SWI/SNF chromatin remodeling complex in pancreatic ductal adenocarcinoma: Clinicopathologic and immunohistochemical study.

The SWItch/Sucrose Non-Fermentable (SWI/SNF) complex is a multimeric protein involved in transcription regulation and DNA damage repair. SWI/SNF complex abnormalities are observed in approximately 14-34 % of pancreatic ductal adenocarcinomas (PDACs). Herein, we evaluated the immunohistochemical expression of a subset of the SWI/SNF complex proteins (ARID1A, SMARCA4/BRG1, SMARCA2/BRM, and SMARCB1/INI1) within our PDAC tissue microarray to determine whether SWI/SNF loss is associated with any clinicopathologic features or patient survival in PDAC. In our cohort, 13 of 353 (3.7 %) PDACs showed deficient SWI/SNF complex expression, which included 11 (3.1 %) with ARID1A loss, 1 (0.3 %) with SMARCA4/BRG1 loss, and 1 (0.3 %) with SMARCA2/BRM loss. All cases were SMARCB1/INI1 proficient. The SWI/SNF-deficient PDACs were more frequently identified in older patients with a mean age of 71.6 years (SD = 7.78) compared to the SWI/SNF-proficient PDACs which occurred at a mean age of 65.2 years (SD = 10.95) (P = 0.013). The SWI/SNF-deficient PDACs were associated with higher histologic grade, compared to the SWI/SNF-proficient PDACs (P = 0.029). No other significant clinicopathologic differences were noted between SWI/SNF-deficient and SWI/SNF-proficient PDACs. On follow-up, no significant differences were seen for overall survival and progression-free survival between SWI/SNF-deficient and SWI/SNF-proficient PDACs (both with P > 0.05). In summary, SWI/SNF-deficient PDACs most frequently demonstrate ARID1A loss. SWI/SNF-deficient PDACs are associated with older age and higher histologic grade. No other significant associations among other clinicopathologic parameters were seen in SWI/SNF-deficient PDACs including survival.

Clinicopathologic features and diagnostic challenges of small cluster pattern appendiceal neuroendocrine tumors.

Appendiceal neuroendocrine neoplasms (NENs) can present with various growth patterns including the traditional triad of histologic patterns-insular, trabecular and tubular. A small cluster pattern was also found in this study and the literature on this specific morphology is limited. In this study, we conducted a comprehensive review of appendiceal NENs from our institution over a ten-year period. Clinical and demographic data were obtained from medical records. Immunohistochemical stains were performed with antibodies specific for synaptophysin, chromogranin, INSM1, CD56, serotonin and peptide YY. The small cluster pattern was found in 29.4 % of all cases evaluated. The tumor cells in these cases were predominantly located at the distal tip of the appendix, associated with fibrous obliteration. These tumors were smaller in size and tended towards less advanced tumor stage, with reduced incidence of lymphovascular and/or perineural invasion. Chromogranin expression was identified in 76 % of these cases. There is a heterogeneous hormone profile with 46.7 % serotonin and 33.3 % peptide YY. In conclusion, the small cluster pattern NENs present with unique histological features and hormone expression profile. Among the various neuroendocrine markers, INSM1 showed superior diagnostic performance, with high sensitivity and minimal non-specific staining.

Malignant solitary fibrous tumor of the urinary bladder progressing to widespread metastases and death: a rare case report and literature review.

Solitary fibrous tumor (SFT) of the urinary bladder has been rarely reported and malignant bladder SFT is even rarer. Here we present a case of an African-American male with SFT of the urinary bladder (intermediate risk) initially treated by cystoprostatectomy at the age of 59 years. Eight years later, he developed recurrence with widespread metastases to the liver, lungs, and abdominal cavity. He then received temozolomide and bevacizumab with good disease control. However, treatment was paused due to declining performance status. Follow-up at 1 year demonstrated growth of the metastatic lesions. Despite restarting therapy, the patient expired, 11 years after the original diagnosis. Autopsy was performed and revealed widespread metastases within the abdominal cavity (abdominal sarcomatosis) as well as liver, bilateral lung, and diaphragmatic involvement. The cause of death was determined to be metastatic SFT. A comprehensive literature review was performed. Although SFTs are commonly considered benign, a subset of SFTs of the urinary bladder behave aggressively. Risk assessment and proper follow-up for recurrence and metastasis is necessary. The patient was also found at autopsy to have two gastrointestinal stromal tumors (GISTs) in the stomach and near the gastroesophageal junction. To the best of our knowledge, this is the first reported case of a primary urinary bladder SFT resulting in death or having concurrent, multifocal GISTs, and only the second case of a bladder SFT that developed metastases after the initial diagnosis.

