Association of IgG4 response and autoimmune pancreatitis with intraductal papillary-mucinous neoplasms

Objectives: Concurrent intraductal papillary-mucinous neoplasm (IPMN) and autoimmune pancreatitis (AIP) was observed in a patient (index case) at our institution. Cases of coincidental IPMN and type 1 AIP and concurrent ductal adenocarcinoma (PDAC) and AIP have been previously reported. In this study we evaluate the hypothesis that IPMN elicits an IgG4 response. Methods: Twenty-one pancreases (including the index case) with IPMN resected at our institution were studied. H&E stained slides were reviewed and blocks of peritumoral pancreas were immunostained with IgG4 to look for IgG4-positive plasma cells. Results: We found evidence of variable IgG4 overexpression in 4/21 (19%) of IPMN. These included the index case and three others without stigmata of AIP. Conclusion: A small subset of pancreatic neoplasms including intraductal papillary-mucinous neoplasms (IPMN) is associated with an IgG4 autoimmune response that sometimes progresses to peritumoral type 1 AIP and less often to diffuse AIP and IgG4-related systemic disease

Lymphocytic Esophagitis in Nonachalasia Primary Esophageal Motility Disorders: Improved Criteria, Prevalence, Strength of Association, and Natural History.

Lymphocytic esophagitis (LE) is a histologic pattern with no established clinical correlates in the majority of patients. The goal of this study was to evaluate the association between nonachalasia primary esophageal motility disorders (PEMD) and LE. Sixty-nine patients with PEMD and esophageal biopsies, including 22 with nutcracker esophagus, 33 with ineffective motility, and 14 with diffuse spasm, constituted the study group. The control group consisted of 70 patients with severe dysmotility-negative gastroesophageal reflux disease requiring referral for Nissen fundoplication. To improve the criteria for LE, a lymphocyte reference range at different esophageal levels was first established in 17 healthy volunteers. The cutoffs for normal intraepithelial lymphocytes, defined as lymphocyte levels not exceeding mean level±2 SDs, were set at 62, 46, and 41 lymphocytes per high-power field at 0 to 2, 5, and 10 cm above the gastroesophageal junction, respectively. Predominantly focal peripapillary LE was observed in approximately 40% of patients with nutcracker esophagus or diffuse spasm and in 20% of patients with ineffective motility, in comparison with 4% of patients with dysmotility-negative gastroesophageal reflux disease (P<0.035 vs. any subtype of PEMD). Overall, LE was strongly associated with PEMD in multivariate analysis (adjusted odds ratio, 7.93; 95% confidence interval, 2.26-27.9; P=0.001). LE had a chronic course in 56% of the patients with follow-up biopsies. In conclusion, LE has a strong association with PEMD, suggesting the utility of LE in raising the possibility of PEMD

The microscopic anatomy of the esophagus including the individual layers, specialized tissues, and unique components and their responses to injury

The esophagus, a straight tube that connects the pharynx to the stomach, has the complex architecture common to the rest of the gastrointestinal tract with special differences that relate to its function as a conduit of ingested substances. For instance, it has submucosal glands that are unique and have a specific protective function. It has a squamous lining that exists nowhere else in the gut except the anus and it has a different submucosal nerve plexus when compared to the stomach and intestines. All of the layers of the esophageal wall and the specialized structures including blood and lymphatic vessels and nerves have specific responses to injury. The esophagus also has unique features such as patches of gastric mucosa called inlet patches at the very proximal part and it has a special sphincter mechanism at the most distal aspect. This review covers the normal microscopic anatomy of the esophagus and the patterns of reaction to stress and injury of each layer and each special structure.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147079/1/nyas13705_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147079/2/nyas13705.pd

Atypical lipomatous tumor mimicking giant fibrovascular polyp of the esophagus: report of a case and a critical review of literature

An 81-year-old man presented to the emergency department with a mass protruding from his mouth after an episode of emesis. A computed tomography scan showed a hypodense, polypoid structure with a fatty component. The long polyp was attached by a narrow stalk to the cervical esophagus. A 14.0-cm slender mass resembling a giant fibrovascular polyp (GFP) of the esophagus was resected. The microscopic, immunohistochemical, and molecular findings were, however, those of an atypical lipomatous tumor (ALT). Atypical lipomatous tumor of the esophagus is a rare, low-grade malignant neoplasm, with a potential for local recurrence and, in most instances, presents as a large intraluminal polyp mimicking a GFP. Cases reported in the literature as primary myxoid liposarcomas of the esophagus are in all likelihood examples of ALT with myxoid change. A recent case reported as a GFP with karyotypic abnormalities on comparative genomic hybridization is also most likely to be an ALT mimicking a GFP. Pathologists need to be aware of the pitfalls in the diagnosis of ALT of the esophagus and should carefully evaluate the adipocytic component of these lesions

