An Unusual Cause of Longstanding Diarrhea.

Colchicine is an alkaloid drug used in multiple medical conditions. It has a narrow therapeutic index, and gastrointestinal symptoms can occur at the beginning or after long-term therapy. Unintentional toxicity is common and has a high mortality rate when missed. Histopathologic recognition is challenging, and timely identification is conducted to improve patients' outcomes. We describe the case of a 77-year-old female who presented to the emergency room for dehydration, longstanding diarrhea, and weight loss. Upper and lower endoscopies showed erythematous mucosa without bleeding in the gastric antrum and an unremarkable duodenum and colon. Duodenal biopsies demonstrated partial villous atrophy with elongated glands and numerous arrested ring mitoses, consistent with colchicine toxicity.

Case Report: Metastatic renal cell carcinoma to the thyroid- A rare encounter.

Background: Renal cell carcinoma (RCC) accounts for approximately 4% of new adult cancers. By fine needle aspiration, identification of metastatic RCC to thyroid is challenging; therefore, surgical resection is indicated for definitive characterization. Our report surveys metastatic RCC to thyroid in our hospital. Methods: Twenty years retrospective review of electronic records in our institution identified five patients with metastatic renal cell carcinoma to the thyroid. We analyzed patient charts and pathology reports to evaluate clinical parameters and therapy. Results: In all cases, the original RCC was of clear cell type. Pathologic tumor stage ranged from pT1a to pT3a, Fuhrman nuclear grade varied from 2 to 4 and angiolymphatic invasion was noted in one case. In three patients, RCC in the thyroid occurred as an oligometastasis with no evidence of disease in the nephrectomy bed or other parts of the body. In two patients, concomitant recurrent RCC and metastases to liver, lung, brain and chest wall were documented. The thyroid metastases were found approximately 10 years after completion of nephrectomy with a range of 0-21 years. Three thyroid fine needle aspirations correctly identified the disease, one was negative, and one was classified as atypical cells present, suspicious for RCC. Conclusion: The thyroid gland is an uncommon location for RCC metastasis and can appear across a wide range of initial stages and grades of the disease. Thyroid metastases occurred as late as 21 years from the initial tumor resection. Increased awareness and a high index of suspicion are needed to detect metastasis, as they can be found in atypical locations and mimic primary disease.

Podocyte specific deletion of PKM2 ameliorates LPS-induced podocyte injury through beta-catenin.

BACKGROUND: Acute kidney injury (AKI) is associated with a severe decline in kidney function caused by abnormalities within the podocytes' glomerular matrix. Recently, AKI has been linked to alterations in glycolysis and the activity of glycolytic enzymes, including pyruvate kinase M2 (PKM2). However, the contribution of this enzyme to AKI remains largely unexplored. METHODS: Cre-loxP technology was used to examine the effects of PKM2 specific deletion in podocytes on the activation status of key signaling pathways involved in the pathophysiology of AKI by lipopolysaccharides (LPS). In addition, we used lentiviral shRNA to generate murine podocytes deficient in PKM2 and investigated the molecular mechanisms mediating PKM2 actions in vitro. RESULTS: Specific PKM2 deletion in podocytes ameliorated LPS-induced protein excretion and alleviated LPS-induced alterations in blood urea nitrogen and serum albumin levels. In addition, PKM2 deletion in podocytes alleviated LPS-induced structural and morphological alterations to the tubules and to the brush borders. At the molecular level, PKM2 deficiency in podocytes suppressed LPS-induced inflammation and apoptosis. In vitro, PKM2 knockdown in murine podocytes diminished LPS-induced apoptosis. These effects were concomitant with a reduction in LPS-induced activation of ß-catenin and the loss of Wilms' Tumor 1 (WT1) and nephrin. Notably, the overexpression of a constitutively active mutant of ß-catenin abolished the protective effect of PKM2 knockdown. Conversely, PKM2 knockdown cells reconstituted with the phosphotyrosine binding-deficient PKM2 mutant (K433E) recapitulated the effect of PKM2 depletion on LPS-induced apoptosis, ß-catenin activation, and reduction in WT1 expression. CONCLUSIONS: Taken together, our data demonstrates that PKM2 plays a key role in podocyte injury and suggests that targetting PKM2 in podocytes could serve as a promising therapeutic strategy for AKI. TRIAL REGISTRATION: Not applicable. Video abstract.

Forty-eight-year-old female MUTYH carrier presenting with five concurrent primary cancers.