Glutathione supports lipid abundance in vivo.

Cells rely on antioxidants to survive. The most abundant antioxidant is glutathione (GSH). The synthesis of GSH is non-redundantly controlled by the glutamate-cysteine ligase catalytic subunit (GCLC). GSH imbalance is implicated in many diseases, but the requirement for GSH in adult tissues is unclear. To interrogate this, we developed a series of in vivo models to induce Gclc deletion in adult animals. We find that GSH is essential to lipid abundance in vivo. GSH levels are reported to be highest in liver tissue, which is also a hub for lipid production. While the loss of GSH did not cause liver failure, it decreased lipogenic enzyme expression, circulating triglyceride levels, and fat stores. Mechanistically, we found that GSH promotes lipid abundance by repressing NRF2, a transcription factor induced by oxidative stress. These studies identify GSH as a fulcrum in the liver's balance of redox buffering and triglyceride production.

Gastric Perineurioma: A Case Report and Review of the Literature.

Perineuriomas of the gastrointestinal tract, formerly known as benign fibroblastic polyps, most commonly occur as polyps on screening colonoscopy, particularly in the distal colon. Gastric examples are exceedingly rare. We report the sixth patient with a gastric perineurioma in a 57-year-old female. Histologically, the lesion was composed of bland spindle cells without cytologic atypia or mitotic activity located in the gastric lamina propria. The spindled cells were strongly positive for GLUT1 and focally reactive for epithelial membrane antigen (EMA). The morphologic and immunophenotypic findings were those of gastric perineurioma.

Arid1a mutation suppresses TGF-ß signaling and induces cholangiocarcinoma.

Activating KRAS mutations and functional loss of members of the SWI/SNF complex, including ARID1A, are found together in the primary liver tumor cholangiocarcinoma (CC). How these mutations cooperate to promote CC has not been established. Using murine models of hepatocyte and biliary-specific lineage tracing, we show that Kras and Arid1a mutations drive the formation of CC and tumor precursors from the biliary compartment, which are accelerated by liver inflammation. Using cultured cells, we find that Arid1a loss causes cellular proliferation, escape from cell-cycle control, senescence, and widespread changes in chromatin structure. Notably, we show that the biliary proliferative response elicited by Kras/Arid1a cooperation and tissue injury in CC is caused by failed engagement of the TGF-ß-Smad4 tumor suppressor pathway. We thus identify an ARID1A-TGF-ß-Smad4 axis as essential in limiting the biliary epithelial response to oncogenic insults, while its loss leads to biliary pre-neoplasia and CC.

Gastrointestinal Tract Injury by Yttrium-90 Appears Largely Restricted to Resin Microspheres But Can Occur Years After Embolization.

Radioembolization therapy utilizes yttrium-90 (Y90) impregnated resin (SIR-Spheres) or glass (TheraSpheres) microspheres to selectively target hepatic lesions via transarterial radioembolization. Occasional cases of gastrointestinal tract injury, secondary to nontargeted delivery of microspheres, have been reported, but large descriptive pathology series are lacking. We identified 20 cases of histologically confirmed mucosal injury associated with Y90 from 17 patients and assessed the corresponding clinical and pathologic sequelae. The mucosal biopsies were obtained from 1 to 88 months following Y90 therapy (median: 5 mo). Most cases were gastric (17, 85%), while the remaining were duodenal. Endoscopic ulceration was seen in the majority of cases (16, 80%), and mucosal erythema in the remaining 4. Histologically, a majority (19, 95%) of cases showed rounded, dark blue to purple microspheres measuring 4 to 30 µm, consistent with resin microspheres. A single case with glass microspheres demonstrated 26 µm translucent beads. Histologic evidence of ulceration was appreciated in 14 (70%) cases, and the microspheres were clearly intravascular in 6 (30%). A foreign body giant cell reaction to the microspheres was uncommon (3 cases, 15%). We additionally performed a retrospective review of all gastrointestinal tissue obtained postprocedure from 784 sequential patients treated with Y90 microspheres. Three patients (0.4%) demonstrated the presence of resin microspheres upon histologic examination. No cases involving glass-based Y90 were identified ( P =0.0078), despite the majority of patients having received glass radioembolization (630, 80%). This increased risk of secondary sphere dissemination is likely related to the increased number of particles required per activity for resin versus glass microspheres. We conclude that Y90 microspheres may be encountered in the gastrointestinal tract years after initial liver-targeted therapy and, when present, are often associated with mucosal ulceration. This finding is less likely to be encountered in patients who received Y90 radioembolization utilizing glass microspheres.

