First description of a histopathologic grading system and relationship to outcomes after robotic median arcuate ligament release with celiac ganglionectomy and lymphadenectomy.

BACKGROUND: Two dominating theories regarding median arcuate ligament syndrome include vascular and neurogenic etiologies from celiac artery and ganglion compression, respectively. Celiac ganglionectomy is not routine during surgery, and specimens are rarely excised; therefore, the extent of nerve involvement and histopathology are unknown. Our study aims to characterize histopathologic findings in median arcuate ligament syndrome, establish a histopathologic grading system, and correlate with clinical outcomes. METHODS: Robotic median arcuate ligament release, celiac ganglionectomy, and lymphadenectomy were performed with specimens excised and stained using hematoxylin & eosin, trichrome, and S100. Neurofibrosis, adiposity, and reactive changes were described, a grading scale was developed, and results were analyzed with clinical outcomes. RESULTS: Fifty-four patients were evaluated, of whom 36 met inclusion criteria (81% female, 34.9 [25.9-47.5] years, body mass index 23.5 [19.6-28.1] kg/m2). Histopathologic evaluation revealed fibrosis (hematoxylin & eosin and trichrome median score 1.5 [0-2.5]), reactive lymphadenopathy (89%), intraparenchymal nerves (31%), and lipogranulomas (31%). Greater fibrosis was associated with a lack of preoperative celiac plexus block relief (100% vs. 30%, P = .044) and lower postoperative celiac artery velocities (198 vs 323 cm/s, P = .02). Intraparenchymal nerves were associated with greater decreases in pre to postoperative velocities (161 vs 84 cm/s, P = .037). Symptoms improved in 28 patients (78%). CONCLUSION: We developed the first histopathologic grading system and identified unique findings of intraparenchymal nerves and lipogranulomas. Histopathologic abnormalities were associated with objective improvement and symptomatic relief postoperatively. These findings support nerve compression and inflammation as predominant contributors to median arcuate ligament syndrome pain, celiac ganglia resection to treat symptoms, and continued histopathologic analysis to better elucidate median arcuate ligament syndrome etiology.

Colorectal Adenocarcinoma Derived From Mature Cystic Teratomas: A Case Report With Review of the Literature.

Mature cystic teratomas (MCTs) are the most common benign ovarian germ cell neoplasms in women of reproductive age. Rarely, somatic malignancies arise from MCTs, the most common being squamous cell carcinoma. Adenocarcinomas are less common and colorectal adenocarcinomas are extremely rare. We present a case of somatic adenocarcinoma of colorectal type which may pose challenges in diagnosis and treatment. A middle-aged female presented to the Emergency Department with lower abdominal pain. CT scan revealed an 11 cm sharply demarcated left pelvic mass. Laparoscopy showed a left ovarian mass with torsion, a smooth external surface, and thick brownish contents. An intraoperative evaluation was consistent with an adenocarcinoma. Permanent histopathology revealed adenocarcinoma of colorectal phenotype with necrosis. Additional evaluation of the cyst showed benign colonic epithelial lining. The immunohistochemistry (IHC) profile of positive CDX2 and CK20 and negative PAX8, CK7, ER, and PR suggested a colorectal-type somatic adenocarcinoma arising from the MCT and was staged as IA, after negative endoscopic findings. Due to their rarity and atypical symptoms, distinguishing metastatic tumors from MCT-derived somatic malignancies is a challenging process. CT scan and serum tumor markers can be helpful but are not definite. Thorough clinical evaluation and proper staging are necessary after pathologic evaluation. Extensive sampling and IHC can further characterize the origin of the tumor. Diligent sampling and a high index of suspicion in this case clinched the correct diagnosis and clinical management. The patient is being treated for stage IA ovarian cancer as opposed to stage IV metastatic colorectal cancer.

Clear Cell Renal Cell Carcinoma with Immunotherapy Effect Mimicking Xanthogranulomatous Pyelonephritis.

Renal cell carcinoma is now increasingly treated with checkpoint inhibitor therapy, predominantly in the metastatic setting or occasionally in the adjuvant setting; however, there is little published histopathology data demonstrating the post-therapy features of renal cell carcinoma tumor tissue. We report a middle-aged man, who was undergoing treatment with pembrolizumab for locally recurrent cutaneous basal cell carcinoma and was incidentally found to have a renal mass. Radical nephrectomy demonstrated a 5.0 cm renal mass with extensive xanthogranulomatous features, mimicking xanthogranulomatous pyelonephritis. However, rare clusters of cells demonstrated gland-like lumina, clear cytoplasm, and slightly increased atypia, suggesting scant residual renal cell carcinoma cells. Immunohistochemistry demonstrated focal positivity for pan-keratin and keratin 8/18, EMA, PAX8, CD10, and carbonic anhydrase 9 (CA9), supporting a diagnosis of renal cell carcinoma with extensive treatment response, to the point that it mimicked xanthogranulomatous pyelonephritis. This report demonstrates the histologic features of post-immunotherapy renal cell carcinoma, aiding pathologists in recognition of this phenomenon, which may be misdiagnosed as an inflammatory process, if immunotherapy was performed for other reasons.