BACKGROUND: MUTYH-associated polyposis is a rare disorder resulting from mutations involved in DNA mismatch repair. This results in an increased susceptibility to colonic adenomatosis and other cancers. Studies have examined the resulting frequency of extracolonic manifestations; however, these typically occur alone, concurrently, or temporally separate from an already diagnosed colorectal cancer in individuals with a biallelic mutation. CASE: Reported here is a case of five distinct primary neoplasms presenting simultaneously in a patient monoallelic for an MYH mutation. These neoplasms included squamous cell carcinoma of the vulva, rectal adenocarcinoma, synchronous anal adenocarcinoma, papillary thyroid carcinoma, and ovarian serous psammocarcinoma. Throughout her course, she underwent multiple surgical procedures, neoadjuvant chemoradiation, with further adjuvant therapy, and treatment ongoing. Due to her unique presentation, she underwent genetic testing that demonstrated she was monoallelic for an MYH mutation. CONCLUSION: The patient had a positive response to her treatment and surgical procedures with ongoing adjuvant therapy. She will continue to undergo further genetic testing, and testing for her children is being considered. This case demonstrates a unique presentation associated with a monoallelic MYH mutation that is not described in the current literature and warrants further investigation.

Cytologic analysis of vitreous fluids: A retrospective review of our 24 years of experience.

BACKGROUND: Cytologic analysis of vitreous fluid is an important component in diagnosis of vitreitis. No standard reporting guidelines exist for these specimens. This study chronicles our 24 years experience and proposes a tentative diagnostic model. METHODS: Retrospective cytology reports review and database study. Clinical indications, cytologic patterns, ancillary studies performed, and diagnoses were recorded. RESULTS: 176 samples from 160 patients were included and main cytologic patterns are reflected in Table 1. Most fluids were negative for malignancy (88%) and patterns IIB (53%) and IIA (19%) were dominant. The non-diagnostic rate was 7%; atypical and suspicious categories represented <0.5% of fluids tested and only 2% were positive for malignancy (3 intraocular lymphoma and one melanoma). Clinical indications for fluid examination were infection/inflammation (59%), to rule out lymphoma (11%), amyloidosis (3%), melanoma (2%), or to investigate intraocular hemorrhage. Fungal elements were demonstrated in 7 cases. No viral inclusions were appreciated; however, one case was positive for HSV 2 by IHC and 2 were negative by PCR. One case had Gram + cocci. Flow cytometry studies were suboptimal in 6 fluids, negative for an aberrant lymphocyte population in 11, and positive for high grade lymphoma in 3 cases. Atypical, suspicious and positive for melanoma were reported in 3 samples. Amyloid was identified in 1 aspirate. CONCLUSIONS: Cytologic analysis of vitreous fluid is a useful tool. Modern techniques like flow cytometry and PCR testing further expand the diagnostic possibilities. Standardization of diagnostic terminology will aid clinicians caring for patients suffering from ocular disease.

Improving ROSE: Discrepant touch preparation and histology findings in cytology of renal masses: A 10-year retrospective review.

BACKGROUND: The number of "renal incidentalomas" is on the rise due to increasing use of radiologic studies. Image-guided core needle biopsies (CNB) with touch preparations are performed to guide specimen collection and triage of sample for additional studies. Results allow the clinical team to make appropriate treatment decisions. DESIGN: Our electronic database was searched for a 10-year period to identify 180 image-guided biopsies of renal masses with rapid on-site evaluations (ROSE) and corresponding biopsy/resection specimens. Touch preparations were classified as non-diagnostic, negative/benign, adequate/positive for malignancy/oncocytic predominance, or atypical. These results were compared to the final diagnosis on the biopsy or resection specimen (if available). Diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values were determined. Non-diagnostic cases and cases in which ROSE and final diagnosis were discordant were reviewed by cytopathologists blinded to the original interpretation to reconcile discrepancies and highlight interpretation pitfalls. RESULTS: A ROSE diagnosis was rendered in 133 of 180 cases; 47 cases were non-diagnostic. Of the 133 diagnostic cases, the ROSE diagnosis was concordant with the core biopsy final diagnosis in 125 cases, yielding a diagnostic accuracy of 94%. The overall sensitivity was calculated to be 80.1%; specificity 72.4%; positive predictive value 94%; and negative predictive value 41.2%. CONCLUSIONS: Touch preparation slides are vital but imperfect tools in evaluating renal masses. In our study, distinction between malignant and benign samples was accomplished in most cases (94% accuracy), but there are limitations. Awareness of interpretation pitfalls allows informed decisions to be made regarding specimen collection and patient management.