Clinicopathologic Features of Gynecologic Malignancies Presenting Clinically as Colonic Malignancies.

OBJECTIVES: To systematically evaluate gynecologic malignancies (adnexal or uterine) causing gastrointestinal (GI) signs (eg, mass on colonoscopy) or symptoms (eg, bloody stools) clinically mimicking a GI primary malignancy. METHODS: The archives of 2 institutions were retrospectively reviewed for gynecologic malignancies clinically manifesting as colonic lesions. For each case, available radiologic, endoscopic, and histologic findings were recorded. RESULTS: We identified 16 cases: 13 biopsies and 3 resections. The masses were localized in the rectosigmoid (14 cases [88%]), right (1 case [6%]), and transverse (1 case [6%]) colon. Gastrointestinal-type complaints included abdominal pain, weight loss, hematochezia, and obstruction; 1 case was asymptomatic and found during screening colonoscopy. Nine patients (56%) had no known prior gynecologic malignancy, and in only 2 of these patients was there some clinical suspicion of a noncolonic primary malignancy. Most cases (13 [81%]) were serous carcinoma, usually high-grade adnexal or primary peritoneal. Six cases (38%) directly extended into the colon, and 7 (44%) metastasized; route of spread was unclear in the others. Only 1 case (6%) showed mucosal involvement, and none showed desmoplasia or dirty necrosis. Four of the 13 serous carcinomas (31%) showed psammoma bodies. CONCLUSIONS: Advanced gynecologic malignancies, most commonly serous carcinoma, can rarely manifest as GI lesions. Clues to noncolonic origin on biopsy include lack of colonic mucosal involvement/dysplasia, desmoplasia, or dirty necrosis.

Interobserver agreement in the diagnosis of anal dysplasia: comparison between gastrointestinal and gynaecological pathologists and utility of consensus conferences.

AIMS: Management of anal dysplasia relies upon the accurate diagnosis of anal biopsy specimens. As institutions move towards subspecialty signout (SSSO), decisions must be made regarding whether to assign anal biopsies to the gastrointestinal (GI) or gynaecological (GYN) pathology service. MATERIALS AND RESULTS: We identified 200 archival tissue biopsies of anal mucosa and circulated them among three GI pathologists and three GYN pathologists. Each pathologist separately scored each biopsy as normal, atypical, low-grade squamous intra-epithelial lesion (LSIL) or high-grade squamous intra-epithelial lesion (HSIL). Every case that was called HSIL by at least one pathologist was stained with p16 immunostain and a 'gold standard' interpretation of whether or not a case represented HSIL was made. The GI pathologists agreed on 97 (49%) cases prior to consensus; the GYN pathologists agreed on 33 (17%). The sensitivities of the three GI pathologists in detecting HSIL against the 'gold standard' were 47, 100 and 21% and for the GYN pathologists the sensitivities were 74, 89 and 84%; the sensitivities of the GI and GYN consensus diagnoses were 74% each. The specificities of the three GI pathologists in detecting HSIL were 99, 90 and 100% and for the GYN pathologists the specificities were 99, 92 and 91%; the specificities of both the GI and GYN consensus diagnoses were 100%. CONCLUSIONS: A mild to moderate degree of interobserver variability exists in the diagnosis of anal dysplasia among pathologists. Our study indicates the utility of some form of consensus conference, as overall agreement among GI pathologists and among GYN pathologists improved following in-person consensus.

