BRAF V600E immunohistochemistry as a useful tool in the diagnosis of melanomas with ambiguous morphologies and immunophenotypes.

We report three melanoma cases in which BRAF V600E immunohistochemistry (IHC) was valuable for diagnosis. Patient 1: In a patient with a history of primary melanoma on the chest and metastatic melanoma to right breast after undergoing multiple local and systemic therapies, a lung metastasis exhibited chondroid differentiation, aberrant myofibroblastic marker expression, and rare pancytokeratin positivity, without melanocytic marker expression. Patient 2: After targeted and immunotherapy for primary melanoma on the scalp as well as regional and distant metastatic melanoma, an omental metastasis showed CDX2-positive glandular structures that were negative for melanocytic markers. It was initially misdiagnosed as primary gastrointestinal adenocarcinoma. Patient 3: A patient with history of melanoma showing epithelioid morphology on the right thigh presented with multiple soft tissue nodules on skin, lymph nodes and internal organs after being lost to follow-up for 4 years. A biopsy specimen from the right thigh showed spindled cells with scattered pancytokeratin cocktail positivity and ambiguous staining for melanocytic markers. For melanomas with ambiguous morphologies and/or immunophenotypes in each of the three patients, BRAF V600E expression by IHC was maintained in both primary and metastatic melanoma specimens examined. These cases highlight the utility of BRAF V600E IHC in the diagnosis of melanoma.

Recovery rate of adrenal function after surgery in patients with acromegaly is higher than in those with non-functioning pituitary tumors: a large single center study.

PURPOSE: To compare hypothalamus-pituitary-adrenal (HPA) axis integrity at diagnosis and recovery after transsphenoidal surgery (TSS), in acromegaly patients, compared with tumor size matched non-functioning adenoma (NFA) patients. METHODS: A retrospective 7-year evaluation of acromegaly patients, who underwent TSS with 52 weeks follow-up at a single institution, was undertaken. 50 acromegaly with complete follow-up data at all points and 50 NFA patients were matched for tumor size; HPA axis was similarly assessed pre-operatively and at 6, 12 and 52 weeks post-operatively. Recovery of HPA axis and gender specific prevalence of adrenal insufficiency (AI), were analyzed in both groups. We also studied AI in acromegaly patients requiring medical therapy post-operatively vs those in remission after surgery. RESULTS: AI remained less prevalent in acromegaly vs NFA (acromegaly, p = 0.01; NFA, p = 0.15) at 52 weeks after surgery, although the prevalence of AI decreased in both groups from baseline by 52 weeks. Additionally, recovery from baseline AI was significantly greater by 52 weeks in acromegaly patients over NFA patients (p = 0.001). Recovery of HPA axis in acromegaly patients remained significant (p = 0.03) despite the need for medical therapy. AI at baseline was proportionately more prevalent in acromegalic males at baseline (p = 0.002) but no gender difference was apparent at 52 weeks (p = 0.35). Conversely, in NFA patients, no gender difference was apparent pre-operatively (p = 0.49), but AI was more prevalent in males at 52 weeks (p = 0.001). CONCLUSION: In the longest comparative study to date using a standard assessment modality, HPA axis recovery was more frequent in acromegaly compared to NFA patients, independent of tumor size, cavernous sinus invasion (CSI), and body mass index (BMI). HPA axis integrity must be carefully and periodically monitored in acromegaly patients during short- and long-term follow-up to prevent overtreatment with glucocorticoids.

Remission rate after transsphenoidal surgery in patients with pathologically confirmed Cushing's disease, the role of cortisol, ACTH assessment and immediate reoperation: a large single center experience.

Postoperative serum cortisol is used as an indicator of Cushing's disease (CD) remission following transsphenoidal surgery (TSS) and guides (controversially) the need for immediate adjuvant treatment for CD. We investigated postoperative cortisol and adrenocorticotropic hormone (ACTH) levels as predictors of remission/recurrence in CD in a large retrospective cohort of patients with pathologically confirmed CD, over 6 years at a single institution. Midnight and morning cortisol, and ACTH at 24-48 h postoperatively (>24 h after last hydrocortisone dose) were measured. Remission was defined as normal 24-h urine free cortisol, normal midnight salivary cortisol, a normal dexamethasone-corticotropin releasing hormone (CRH) test or continued need for hydrocortisone, assessed periodically. Statistical analysis was performed using PASW 18. Follow up data was available for 52 patients (38 females and 14 males), median follow up was 16.5 month (range 2-143 months), median age was 45 years (range 21-72 years), 28 tumors were microadenomas and 16 were macroadenomas, and in eight cases no tumor was observed on magnetic resonance imaging. No patient with postoperative cortisol levels >10 mcg/dl were found to be in remission. Ten of the 52 patients with cortisol >10 mcg/dl by postoperative day 1-2 underwent a second TSS within 7 days. Forty-three patients (82.7%) achieved CD remission (36 after one TSS and 7 after a second early TSS) and six patients suffered disease recurrence (mean 39.2 ± 52.4 months). An immediate second TSS induced additional hormonal deficiencies (diabetes insipidus) in three patients with no surgical complications. Persistent disease was noted in nine patients despite three patients having an immediate second TSS. Positive predictive value for remission of cortisol <2 mcg/dl and ACTH <5 pg/ml was 100%. Cortisol and ACTH levels (at all postoperative time points and at 2 months) were correlated (r = 0.37, P < 0.001). Nadir serum cortisol of ≤2 mcg/dl and ACTH <5 pg/ml predicted remission (P < 0.005), but no level predicted lack of recurrence. Immediate postoperative ACTH/cortisol did not predict length of remission. No patients with postoperative cortisol >10 mcg/dl were observed to have delayed remission; all required additional treatment. There was no significant difference in age, body mass index, tumor size and length of follow-up between postoperative cortisol groups: cortisol ≤2 mcg/dl, cortisol >5 mcg/dl and cortisol >10 mcg/dl. Immediate postoperative cortisol levels should routinely be obtained in CD patients post TSS, until better tools to identify early remission are available. Immediate repeat TSS could be beneficial in patients with cortisol >10 mcg/dl and positive CD pathology: our combined (micro- and macroadenomas) remission rate with this approach was 82.7%. ACTH measurements correlate well with cortisol. However, because no single cortisol or ACTH cutoff value excludes all recurrences, patients require long-term clinical and biochemical follow-up. Further research is needed in this area.