Squamous cell carcinoma in serous effusions: Avoiding pitfalls in this rare encounter.

BACKGROUND: With advent of personalized medicine, precise classification of malignant tumors becomes essential. Squamous cell carcinoma (SCC) is rarely found in serous effusions and has morphologic and immunohistochemical (IHC) overlap with other neoplasms. METHODS: 17-year review identified 49 fluids from 26 patients where SCC was recognized. RESULTS: SCC was more frequent in pleural fluid (84%) and rare in other effusions. Lung SCC was common (65%), followed by head and neck (16%), with other origins less represented. 19 samples were diagnosed positive for SCC, 12 were reported as non-small cell carcinoma and 13 were atypical/suspicious. Two were false negative (on hypocellular smears) and one was false positive (smear with small orangeophilic squamous-like cells). Two fluids were diagnosed as adenocarcinoma on smears and SCC on cellblocks after IHC. A chi-square test showed the correct diagnosis more often on cellblocks than smears (P-value = .0005) and all false positive, negative or misclassifications were done on cytology smears. Ber EP4 and MOC 31 immunostains were positive in most cases when performed, and the most specific immunostains for SCC were p63 and p40. Negative mucin stains were helpful. Cytology smears are imperfect tools in evaluation of body fluids and SCC can be misclassified as adenocarcinoma on smears alone. Orangeophilic cytoplasm can lead to false positive results. The most useful stains for identification were p40, p63, and mucicarmine. CONCLUSION: The combination of clinical history with cellblock preparation and appropriate IHCs is the best method to ensure a correct diagnosis.

Bariatric Radioembolization: A Pilot Study on Technical Feasibility and Safety in a Porcine Model.

PURPOSE: To evaluate feasibility of left gastric artery (LGA) yttrium-90 ((90)Y) radioembolization as potential treatment for obesity in a porcine model. MATERIALS AND METHODS: This study included 8 young female pigs (12-13 weeks, 21.8-28.1 kg). Six animals received infusions of (90)Y resin microspheres (46.3-105.1 MBq) into the main LGA and the gastric artery arising from the splenic artery. Animal weight and serum ghrelin were measured before treatment and weekly thereafter. Animals were euthanized 69-74 days after treatment, and histologic analyses of mucosal integrity and ghrelin immunoreactive cell density were performed. RESULTS: Superficial mucosal ulcerations < 3.0 cm(2) were noted in 5 of 6 treated animals. Ghrelin immunoreactive cell density was significantly lower in treated versus untreated animals in the stomach fundus (13.5 vs 34.8, P < .05) and stomach body (11.2 vs 19.8, P < .05). Treated animals gained less weight than untreated animals over the study duration (40.2 kg ± 5.4 vs 54.7 kg ± 6.5, P = .053). Average fundic parietal area (165 cm(2) vs 282 cm(2), P = .067) and average stomach weight (297.2 g vs 397.0 g, P = .067) were decreased in treated versus untreated animals. Trichrome staining revealed significantly more fibrosis in treatment animals compared with control animals (13.0 vs 8.6, P < .05). No significant differences were identified in plasma ghrelin concentrations (P = .24). CONCLUSIONS: LGA (90)Y radioembolization is promising as a potential treatment for obesity. A larger preclinical study is needed to evaluate the safety and efficacy of this procedure further.

How Sensitive Is the Upper Gastrointestinal Tract to 90Y Radioembolization? A Histologic and Dosimetric Analysis in a Porcine Model.

