NR4A3 fluorescence in situ hybridization analysis in cytologic and surgical specimens of acinic cell carcinoma.

Acinic cell carcinoma (AciCC) may pose a diagnostic challenge, particularly on small biopsies and fine needle aspiration (FNA) because of its variable histology including potential high-grade transformation and its mimickers. Immunoreactivity with circumferential membranous staining for DOG1 can support the diagnosis of AciCC but is not entirely specific. A novel rearrangement t(4;9)(q13;q31) leading to up-regulation of nuclear receptor subfamily 4 group A member 3 (NR4A3) has been described in AciCC, is potentially detectable by fluorescence in situ hybridization (FISH) and may be useful in the evaluation for AciCC. Using NR4A3 Dual Color Break Apart Probe (ZytoVision, Germany) FISH was performed on AciCCs from 3 large academic institutions. NR4A3 rearrangement was defined as positive signal patterns in 15% of tissue interphase nuclei. Fifty-two AciCCs including 47 resections and 5 FNAs (including 5 paired FNA/resections) were analyzed. Five non-AciCC salivary gland tumors and 2 sialadenitis cases were used as controls. Eight AciCCs (15%; 8/52) failed FISH testing. FISH was positive in 23 AciCCs (sensitivity 59%, 23/39) with 100% concordance between 5 matched resection/FNAs (3 were positive for FISH and 2 were negative). FISH was negative in all non-AciCCs (specificity: 100%, 0/7). NR4A3 FISH has a sensitivity of 59% and specificity of 100% in detecting AciCC, which suggests that NR4A3 rearrangement-driven up-regulation is a recurrent, specific oncogenic event in AciCC, consistent with prior results. Hundred percent concordance between matched FNA/resection samples validates its potential utility on cytology samples.

Liver Histology in Septic Patients: Is It All About Ductular Cholestasis?

CONTEXT.­: Cholestasis within bile ductules is touted as a key histologic finding in septic patients but is not entirely sensitive or specific. The spectrum of other histopathologic findings in septic patients has not been thoroughly studied. OBJECTIVE.­: To evaluate histologic features in liver biopsies from septic patients, as well as mimics. DESIGN.­: For 121 liver samples where sepsis was mentioned in provided clinical information or in the pathologic differential diagnosis, we compiled patient outcome, clinical impression (sepsis or not), and blood culture results. We evaluated each case for inflammatory and cholestatic histologic findings, comparing them between patients with and without clinical sepsis, and between patients with gram-positive versus gram-negative results on blood culture. RESULTS.­: Cases from clinically septic patients (n = 77) showed portal mononuclear inflammation (52 cases, 68%), lobular neutrophilic inflammation (45, 58%), ductular reaction (58, 75%), lobular cholestasis (68, 88%), ductular cholestasis (52, 68%), and acidophil bodies (36, 47%). Findings between clinically septic and nonseptic patients were similar, though the latter more often had lobular mononuclear inflammation (19% versus 45%, P = .004). Ductular cholestasis rates were similar in both groups (68% versus 55%, P = .17). Ductular cholestasis had a sensitivity of 68%, a specificity of 45%, a positive predictive value of 68%, and an accuracy of 60% for the diagnosis of sepsis. Gram-positive and gram-negative sepsis caused comparable findings. CONCLUSIONS.­: Ductular cholestasis can be present in septic and nonseptic liver samples, though its presence does suggest the possibility of sepsis. Other common findings in sepsis include lobular cholestasis, ductular reaction, portal mononuclear inflammation, and lobular neutrophilic inflammation.

Intestinal Angiolipofibroma: Clinicopathologic Characteristics of 11 Cases.

Mesenchymal lesions of the gastrointestinal tract are generally uncommon compared with epithelial derived entities. Angiolipofibroma describes a rare gastrointestinal tract mesenchymal lesion composed of varied amounts of adipose tissue, fibrous tissue, along with admixed blood vessels. Descriptions of this entity are limited to few case reports describing a total of 5 lesions. Angiolipofibroma represents a benign entity that may uncommonly present as a mass lesion concerning for malignancy. The etiology is unclear; however, these may represent a reactive or hamartomatous process. In this article, we sought to further describe this entity and present an additional 11 cases.

