Smooth muscle tumors of the gastrointestinal tract: an analysis of prognostic features in 407 cases.

Smooth muscle tumors represent the second most common mural mesenchymal neoplasm in the gastrointestinal tract, but established criteria for prognostic assessment of these tumors are lacking. A large cohort of surgically resected intramural gastrointestinal smooth muscle tumors from 31 institutions was analyzed to identify potential prognostic features. Pathologic features were assessed by expert gastrointestinal and/or soft tissue pathologists at each center. Immunohistochemical confirmation was required. A total of 407 cases from the esophagus (n = 97, 24%), stomach (n = 180, 44%), small bowel (n = 74, 18%), and colorectum (n = 56, 14%) were identified. Patients ranged in age from 19 to 92 years (mean 55 years), with a slight female predominance (57%). Mean tumor size was 5.4 cm, with the largest tumor measuring 29 cm. Disease progression following surgery, defined as local recurrence, metastasis, or disease-related death, occurred in 56 patients (14%). Colorectal tumors were most likely to progress, followed by small bowel and gastric tumors. None of the esophageal tumors in this series progressed. Receiver operator characteristic analysis identified optimal cutoffs of 9.8 cm and 3 mitoses/5 mm2 for discriminating between progressive and non-progressive tumors. Histologic features strongly associated with progression by univariate analysis included moderate-to-severe atypia, high cellularity, abnormal differentiation (defined as differentiation not closely resembling that of normal smooth muscle), tumor necrosis, mucosal ulceration, lamina propria involvement, and serosal involvement (P < 0.0001 for all features). Age, sex, and margin status were not significantly associated with progression (P = 0.23, 0.82, and 0.07, respectively). A risk assessment table was created based on tumor site, size, and mitotic count, and Kaplan-Meier plots of progression-free survival for each subgroup revealed progression-based tiers. Based on our findings, it appears that nonesophageal gastrointestinal smooth muscle tumors measuring >10 cm and/or showing ≥3 mitoses/5 mm2 may behave aggressively, and therefore close clinical follow-up is recommended in these cases.

Metastatic Mixed Adeno-Neuroendocrine Carcinoma of the Colon to the Liver with Multiple Peritoneal Deposits: A Case Report.

BACKGROUND Metastatic mixed adeno-neuroendocrine carcinoma (MANEC) is a rare malignancy. It is characterized by the presence of both neuroendocrine and epithelial components, each of which constitute at least 30% of the lesion to establish the diagnosis. CASE REPORT A 48-year-old man presented with a 1-month history of right upper-quadrant pain and unintentional weight loss of 18 kg. He was also complaining of constipation and fatigue for 6 days. The initial diagnosis from a referring hospital was colon cancer with liver metastasis based on a computed tomography (CT) scan of the chest, abdomen and pelvis. After re-evaluation at our hospital, the scan revealed multiple peritoneal deposits in addition to the previously reported findings. A colonoscopy and biopsy were performed, after which the histopathological examination demonstrated a mixed poorly differentiated large cell neuroendocrine carcinoma and adenocarcinoma. Based on the imaging and histopathology reports, he was diagnosed with a poorly differentiated MANEC of the colon with liver metastasis and multiple peritoneal deposits. His lesions were deemed unresectable, and he was referred to the oncology department for palliative care. There he received a total of 9 cycles of cisplatin and etoposide for 8 months. His CT scan showed a regression of the primary tumor indicating a good response to chemotherapy. The patient is still following up with his medical oncologist. CONCLUSIONS Although it is rare, MANEC is a complex neoplasm that requires a high index of suspicion to diagnose due to its nonspecific presentation. It is confirmed through histopathology and immunohistochemistry of the tumor biopsy. Imaging is performed for staging, with most patients presenting at advanced stages with metastases. The only curative option is complete surgical resection of both the primary and metastatic lesion. Many cases, however, are regarded as unresectable and are referred for palliative treatment.

Diagnosis of Congenital Hepatic Fibrosis in Adulthood.

OBJECTIVES: We studied clinicopathologic features of congenital hepatic fibrosis (CHF) that could aid the diagnosis of this relatively rare condition during adulthood. METHODS: Five consecutive adult CHF cases were identified in a single institution. RESULTS: Clinical manifestations of CHF varied from asymptomatic to requiring liver transplantation. Three of five cases had other disease associations, including Joubert syndrome, Caroli disease, polycystic kidney disease, and congenital anomaly of hepatic vasculature. No unique common radiologic findings were found. Histologically, all cases showed characteristic abnormal interlobular bile ducts embedded in fibrotic portal stroma, with varying degrees of liver fibrosis. CONCLUSIONS: While other disease associations and characteristic liver histomorphology are helpful clues to suspect the diagnosis of CHF in adult patients, other differential diagnoses should be excluded clinically and radiologically. This study highlights the importance of a multidisciplinary diagnostic approach by pathologists, radiologists, and hepatologists for the accurate diagnosis of CHF during adulthood.

Unexpected expression of mismatch repair protein is more commonly seen with pathogenic missense than with other mutations in Lynch syndrome.