Clinicopathologic features of metastatic small cell carcinoma of the prostate to the liver: a series of four cases.

BACKGROUND: Small cell neuroendocrine carcinoma of the prostate (SCNECP) is a rare, aggressive subtype of prostate carcinoma. Most SCNECP arise from conventional prostate adenocarcinoma (CPAC) treated with androgen deprivation therapy (ADT). CASE PRESENTATIONS: We identified four cases of CPAC treated with ADT, which evolved to SCNECP with liver metastasis. The average interval between the diagnosis of CPAC and SCNECP was 102 months (range: 12 to 168). Histologically, the tumors showed nests of cells with high nuclear:cytoplasmic ratios, granular chromatin, and frequent mitoses. All cases were synaptophysin, chromogranin, and AE1/AE3 positive, with a Ki-67 labeling index ≥70%. NKX3.1 was negative in all but one case and TTF-1 was positive in half. Weak ERG positivity by IHC was seen in one case which also demonstrated the TMPRSS2-ERG gene rearrangement; all other cases were negative for ERG by IHC. Serum prostate specific antigen (PSA) levels were normal to near-normal in all. The median interval between the diagnosis of SCNECP and death was 3.25 months (range: 0.75 to 26). CONCLUSIONS: Our case series highlights the importance of considering a prostate primary, even in the setting of normal PSA levels and loss of prostate markers, when diagnosing neuroendocrine carcinoma in the liver. Further, we emphasize the significance of diagnosing SCNECP that metastasizes to the liver, as it portends a particularly dismal prognosis.

Risk factors for progression of appendiceal neuroendocrine tumours: low-stage tumours <5 mm appear to be overwhelmingly indolent and may merit a separate designation.

AIMS: Appendiceal well-differentiated neuroendocrine tumours (NETs) are usually incidental and clinically benign. Several studies have reported different risk factors for nodal metastasis. The aim of this study was to investigate our appendiceal NETs (App-NETs) to determine the factors associated with malignant behaviour. METHODS AND RESULTS: For 120 App-NETs, we reviewed the clinical presentation and follow-up, including serum chromogranin A (CgA) levels, and compiled several microscopic variables. Pathological factors were compared with nodal status and time to biochemical recurrence (elevated serum CgA level) by the use of Cox regression. We also reviewed similar App-NET data in the Surveillance, Epidemiology, and End Results (SEER) Programme. Among our 120 cases, seven patients had positive lymph nodes, and nine developed subsequent elevation of CgA levels; none developed distant metastases or died of disease. Only three patients had grade 2 NETs; none had nodal disease, and one developed an elevated CgA level. Increasing tumour size was associated with an increased risk of nodal disease [odds ratio (OR) 4.99, P = 0.0055). All seven node-positive cases were ≥13 mm. Factors associated with elevated CgA levels included age (OR 1.04, P = 0.041), pT4 disease (OR 10.22, P = 0.033), and nodal disease (OR 24.0, P = 0.012), but not size (OR 2.13, P = 0.072). Of the 1492 reported App-NETs in the SEER database with data on tumour size, 137 (9%) were pN1; only five of these (4%) were coded as being <5 mm. CONCLUSIONS: Small (<5 mm) App-NETs that do not invade the serosa or mesoappendix appear to be overwhelmingly benign and low-grade, requiring neither Ki67 staining nor synoptic reporting. Given their indolent behaviour, different nomenclature or staging may be more appropriate for these NETs.

A Multi-institutional Study of Peritoneal Recurrence Following Resection of Low-grade Appendiceal Mucinous Neoplasms.