Role of CD68 immunohistochemistry in categorizing benign nonmesothelial cell population and refining "atypical" category in serous fluid cytology.

BACKGROUND: Body fluids are rich in histiocytes and may mimic atypical epithelial cells morphologically. Histiocytes can pose a significant challenge in serous fluid cytology as they tend to appear atypical due to prolonged accumulation in serous fluids in vivo and processing by liquid-based cytology in vitro. Not many studies have documented the utilization of histiocytic marker such as CD68 in serous fluid cytology, which can subsequently reduce the "atypical" diagnostic category. METHODS: One thousand one hundred and twenty-nine cases of serous fluid cytology from 2016 to 2019 were reviewed and reclassified based on proposed classification of the international system for reporting serous fluid cytology. There were 133 cases with atypical diagnoses, out of which 51 cases had cellblocks. An immunohistochemistry (IHC) panel, including two mesothelial markers, two epithelial markers, and one histiocytic marker was applied to the atypical samples. Same IHC panel was utilized to evaluate 15 cases each from negative for malignancy (NFM), suspicious for malignancy (SFM), and malignant (MAL) categories for further comparison. RESULTS: After reevaluation of the cytology material with IHC stains, 924 (82%), 133 (12%), 23 (2%), and 49 (4%) of the cases were reclassified as NFM, atypia of uncertain significance, SFM, and MAL, respectively. Twenty-five out of 51 atypical cases (49%) were downgraded to "benign" after reevaluation with CD68 IHC. CONCLUSION: Histiocytes can mimic atypical epithelial cells in body fluids. Effective utilization of CD68 IHC will be beneficial in further refining the "atypical" diagnostic category in serous fluid cytology.

Pancreatic lymphoma: A cytologic diagnosis challenge.

Very rarely lymphoma primarily or secondarily involves the pancreas. Involvement of the pancreatic parenchyma with lymphoma clinically may mimic pancreatic ductal adenocarcinoma (PDA) and other mass-forming pancreatic lesions. Endoscopic ultrasound fine needle aspiration (EUS-FNA) is the first step in the diagnostic pathway of managing these patients by providing a cytology specimen. Cytologically, lymphoma of pancreas can be misdiagnosed for a wide variety of pancreatic neoplastic and non-neoplastic lesions. Cytological differential diagnosis includes well-differentiated adenocarcinoma, acinar cell carcinoma, well differentiated neuroendocrine tumor, and autoimmune pancreatitis. Gastroenterologist's skills in providing adequate sample for preparing smears, cell blocks and/or performing flow cytometry, and also cytopathologist's skills in detecting atypical lymphocytic population are crucial factors. Although cytology examination has limitations to subclassify lymphoma, it plays a key role to redirect clinicians into the right patient-care pathway. In this article, we present two cases of pancreatic lymphoma with emphasis on the discriminating cytomorphological features, and we also review literatures with reports of primary pancreatic lymphoma (PPL) to better understand the characteristics of this rare lesion.

APOL1 variants change C-terminal conformational dynamics and binding to SNARE protein VAMP8.

APOL1 variants in African populations mediate resistance to trypanosomal infection but increase risk for kidney diseases through unknown mechanisms. APOL1 is expressed in glomerular podocytes and does not vary with underlying kidney disease diagnoses or APOL1 genotypes, suggesting that the kidney disease-associated variants dysregulate its function rather than its localization or abundance. Structural homology searches identified vesicle-associated membrane protein 8 (VAMP8) as an APOL1 protein interactor. VAMP8 colocalizes with APOL1 in the podocyte, and the APOL1:VAMP8 interaction was confirmed biochemically and with surface plasmon resonance. APOL1 variants attenuate this interaction. Computational modeling of APOL1's 3-dimensional structure, followed by molecular dynamics simulations, revealed increased motion of the C-terminal domain of reference APOL1 compared with either variant, suggesting that the variants stabilize a closed or autoinhibited state that diminishes protein interactions with VAMP8. Changes in ellipticity with increasing urea concentrations, as assessed by circular dichroism spectroscopy, showed higher conformational stability of the C-terminal helix of the variants compared with the reference protein. These results suggest that reference APOL1 interacts with VAMP8-coated vesicles, a process attenuated by variant-induced reduction in local dynamics of the C-terminal. Disordered vesicular trafficking in the podocyte may cause injury and progressive chronic kidney diseases in susceptible African Americans subjects.