Apolipoprotein D in CD34-positive and CD34-negative cutaneous neoplasms: a useful marker in differentiating superficial acral fibromyxoma from dermatofibrosarcoma protuberans

More recent techniques to characterize the genetic profile of soft-tissue tumors include the use of gene arrays. Using this technique, Apolipoprotein D (Apo D), a 33-kDa glycoprotein component of high-density lipoprotein, has been found to be highly expressed in dermatofibrosarcoma protuberans. To corroborate these results, we sought to ascertain the utility of Apo D by investigating its sensitivity and specificity in a variety of CD34-positive and CD34-negative cutaneous neoplasms including superficial acral fibromyxoma, sclerotic fibromas, and cellular dermatofibromas. Of interest, we found absence of Apo D expression in all four cases of superficial acral fibromyxoma. Of the remaining CD34-positive lesions, Apo D expression was noted in 35/36 (97%) cases of dermatofibrosarcoma protuberans, 3/5 (60%) giant-cell fibroblastomas, 4/4 (100%) sclerotic fibromas, 8/8 (100%) neurofibromas, and 1/1 (100%) solitary fibrous tumor. Of the CD34-negative lesions, Apo D expression was noted in 2/22 (9%) regular dermatofibroma, 23/45 (51%) cellular dermatofibroma, 10/10 (100%) malignant fibrous histiocytoma, 9/10 (90%) atypical fibroxanthoma, 7/8 (86%) cellular neurothekeoma, 9/9 (100%) malignant melanoma, 8/8 (100%) melanocytic nevi (100%), 0/2 superficial angiomyxoma, 0/15 fibromatosis, 0/1 nodular fasciitis, and 1/2 (50%) desmoplastic fibroblastomas. In summary, our findings indicate that Apo D expression is not specific to dermatofibrosarcoma protuberans. Its principal use as an immunohistochemical adjunct lies in its utility in differentiating superficial acral fibromyxoma from dermatofibrosarcoma protuberans. Although strong positive staining of Apo D in a markedly atypical fibrohistiocytic lesion is suggestive of atypical fibroxanthoma and/or malignant fibrous histiocytoma, further studies with the inclusion of other atypical spindled cell neoplasms are required to conclusively prove the same

Fine needle aspiration of an intranodal follicular dendritic cell sarcoma: A case report with molecular analysis and review of the literature

Follicular dendritic cell sarcoma (FDCS) is a rare malignant neoplasm of follicular dendritic cell origin which can present a diagnostic challenge. Due to the rarity of this neoplasm, its molecular pathogenesis has not been fully elaborated. A previous series of 13 cases reported that 38% contained mutations of genes encoding proteins involved in negative regulation of NF-κB. NF-κB is a family of transcription factors regulated through multiple cellular processes known as the canonical and noncanonical pathways. Here we present the case of a 62-year-old man who presented with abdominal pain and systemic symptoms and was found to have a mass in the porta hepatis. Fine needle aspiration cytology demonstrated a spindle cell neoplasm with vesicular chromatin and prominent nucleoli with admixed lymphocytes. Surgical resection showed an intranodal, 7.3 × 5.5 × 3.5 cm, solid mass composed of plump, spindle to histiocytoid cells with ovoid nuclei and small, prominent nucleoli arranged in a whorled and fascicular pattern. The lesional cells stained positively for CD21, CD23, and CD35 by immunohistochemistry, consistent with a diagnosis of FDCS. Next-generation sequencing revealed pathologic mutations in three genes involved in NF-κB regulation pathways: NFKBIA, TNFAIP3, and TRAF3. A pathologic TP53 mutation was also identified. This case report supports prior associations of the NF-κB pathway dysregulation and FDCS. Additionally, it is the first reported FDCS case with TRAF3 mutation as well as the first reported case to suggest disruption in both the canonical and noncanonical NF-κB pathways in the same lesion