BACKGROUND: Peritoneal dissemination of low-grade appendiceal mucinous neoplasms (LAMNs), sometimes referred to as pseudomyxoma peritonei, can result in significant morbidity and mortality. Little is known about the natural history of localized (non-disseminated) LAMNs. OBJECTIVE: The goal of this study was to evaluate the risk of peritoneal recurrence in patients with localized LAMNs. METHODS: We performed a multi-institutional retrospective review of patients with pathologically confirmed localized LAMNs. Baseline characteristics, pathology, and follow-up data were collected. The primary endpoint was the rate of peritoneal recurrence. RESULTS: We identified 217 patients with localized LAMNs. Median age was 59 years (11-95) and 131 (60%) patients were female. Surgical management included appendectomy for 124 (57.1%) patients, appendectomy with partial cecectomy for 26 (12.0%) patients, and colectomy for 67 (30.9%) patients. Pathology revealed perforation in 46 patients (37.7% of 122 patients with perforation status mentioned in the report), extra-appendiceal acellular mucin (EAM) in 49 (22.6%) patients, and extra-appendiceal neoplastic cells (EAC) in 13 (6.0%) patients. Median follow-up was 51.1 months (0-271). Seven (3.2%) patients developed a peritoneal recurrence, with a median time to recurrence of 14.4 months (2.5-47.0). Seven (15.2%) patients with histologic evidence of perforation had recurrence, versus no patients (0%) without perforation (p < 0.001); five (10.2%) patients with EAM versus two (1.2%) patients without EAM (p = 0.007), and one (7.7%) patient with EAC versus six (2.9%) patients without EAC (p = 0.355) had recurrence. CONCLUSIONS: This multi-institutional study represents the largest reported series of patients with localized LAMNs. In the absence of perforation or extra-appendiceal mucin or cells, recurrence was extremely rare; however, patients with any of these pathologic findings require careful follow-up.

An Unusual Case of Acute Appendicitis due to Metastatic Prostatic Adenocarcinoma.

Acute appendicitis is a common surgical emergency in older adults. In the elderly, like in younger cohorts, acute appendicitis most commonly arises without neoplastic underpinnings. However, the occurrence of acute appendicitis in a patient with a concurrent abdominopelvic malignancy should trigger suspicion for the possibility of a metastatic appendiceal neoplasm. We present the case of a 66-year-old man with a background of a biochemically recurrent prostatic adenocarcinoma who presented to the emergency department with acute appendicitis. Histopathologic examination of the resected appendix revealed an unexpected metastatic spread from his prostatic adenocarcinoma.

Clinicopathologic Features of Low-grade Appendiceal Mucinous Neoplasm: A Single-institution Experience of 117 Cases.

Low-grade appendiceal mucinous neoplasm (LAMN) is an enigmatic tumor that lacks the capacity for classic invasion but can dissect through the appendiceal wall, causing pseudomyxoma peritonei (PMP). Most large studies of the histologic spectrum of LAMN and its rate of associated PMP include cases submitted from outside institutions, potentially skewing their findings. We identified 117 cases of LAMN at our institution. Hematoxylin and eosin-stained slides from each were reviewed, and clinical and pathologic parameters were noted. The patients were 76 females and 41 males, with a mean age of 60 years. Presenting symptoms were available for 113 patients; the majority (56%) were symptomatic, typically with abdominal pain. Ninety-one tumors (78%) were grossly dilated, and the entire appendix was submitted in 88 (75%) cases. Median lesion size was 5.5 cm. Ninety-two cases (79%) demonstrated epithelial denudation; these were often markedly dilated and contained intraluminal or mural microcalcifications. Thirty-two (27%) had a mucosal Schwann cell proliferation. On the basis of the American Joint Committee on Staging eighth edition cancer staging manual, of 117 cases, 66% were staged as pTis, 9% as pT3, 24% as pT4a, and 2% as pT4b. Ten cases (9%) were associated with histopathologic evidence of disseminated PMP. Only 1 patient died of disease, while 3 were alive with disease at last follow-up. Previous LAMN studies have utilized both departmental and extradepartmental material; our single-institution review demonstrated lower rates of PMP than some prior studies. Some LAMNs may be markedly dilated with extensive denudation, making the diagnosis difficult to confirm microscopically and ultimately requiring submission of the entire appendix for histologic evaluation.

Along for the Ride: Intrahepatic Cholangiocarcinoma with Concomitant LECT2 Amyloidosis.