Concordant clear cell "mesonephric" carcinoma of the bladder and lung adenocarcinoma with clear cell features - multiple primaries versus metastatic neoplasms: a case report.

BACKGROUND: Clear cell carcinoma of the bladder is a rare variant of urinary bladder adenocarcinoma. We report a case of a patient with clear cell carcinoma of the bladder and a concordant right upper lobe pulmonary adenocarcinoma with clear cell features, and we address the role of immunohistochemistry and cytogenetic analysis in distinguishing the two primary malignancies. CASE PRESENTATION: Our patient was a 59-year-old African American woman who presented with hematuria. Her past medical history included invasive mammary carcinoma and end-stage renal disease treated with hemodialysis. A computed tomographic urogram revealed a 3-cm polypoid bladder mass. A follow-up chest computed tomographic scan revealed a 1-cm right upper lobe nodule. The patient underwent transurethral biopsy and subsequent radical cystectomy, as well as a transthoracic core needle biopsy of the lung nodule. Histologically, the bladder tumor consisted of flat, cuboidal to columnar cells with clear or eosinophilic cytoplasm and a hobnail appearance, organized in tubulocystic and papillary patterns. The neoplastic cells were diffusely positive for α-methylacyl-coenzyme A racemase, cancer antigen 125, and cytokeratin 7; focally positive for cytokeratin 20, P53, and carcinoembryonic antigen; and negative for thyroid transcription factor 1. The lung tumor demonstrated a glandular architecture with mucin production (positive for mucin with mucicarmine and periodic acid-Schiff with diastase stain). The neoplastic cells were diffusely positive for cytokeratin 7, napsin A, and thyroid transcription factor 1, and they were negative for cytokeratin 20 and cancer antigen 125. Genetic testing of the pulmonary neoplasm demonstrated ARID2 genomic alterations. CONCLUSIONS: The presence of clear cell features in both neoplasms raised the possibility of lung metastasis from the primary bladder tumor. However, the glandular architecture of the lung neoplasm along with its distinctive immunohistochemical and genetic profiles confirmed the presence of two separate primaries.

Assessment of the incidence of squamous cell papilloma of the esophagus and the presence of high-risk human papilloma virus.

BACKGROUND AND AIMS: There has been a recent increase in the incidence of oropharyngeal cancer (OPC) associated with high-risk human papilloma virus (HPV) infection. We investigated the incidence of esophageal papilloma and the presence of high-risk HPV infection. METHODS: This is a cross-sectional study conducted at a County teaching hospital. Patients with esophageal papilloma between January 2000 and December 2013 were identified. Patients with sufficient specimens were tested for the HPV virus. RESULTS: Sixty patients with esophageal papilloma lesions were identified from 2000 to 2013. (31 males, age 51 ± 13 years). The incidence was 0.13% in 2000 and increased to 0.57% in 2013 (P < 0.0001). Twenty-nine patients (48.3%) had a papilloma that was more than 5 mm in size, and 20% had multiple lesions. The papilloma was located in the distal esophagus in 35 (58.3%) patients, mid esophagus in 17 (28.3%) patients, and proximal in 8 (13.3%) patients. Three (5%) patients had associated OPC, and 9 (47.4%) of the 19 patients tested were positive for high-risk HPV serotype 16. CONCLUSIONS: The incidence of esophageal papilloma has increased by fourfolds over the past 14 years. About half of the tested patients demonstrated high risk HPV. This may suggest a potential growing risk for esophageal squamous cell cancer in the future.

Choriocarcinoma of the adrenal gland: A case report.

INTRODUCTION: Non-gestational, extragonadal choriocarcinoma is a rare clinical entity. PRESENTATION OF CASE: Herein, we report a 56 year old woman who presented with an incidental adrenal mass and was diagnosed with a non-gestational choriocarcinoma of the adrenal gland as the sole site of disease. DISCUSSION: To our knowledge, this is the first case of an ectopic primary adrenal choriocarcinoma. A metastasis from a primary tumor that completely regressed or that could not be identified is an alternate explanation. CONCLUSION: It should be recognized that choriocarcinoma can affect the adrenal gland and it should be considered as a rare cause for an adrenal incidentaloma.

APOL1 localization in normal kidney and nondiabetic kidney disease.