It has been observed that some patients with colorectal cancer due to germline or double somatic pathogenic variants in the mismatch repair (MMR) genes may have intact protein expression in their tumors as assessed by immunohistochemistry (IHC). This has been speculated to occur more frequently in Lynch syndrome (LS) cases due to pathogenic missense mutations, leading to expression of a full-length but nonfunctional protein with retained antigenicity. Our goals were to study the frequency of unexpected MMR expression in colorectal cancers among LS cases with missense mutations, LS cases with truncating mutations, as well as cases with double somatic MMR mutations and evaluate if the unexpected MMR expression is more common in certain categories. IHC slides were available for 82 patients with MMR deficiency without methylation, which included 56 LS cases and 26 double somatic MMR mutation cases. Sixteen of 82 MMR-defective cases showed unexpected MMR expression, with 10 cases showing tumor staining weaker than the control and 6 cases (7%) showing intact staining. Unexpected MMR expression was most commonly seen with LS cases with missense mutations (4 of 9, 44%), followed by MMR double somatic mutation cases (7 of 26, 27%), and finally by LS cases with truncating mutations (5 of 47, 11%). Cautious interpretation of MMR IHC is advised when dealing with tumor staining that is weaker than the control regardless of the percentage of tumor staining as these cases may harbor pathogenic MMR gene mutations. Missense mutations may account for some LS cases that may be missed by IHC alone. Strict adherence to proper interpretation of IHC with attention to staining intensity and the status of heterodimer partner protein will prevent many potential misses.

Lipomatous tumors of adrenal gland: A case series of 5 patients and review of the literature.

INTRODUCTION: Lipomatous tumors of the adrenal glands are a diverse group of tumors characterized by the composition of adipose tissue. This group of tumors include myelolipomas, angiomyolipomas (AML), lipomas, and teratomas. They are usually benign, non-functioning tumors, and they account for 5% of all primary adrenal tumors. This study aimed to elucidate the management of the initial size of the adrenal mass and symptoms of presentation. We provide a succinct literature review regarding angiomyolipomas tumors of the adrenal glands. PRESENTATION OF CASES: Here, we report 5 cases of lipomatous tumors of the adrenal glands. All 5 tumors were non-functioning. Four of them were myelolipoma, and one was AML. Two cases of myelolipoma presented with flank pain, while the rest of the 3 cases presented with hypochondrium pain. Three cases of myelolipoma were managed with laparoscopic adrenalectomy, one case of myelolipoma was converted from laparoscopic to open adrenalectomy because of abdominal adhesions, and the last case was AML and was managed with open adrenalectomy. All patients had an uneventful recovery with regular follow-up. DISCUSSION: Myelolipoma, the most common lipomatous tumor of the adrenal gland, consists of a mixture of bone morrow element and adipose tissue. AML consists of a mixture of a thick-walled blood vessel, smooth muscle, and adipose tissue. They mimic many different benign and malignant tumors on radiography, and the histopathological examination is still needed to confirm the diagnosis. There is still controversy in the management of these tumors. Usually, the management is individualized on each case. Reporting of these tumors are increasing due the wide-spread use of modern imaging modalities. CONCLUSION: Adrenal lipomatous tumors are uncommon but with the increase use of imaging modalities their detection has increased. Further studies are needed to establish guidelines in the management of these tumors, especially that they can mimic malignant conditions.

Microsatellite Instability Occurs in a Subset of Follicular Thyroid Cancers.

BACKGROUND: Inactivation of DNA mismatch repair (MMR) and the resulting microsatellite instability (MSI) are frequently observed in endometrial, stomach, and colorectal cancers, as well as more rarely in other solid tumor types. The prevalence of MSI in thyroid cancer has not been explored in depth, although recent studies utilizing data from large cancer sequencing efforts such as The Cancer Genome Atlas indicate that MSI is absent or at least very rare in the most common and most well studied histologic subtype, papillary thyroid carcinoma. This study aimed to determine the prevalence of MSI in thyroid cancer by using a large series comprising all major histological subtypes. METHODS: A total of 485 thyroid cancer patients were screened for MSI/MMR deficiency, including all major histologic subtypes (195 papillary thyroid carcinoma, 156 follicular thyroid carcinoma [FTC], 50 anaplastic thyroid carcinoma, 65 medullary thyroid carcinoma, and 17 poorly differentiated thyroid carcinomas) by using a combination of polymerase chain reaction-based detection, immunohistochemistry, and next-generation sequencing. RESULTS: A total of four tumors were MSI-high and had loss of MMR protein expression, all of which were from FTC patients. Whole-exome sequencing was performed on two MSI-high FTCs and revealed a hemizygous loss of function mutation in MSH2 in one tumor. CONCLUSIONS: Based on these data, it is estimated that the overall prevalence of MSI in FTC is 2.5%, and MSI is either entirely absent or rare in other histology subtypes of thyroid carcinoma. These findings highlight the importance of testing for MSI in FTC.

Challenges to "Classic" Esophageal Candidiasis: Looks Are Usually Deceiving.

Objectives: We undertook the first case control study of histologically confirmed esophageal candidiasis (EC). Methods: A computer search from July 2012 through February 2015 identified 1,011 esophageal specimens, including 40 cases of EC and 20 controls. Results: The EC incidence was 5.2%; it was associated with immunosuppression and endoscopic white plaques and breaks. Smoking was a predisposing factor, and alcohol was protective. EC had no unique symptoms, and 54% of endoscopic reports did not suspect EC. Important histologic clues included superficial and detached fragments of desquamated and hyper-pink parakeratosis, acute inflammation, intraepithelial lymphocytosis, dead keratinocytes, and bacterial overgrowth. Thirty percent had no neutrophilic infiltrate. Pseudohyphae were seen on H&E in 92.5% (n = 37/40). "Upfront" periodic acid-Schiff with diastase (PAS/D) on all esophageal specimens would have generated $68,333.49 in patient charges. Our targeted PAS/D strategy resulted in $13,044.87 in patient charges (cost saving = 80.9%, $55,288.62). Conclusions: We describe the typical morphology of EC and recommend limiting PAS/D to cases where the organisms are not readily identifiable on H&E and with at least one of the following: (1) ulcer, (2) suspicious morphology, and/or (3) clinical impression of EC.