Cecal Mucosal Myxoma: The First Report of a New Type of Mesenchymal Colon Polyp.

Myxomas are benign mesenchymal neoplasms of unknown etiology that most commonly occur in the cardiac atrium; however, other reported sites include the skin, joints, skeletal muscles, maxillofacial bones, and sinonasal tract. Myxomas involving the gastrointestinal (GI) tract are rare and are limited to a few published case reports. We are presenting, to our knowledge, the first case report of a mucosal myxoma in the colon presenting as a colonic polyp. A 49-year-old woman underwent a screening colonoscopy and was found to have a 0.2-cm sessile polyp in the cecum. Histologically, the polyp was composed of bland spindled cells in the lamina propria set in a hypocellular, myxoid stroma. The lesion was relatively well-demarcated from the surrounding mucosa. The overlying colonic epithelium showed no dysplasia. S-100 immunohistochemical stain showed only focal nonspecific positivity, while CD34, CD117, SMA, EMA, and desmin were all negative. Alcian blue special stain showed positive staining, supporting the diagnosis of myxoma. Myxomas in the GI tract are very rare, with this being the first reported case of a polypoid colonic mucosal myxoma. Previous reports of GI myxomas are limited to examples in the stomach, small bowel, and one recently reported case in the colon, all of which were submucosal lesions and not limited to the mucosa. In some of the prior reports, the patients had synchronous cardiac atrial myxomas. Mucosal colonic myxoma represents a newly identified mesenchymal polyp of the colon and pathologists should be aware of this diagnostic entity.

Heterotopic Respiratory Mucosa in the Rectum: An Unusual Type and Site of Heterotopia in the Gastrointestinal Tract.

Although pancreatic and gastric heterotopias are common findings in the gastrointestinal tract, heterotopic respiratory mucosa (HRM) in the rectum is extremely rare and has only been reported twice previously. We are presenting, to our knowledge, the third case of HRM in the rectum. A 56-year-old man with a history of chronic diarrhea presented for diagnostic colonoscopy, where he was found to have a rectal subepithelial nodule. He was subsequently referred to a tertiary medical center for further evaluation with rectal endoscopic ultrasound. Endoscopically, the nodule was hypoechoic, 2 to 3 mm in size, located in the submucosa, and did not appear to invade the muscularis propria. An uncomplicated endoscopic submucosal resection was subsequently performed. Microscopically, the nodule showed a multicystic complex lesion located in the submucosa, lined by ciliated pseudostratified columnar epithelium and surrounded by thin to moderately thick smooth muscle bundles and multiple lobules of seromucinous glands. There was associated acute and chronic inflammation. The rectum overlying the subepithelial lesion was lined by congested and edematous colonic mucosa and demonstrated no connection with the underlying cystic lesion. Immunohistochemical stains showed positive p63 basal cell staining in the respiratory epithelium of the lesion, while CDX2, TTF-1, and estrogen receptors were all negative. HRM is a benign nonneoplastic lesion with unclear etiology. Pathologists and gastroenterologists should be aware of this entity and consider it in their differential diagnosis for a subepithelial nodule in the rectum, keeping in mind that neoplastic processes can also develop in this location.

Continuous versus discontinuous tumor involvement: A dilemma in prostate biopsy quantitation.