In patients of African ancestry, genetic variants in APOL1, which encodes apolipoprotein L1, associate with the nondiabetic kidney diseases, focal segmental glomerulosclerosis (FSGS), HIV-associated nephropathy (HIVAN), and hypertensive nephropathy. Understanding the renal localization of APOL1 may provide clues that will ultimately help elucidate the mechanisms by which APOL1 variants promote nephropathy. Here, we used immunohistology to examine APOL1 localization in normal human kidney sections and in biopsies demonstrating either FSGS (n = 8) or HIVAN (n = 2). Within normal glomeruli, APOL1 only localized to podocytes. Compared with normal glomeruli, fewer cells stained for APOL1 in FSGS and HIVAN glomeruli, even when expression of the podocyte markers GLEPP1 and synaptopodin appeared normal. APOL1 localized to proximal tubular epithelia in normal kidneys, FSGS, and HIVAN. We detected APOL1 in the arteriolar endothelium of normal and diseased kidney sections. Unexpectedly, in both FSGS and HIVAN but not normal kidneys, the media of medium artery and arterioles contained a subset of α-smooth muscle actin-positive cells that stained for APOL1. Comparing the renal distribution of APOL1 in nondiabetic kidney disease to normal kidney suggests that a previously unrecognized arteriopathy may contribute to disease pathogenesis in patients of African ancestry.

Cytologic detection of Strongyloides stercoralis in a 55-year-old Hispanic man with routine rectal/anal pap smear.

The anal-rectal cytology is introduced recently to evaluate human-papillomavirus related cellular changes in the cells of anal canal. It is especially useful in high risk patients such as HIV patients. Very few reports were published regarding cytomorphological findings in anal cytology. Strongyloides stercoralis is an enteric helminthic parasite with particular significance in immunocompromised patients. The infection is asymptomatic or manifests as mild gastrointestinal symptoms in normal hosts. The infection can be devastating in immunocompromised persons, and carries a high mortality rate. The presence of S. stercoralis larva in anal-rectal pap smears is rare. We report a case in a routine anal-rectal Pap smear with Strongyloides, and discuss the clinical significance and life cycle of S. stercoralis.

Primary melanoma of small intestine masquerading as gastrointestinal stromal tumor: a case report and literature review.

Malignant melanoma of the gastrointestinal tract is a rare entity among intestinal neoplasms. Primary intestinal melanoma is difficult to differentiate from metastatic melanoma, especially given that the primary cutaneous lesion has the potential to regress and disappear. In addition, melanoma by itself is a great mimicker of other neoplastic conditions and may create a major diagnostic challenge when presenting at an intra-abdominal location. Here we report a case of small intestinal melanoma in a 74-year-old female who presented with symptoms of intestinal bleeding and a preoperative clinical and radiological diagnosis of gastrointestinal stromal tumor. The initial frozen section diagnosis also favored gastrointestinal stromal tumor, however furthermore histological and immunohistochemical stain evaluation confirmed the diagnosis of intestinal melanoma.

Embolized crospovidone (poly[N-vinyl-2-pyrrolidone]) in the lungs of intravenous drug users.

Crospovidone is an insoluble polymer of N-vinyl-2-pyrrolidone that is used as a disintegrant in pharmaceutical tablets. It can potentially embolize to the lung when aqueous tablet suspensions are injected intravenously. In this report, we identified embolized crospovidone in autopsy-derived lung tissue from three adult IV drug users, 1 man and 2 women, whose ages respectively were 27, 38, and 40 years. Suspected crospovidone was compared with pharmaceutical-grade crospovidone by means of histochemical stains, transmission electron microscopy, and infrared spectroscopy. Similar particles were also observed by light microscopy in a 4-mg tablet of hydromorphone, a preparation prescribed to two of the patients. Two patients had sickle cell disease and were taking methadone and/or hydromorphone for pain management; the third was receiving parenteral hyperalimentation after small bowel resection. Crospovidone appeared as deeply basophilic, coral-like particles within pulmonary arteries and in extravascular foreign-body granulomas. Intrapulmonary crospovidone stained similarly to the pure substance, including intense staining with mucicarmine, Congo red, and Masson trichrome. With Movat pentachrome stain, both intravascular and purified crospovidone appeared orange-yellow, whereas most interstitial particles associated with giant cells stained blue-green. Alcian blue failed to stain intravascular or purified crospovidone but strongly decorated some phagocytized particles. Ultrastructurally, both purified powder and tissue deposits of crospovidone appeared as irregular, electron dense, laminated, and finely granular material. Intrapulmonary crospovidone was associated with inflammatory cells and exhibited degenerative changes. By infrared spectroscopy, crospovidone in tissue had the same spectral characteristics as pharmaceutical grade crospovidone and the library reference, polyvinylpyrrolidone (PVP). We conclude that crospovidone contributes to pulmonary vascular injury in some persons who illicitly inject pharmaceutical tablets. It is readily identifiable histologically and distinguishable from other tablet constituents, such as cornstarch, talc, and microcrystalline cellulose. The variable staining with Alcian blue and Movat suggests that crospovidone is altered in vivo by the inflammatory response.