In 90Y radioembolization, nontarget embolization to the stomach or small bowel can result in gastrointestinal injury, a rare but difficult to manage clinical complication. However, dosimetric thresholds for toxicity to these tissues from radioembolization have never been evaluated in a controlled setting. We performed an analysis of the effect of 90Y radioembolization in a porcine model at different absorbed-dose endpoints. METHODS: Six female pigs underwent transfemoral angiography and infusion of 90Y-resin microspheres into arteries supplying part of the gastric wall. Esophagogastroduodenoscopy was performed after 4 wk to assess interim gastrointestinal health. Animals were monitored for side effects for 9 wk after 90Y infusion, after which they were euthanized and their upper gastrointestinal tracts were excised for analysis. Histologic sections were used to map microsphere location, and a microdosimetric evaluation was performed to determine the absorbed-dose profile within the gastrointestinal wall. RESULTS: 90Y radioembolization dosages from 46.3 to 105.1 MBq were infused, resulting in average absorbed doses of between 35.5 and 91.9 Gy to the gastric wall. No animal exhibited any signs of pain or gastrointestinal distress through the duration of the study. Excised tissue showed 1-2 small (<3.0 cm2) healed or healing superficial gastric lesions in 5 of 6 animals. Histologic analysis demonstrated that lesion location was superficial to areas of abnormally high microsphere deposition. An analysis of microsphere deposition patterns within the gastrointestinal wall indicated a high preference for submucosal deposition. Dosimetric evaluation at the luminal mucosa performed on the basis of microscopic microsphere distribution confirmed that 90Y dosimetry techniques conventionally used in hepatic dosimetry provide a first-order estimate of absorbed dose. CONCLUSION: The upper gastrointestinal tract may be less sensitive to 90Y radioembolization than previously thought. Lack of charged-particle equilibrium at the luminal mucosa may contribute to decreased toxicity of 90Y radioembolization compared with external-beam radiation therapy in gastrointestinal tissue. Clinical examples of injury from 90Y nontarget embolization have likely resulted from relatively large 90Y activities being deposited in small tissue volumes, resulting in absorbed doses in excess of 100 Gy.

Multiple squamous cells in thyroid fine needle aspiration: Friends or foes?

BACKGROUND: Abundant squamous cells are rarely encountered in thyroid FNA with only few case reports noted in the literature. Their presence and cytologic features may pose a diagnostic dilemma and challenges for proper classification and follow-up. We intend to gain more insight into the frequency of this finding and its clinical significance. DESIGN: Our electronic records were searched over 16 years to reveal 15 thyroid FNAs with abundant squamous cells. The available cytology and surgical resection slides were reviewed and radiologic records and clinical follow-up was documented. RESULTS: Only 15 out of 8811 thyroid FNAs from our department contained predominantly squamous cells (0.17%) of which two were interpreted as nondiagnostic, four as atypical, eight as benign, and one malignant. Surgical follow-up was available in eight cases only with benign lesions representing the majority of the cases (squamous metaplasia in Hashimoto thyroiditis, benign epidermoid/branchial cleft or thyroglossal duct cysts, and one case squamous cell carcinoma). The cases without surgical resection were stable on subsequent ultrasound studies. CONCLUSION: Thyroid aspirates with predominance of squamous cells cannot be classified in the current Bethesda categories. Even when interpreted as atypical or equivocal, the squamous cells present in our small case series were mostly benign. The only malignant case was easily identified cytologically because of its higher degree of differentiation. The most common pitfall for atypical squamous cells in these aspirates was squamous metaplasia in the setting of Hashimoto thyroiditis and degenerative changes. Diagn. Cytopathol. 2016;44:676-681. © 2016 Wiley Periodicals, Inc.

The clinical correlation of phosphatase and tensin homolog on chromosome 10, phosphorylation of AKT to an activated state, and odontogenic ameloblast-associated protein in gastrointestinal stromal tumors.

BACKGROUND: Approximately 15% of gastrointestinal stromal tumors (GISTs) will not respond to tyrosine kinase inhibitors and drug resistance can develop over time. For refractory tumors, additional therapies are needed. Odontogenic ameloblast-associated protein (ODAM) is expressed in some epithelial malignancies and can correlate with clinical outcomes. This study evaluated ODAM and its relationship to phosphatase and tensin homolog on chromosome 10 (PTEN) and phosphorylation of AKT to an activated state (pAKT) in GISTs. MATERIALS AND METHODS: Ninety-five distinct tumor specimens from 79 patients were identified. Morphologic features and clinical data were recorded for all tumors. Risk of recurrence was calculated using the Memorial Sloan-Kettering nomogram. Immunohistochemistry was performed using antibodies to ODAM, PTEN, and pAKT. Immunoreactivity was assessed for both cytoplasmic and nuclear expression. Staining patterns were correlated with clinical outcomes. RESULTS: Increasing cytoplasmic ODAM staining correlated with a lower recurrence score (P = 0.002), a lower mitotic rate (P = 0.0001), and smaller tumor size (P = 0.038). Increasing pAKT cytoplasmic staining correlated with a higher recurrence score (P = 0.037) and a higher mitotic rate (P = 0.036). ODAM and pAKT expression in the nucleus was associated with tumor origin. PTEN nuclear expression increased with increasing mitotic rate. pAKT expression increased in the cytoplasm and nucleus in high-risk tumors. CONCLUSIONS: Risk of recurrence correlated with cytoplasmic expression of ODAM and pAKT, whereas nuclear expression did not predict recurrence. The staining pattern for ODAM and pAKT in the cytoplasm may further clarify the risk of recurrence beyond the available nomograms. The increased expression of pAKT in the cytoplasm and nucleus of high-risk tumors suggests a potential target for systemic therapy.