BACKGROUND: No consensus has been reached for an optimal method of quantifying discontinuous tumor foci separated by intervening benign tissue on prostate biopsy (PBx). We examined sets of PBx, where cancer involved only one core, and corresponding radical prostatectomy (RP) specimens. METHODS AND RESULTS: Cases were divided into 3 groups-Group 1 (n = 80): <3 mm in end-to-end tumor measurement (continuous/discontinuous); Group 2 (n = 22): ≥3 mm in tumor length (continuous); and Group 3 (n = 15): ≥3 mm in end-to-end tumor measurement (discontinuous). The rate of Gleason score ≥7 was considerably lower in Group 1 (9%/30% on PBx/RP) than in Group 2 (50% [P < 0.001]/59% [P = 0.015] on PBx/RP) or Group 3 (40% [P = 0.005]/46% [P = 0.237] on PBx/RP). pT2 disease was significantly more often found in Group 1 (88%) than in Group 2 (68%, P = 0.049) or Group 3 (60%, P = 0.018). Surgical margin was significantly more often positive in Group 3 (27%) than in Group 1 (5%, P = 0.020), but not Group 2 (9%, P = 0.198). Moreover, estimated cancer volume (cc, mean ± SD) was significantly smaller in Group 1 (1.89 ± 1.98) than in Group 2 (3.56 ± 2.92, P = 0.026) or Group 3 (3.44 ± 2.02, P = 0.013). Kaplan-Meier analysis revealed higher risks of biochemical recurrence after RP in Group 2, compared with Group 1 (P = 0.001) or Group 3 (P = 0.096). In 93 patients with biopsy Gleason score 6 cancer, higher rates of pT2+/3 disease (P = 0.023) and positive margin (P = 0.026), as well as larger cancer volume (P = 0.063), on RP were still seen in Group 3, compared with Group 1, but their differences were not statistically significant between Group 2 and Group 3. CONCLUSIONS: Linear quantitation including intervening benign tissue on PBx may more precisely predict the actual tumor extent.

The Impact of Routine Frozen Section Assessment During Penectomy on Surgical Margin Status and Long-Term Oncologic Outcomes.

No recent studies have focused on assessing the role of intraoperative frozen section assessment (FSA) in the status of surgical margins (SMs) relating to the outcomes of penectomy cases. In this study, we investigated the utility of routine FSA of the SMs in men undergoing penectomy. A retrospective review identified consecutive patients who underwent partial (n = 26) or total (n = 12) penectomy for penile squamous cell carcinoma at our institution from 2004 to 2015. FSA of the SMs was performed in 21 (80.8%) partial and 10 (83.3%) total penectomies. FSAs were reported as positive (n = 3, 9.7%), atypical (n = 3, 9.7%), and negative (n = 25, 80.6%). All of the positive or negative FSA diagnoses were confirmed accurate on the frozen section controls, whereas the 3 cases with atypical FSA had non-malignant, atypical, and carcinoma cells, respectively, on the controls. Final SMs were positive in 6 (15.8%) penectomies, including 4 (12.9%) FSA cases versus 2 (28.6%) non-FSA cases (P = 0.569). Furthermore, initial positive (1 of 3) and atypical (3 of 3) FSA cases achieved negative conversion by excision of additional tissue sent for FSA. Kaplan-Meier analysis revealed that performing FSA or its number/diagnosis was not significantly associated with disease progression. Thus, performing FSA during penectomy does not appear to have any significant impact on final SM status nor long-term oncologic outcomes. However, as seen in at least 4 cases, select patients may benefit from the routine FSA.

Histologic mimics of malignant melanoma.

Although spongiotic (eczematous), psoriatic and cutaneous skin infections are among the most common in dermatology consultations, melanocytic lesions - including the different types of nevi and melanomas - are among those that cause a great deal of concern and stress to patients and their clinicians. A diagnosis of benign melanocytic nevus carries a very good prognosis. However, a diagnosis of melanoma might indicate more aggressive treatment, lifelong surveillance and a worse prognosis. Differentiating between these conditions is not always a straightforward process for clinicians and pathologists. Therefore, knowledge of melanoma mimickers is very important for clinicians in general, and dermatologists and pathologists in particular. In this review, we called attention to some of the more frequent benign but unusual melanocytic lesions that are of diagnostic concern for clinicians evaluating these cutaneous proliferations.