by regulating pluripotency maintaining stemness factors (Nanog, Sox2, c-Myc and Oct-4), and restricting tumor sphere formation. In an orthotopic mouse model, an enhanced accumulation of SP-CUR was found in pancreas, which potentiated GEM to reduce tumor growth and metastasis. Analysis of tumor tissues suggest that the treatment inhibits tumor stroma (α-SMA, Desmin and Hyluronic Acid) and induces changes in cell stiffness, as measured via Atomic Force Microscopy. This was accompanied by alteration of key cellular proteins of SHH signaling such as SHH, Gli-1, Gli-2, Sufu, and NFĸB-65 as indicated by Immunoblotting and Immunohistochemistry. These results suggest that SP-CUR has a great potential for future clinical use in the management of pancreatic cancer.