Undifferentiated Malignant Neoplasm Involving Parotid and Thyroid: Sampling and PAX8 Cross-Reactivity Can Obscure the Diagnosis of Lymphoma.

Poorly differentiated malignant neoplasia arising within the head and neck region may originate from diverse sources. We report a case of a cytologically undifferentiated malignant neoplasm clinically presenting as masses involving thyroid and parotid. Although PAX8 was immunoreactive and thus worrisome for anaplastic thyroid carcinoma, the tumor was eventually proven to represent PAX5 positive diffuse large B-cell lymphoma expressing cross-reactivity with polyclonal PAX8 antibody. Cross-reactivity between commercially available polyclonal PAX8 and PAX5 immunostains has been described in the literature but is not widely known, and it is a potential pitfall for making a misdiagnosis. This distinction can have importance in selection of subsequent clinical therapy and should be considered in choice of immunohistochemical stains for diagnostic purposes.

Thyroid-like follicular carcinoma of the kidney: one case report and review of the literature.

OBJECTIVES: Thyroid-like follicular carcinoma of the kidney continues to confound the practicing pathologist with its close resemblance to the follicular variant of thyroid carcinoma, as well as other benign and malignant entities. Our goal is to expand the knowledge of this rare renal cell carcinoma subtype, which is morphologically similar to follicular carcinoma of the thyroid but lacks expression of characteristic thyroid immunohistochemical markers such as TTF-1 and thyroglobulin. METHODS: We evaluated the gross, histologic, immunohistochemical, and fluorescence in situ hybridization (FISH) studies of a new case and performed a comprehensive review of the literature. RESULTS: The lesion was spongy and well-circumscribed. Microscopically it showed variably sized follicular structures, filled with abundant, deeply eosinophilic, colloid-like material. At the periphery, it displayed areas resembling metanephric adenoma and early stages of nephrogenesis. The tumor cells strongly expressed CK7, PAX-8, PAX-2, vimentin, EMA, and CK19 immunostains. Other markers, such as CD10, RCC, HBME-1, thyroglobulin, and TTF-1, were not immunoreactive. The tumor was negative for trisomy of both 7 and 17 and showed borderline monosomies (losses) of both chromosomes in FISH studies. CONCLUSIONS: Five years of preoperative observation and lack of recurrence bring further insight into the slow progressive nature of this neoplasm and support a low malignant potential. Proper identification is important to secure adequate treatment and follow-up.

Groove pancreatitis: a brief review of a diagnostic challenge.

Groove pancreatitis is an uncommon, yet well-described, type of focal chronic pancreatitis, affecting "the groove"-the area between the head of the pancreas, the duodenum, and the common bile duct. Men aged 40 to 50 years are most commonly affected, with a history of alcohol abuse frequently disclosed. Clinical manifestations are similar to other forms of chronic pancreatitis, and vomiting secondary to duodenal stenosis is the main feature. It is postulated that pancreatitis in the groove area arises from obstruction of pancreatic juices in the ductal system, causing fibrosis and stasis with resultant inflammation of surrounding structures. The minor papilla is frequently the anatomic area of preferential involvement. Groove pancreatitis poses diagnostic challenges, forming a "pseudotumor" that mimics pancreatic carcinoma. The distinction is important, although often impossible to make because of their similar presentation, with groove pancreatitis usually affecting younger patients. Most patients are successfully treated with pancreaticoduodenectomy when definitive pathologic diagnoses can be made.

Penoscrotal mass: a rare presentation of herpes simplex virus infection.

A 55-year-old man presents with a 10-cm condylomatous penoscrotal mass. Final pathology after surgical removal reveals a rare vegetative lesion with underlying herpes simplex virus infection. Along with neoplasia, infectious causes must remain in the differential diagnosis in the immunocompromised patient who presents with an atypical lesion.