Juvenile granulosa cell tumor in a transgender male with Ollier disease: A case report.

•Multiple case reports are published on patients with Ollier's disease presenting simultaneously with granulosa cell tumors.•More medical conditions are being treated with androgens and estrogens, including gender dysphoria.•Caution should be given to transgender patients on active hormonal therapy.•Providers should consider prescreening for hormonally responsive medical conditions.

Utility of Whole Slide Imaging for Intraoperative Consultation: Experience of a Large Academic Center.

CONTEXT.­: In the United States, review of digital whole slide images (WSIs) using specific systems is approved for primary diagnosis but has not been implemented for intraoperative consultation. OBJECTIVE.­: To evaluate the safety of review of WSIs and compare the efficiency of review of WSIs and glass slides (GSs) for intraoperative consultation. DESIGN.­: Ninety-one cases previously submitted for frozen section evaluation were randomly selected from 8 different anatomic pathology subspecialties. GSs from these cases were scanned on a Leica Aperio AT2 scanner at ×20 magnification (0.25 µm/pixel). The slides were deidentified, and a short relevant clinical history was provided for each slide. Nine board-certified general pathologists who do not routinely establish primary diagnoses using WSIs reviewed the WSIs using Leica Aperio ImageScope viewing software. After a washout period of 2-3 weeks, the pathologists reviewed the corresponding GSs using a light microscope (Olympus BX43). The pathologists recorded the diagnosis and time to reach the diagnosis. Intraobserver concordance, time to diagnosis, and specificity and sensitivity compared to the original diagnosis were evaluated. RESULTS.­: The rate of intraobserver concordance between GS results and WSI results was 93.7%. Mean time to diagnosis was 1.25 minutes for GSs and 1.76 minutes for WSIs (P < .001). Specificity was 91% for GSs and 90% for WSIs; sensitivity was 92% for GSs and 92% for WSIs. CONCLUSIONS.­: Time to diagnosis was longer with WSIs than with GSs, and scanning GSs and uploading the data to whole slide imaging systems takes time. However, review of WSIs appears to be a safe alternative to review of GSs. Use of WSIs allows reporting from a remote site during a public health emergency such as the COVID-19 pandemic and facilitates subspecialty histopathology services.

Malignant Peritoneal Mesothelioma in the setting of a Ventriculo-Peritoneal Shunt: A novel clinical presentation.

We report a case of malignant peritoneal mesothelioma (MPM) in a 31-year-old male with history of cerebral palsy, hydrocephalus, and ventriculoperitoneal shunt (VPS) placed since infancy. He presented with fever, abdominal pain and distension. Computed tomography scan revealed a thick-walled rim-enhancing fluid collection, interpreted as pseudocyst. Intraoperatively, diffuse nodular peritoneal thickening with adhesions was demonstrated. The resection specimen consisted of multiple membranous fragments displaying firm nodules. Microscopic examination revealed a tumefactive malignant-appearing epithelioid proliferation involving the peritoneum, focally invading the underlying fat. Immunohistochemically, the tumor cells expressed keratin AE1/AE3, CK7, CK5/6, Calretinin, WT1 and D2-40, and were negative for CEA and MOC31. The findings were consistent with MPM, epithelioid type. The patient's condition continued to decline with increasing abdominal distension during the month following the original diagnosis. While atypical mesothelial hyperplasia has been described in association with long standing VPS, well-documented cases of MPM have not been previously reported in such context.

Polycystic ovarian syndrome and Cushing's syndrome: a persistent diagnostic quandary.

OBJECTIVE: To retrospectively review institutional records of female patients of reproductive age with Cushing's disease (CD) and determine if and how many had been previously diagnosed as having solely polycystic ovarian syndrome (PCOS). To determine whether clinical patterns might be useful in identifying appropriate candidates for hypercortisolism screening in women suspected of PCOS. STUDY DESIGN: The study included 50 patients with pathologically proven CD at Oregon Health & Science University, Northwest Pituitary Center between 2006 and 2011. Physical, clinical, and biochemical features for hypercortisolism were compared. RESULTS: Of 50 patients with pathologically proven CD, 26 were women of reproductive age. Of these, half had previously been diagnosed with and treated initially solely for PCOS. Hirsutism and menstrual abnormalities were more common in the group with an initial PCOS diagnosis than in the group with an initial CD diagnosis. CONCLUSIONS: Prolonged exposure to hypercortisolism has been linked with increased mortality and morbidity. Tests for hypercortisolism in all the PCOS cases we report led to an appropriate CD diagnosis. Future research should focus on when and which (if not all) women with suspected PCOS should be tested for hypercortisolism.