We present a case of a 69-year-old Hispanic male with a past medical history of type II diabetes mellitus who presented with a two-month history of abdominal pain. A CT scan was performed which identified a liver mass. Biopsy of the liver mass revealed infiltration of normal liver parenchyma by atypical glands surrounded by pale eosinophilic material. The atypical glands were positive for CK7, while negative for CK20, CDX-2, and TTF-1, consistent with intrahepatic cholangiocarcinoma. A Congo red stain was performed, which highlighted salmon-orange areas, some with a globular appearance, around the glands and within the sinusoids and vasculature. Under polarized light, these areas displayed apple-green birefringence. These findings were consistent with amyloidosis, which was further supported by identification of ALECT2- (leukocyte chemotactic factor-2-) type amyloid on mass spectrometry. To our knowledge, this is the first documented case of intrahepatic cholangiocarcinoma arising in association with LECT2 amyloidosis.

Giant Inflammatory Polyps in Diverticular Disease Mimicking a Colonic Mass: A Potential Malignant Masquerader.

BACKGROUND Inflammatory pseudopolyps (IPPs) are a common manifestation in inflammatory bowel disease (IBD) with more cases reported with ulcerative colitis than Crohn's disease. IPPs can grow to form large polyps which are called giant inflammatory polyps (GIPs). These polyps may cause an obstruction and form a mass-like lesion and surgical resection may be warranted. CASE REPORT A 65-year-old male without a previous history of IBD presented with abdominal discomfort, poor appetite, constipation, weight loss, and hematochezia. Due to the high suspicion of malignancy, a computed tomography (CT) scan was performed and showed a fixed lesion in the mid sigmoid colon highly concerning for a primary colon carcinoma, with scattered diverticula, and associated with elevated carcinoembryonic antigen (CEA). Colonoscopy was done but the scope could not be passed due to obstruction. Sigmoidectomy was performed which showed a huge noninvasive lesion, which looked like pseudopolypoid serpiginous mass as giant inflammatory polyp, with scattered diverticula. On microscopic examination, pathology showed a villous polyp with numerous inflammatory cells, without any dysplasia or carcinoma. CONCLUSIONS GIPs are rarely reported without a history of IBD. Diagnosis of GIPs can be very challenging, and surgery is sometimes indicated for definitive diagnosis.

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.

Mixed Acinar-Endocrine Carcinoma (MAEC) Arising in Duodenal Pancreatic Heterotopia.

Mixed acinar-endocrine carcinoma (MAEC) of the pancreas is a rare neoplasm, consisting of at least 25%-30% of acinar and neuroendocrine populations. Patients are often middle-aged and present with nonspecific symptoms. Imaging typically reveals a solid lesion in the pancreatic head. Management involves surgical resection and the overall prognosis is variable. Here, we present a case of a 48-year-old male who presented with a MAEC arising from duodenal pancreatic heterotopia. This is the one of the first cases, with histologic evidence, of MAEC arising from pancreatic heterotopia.

Effects of subspecialty signout and group consensus on the diagnosis of microscopic colitis.

Microscopic colitis (MC) includes lymphocytic colitis (LC) and collagenous colitis (CC). Microscopic changes are required to establish these diagnoses. While criteria exist, interobserver variability has been reported previously. This has not been evaluated in the context of subspecialty signout (SSSO) or a consensus conference. We identified 133 colon biopsies diagnosed as LC, CC, MC, or normal but with mild changes insufficient for MC. All predated the introduction of SSSO at our institution. They were independently reviewed by three gastrointestinal (GI) pathologists. Cases lacking independent consensus were reviewed by the same pathologists in consensus conference to establish a final diagnosis. Individual diagnoses were compared with the consensus diagnoses, and consensus diagnoses were compared with original diagnoses made by GI and non-GI pathologists. Consensus diagnoses were normal (n = 34), LC (n = 57), and CC (n = 42). "Normal" was the diagnosis most commonly agreed upon independently (27/34 cases, P = 0.0073 versus LC, P = 0.0172 versus CC). The reviewing pathologists independently agreed with 80%, 80%, and 94% of consensus diagnoses (κ = 0.70, 0.69, and 0.91). The group consensus agreed with the diagnoses in 49 of 58 (84%) cases originally signed out by non-GI pathologists (κ = 0.77) and in 44 of 57 (77%) cases originally signed out by GI pathologists (κ = 0.63). Good interobserver agreement exists for MC, though whether GI subspecialty training improves agreement remains unclear. Group consensus may aid in diagnosis of difficult/borderline MC cases.