Acinar dysplasia (AcDys) of the lung is a rare lethal developmental disorder in neonates characterized by severe respiratory failure and pulmonary arterial hypertension refractory to treatment. Recently, abnormalities of TBX4-FGF10-FGFR2-TMEM100 signaling regulating lung development have been reported in patients with AcDys due to heterozygous single-nucleotide variants or copy-number variant deletions involving TBX4, FGF10, or FGFR2. Here, we describe a female neonate who died at 4 hours of life due to severe respiratory distress related to AcDys diagnosed by postmortem histopathologic evaluation. Genomic analyses revealed a novel deleterious heterozygous missense variant c.728A>C (p.Asn243Thr) in TBX4 that arose de novo on paternal chromosome 17. We also identified 6 candidate hypomorphic rare variants in the TBX4 enhancer in trans to TBX4 coding variant. Gene expression analyses of proband\'s lung tissue showed a significant reduction of TMEM100 expression with near absence of TMEM100 within the endothelium of arteries and capillaries by immunohistochemistry. These results support the pathogenicity of the detected TBX4 variant and provide further evidence that disrupted signaling between TBX4 and TMEM100 may contribute to severe lung phenotypes in humans, including AcDys.

Lipase hypersecretion syndrome (LHS) is a rare paraneoplastic syndrome, associated with acinar cell carcinoma of the pancreas (ACCP) in 10% to 15% of patients. Clinically, LHS manifests itself with the appearance of subcutaneous fibrocystic nodules, associated with trophic changes in the overlying skin, such as ulcers or fistulas that are difficult to manage, mainly affecting the lower extremities. Additionally, lipolysis near the joints and in the intraosseous adipose tissue can cause bilateral arthralgias, especially of the knees and ankles. We report a 57-year-old man, with a history of insulin resistance and allergic rhinitis, who presented in June 2019 with multiple subcutaneous nodules in the lower extremities, predominantly in both ankles, associated with arthralgia in that region. Additionally, a CT scan of the abdomen revealed a significant abdominal mass, measuring approximately 17 cm and in contact with the body and tail of the pancreas, pathologically compatible with an ACCP. Treatment with capecitabine was started with a favorable progression. The patient currently presents a small left lateral retro malleolar fistula, which, given the analyzes, studies and reviewed literature is concluded to be a lesion in the context of LHS.

Amphicrine carcinomas are epithelial neoplasms composed of cells with co-existing exocrine-neuroendocrine phenotype and are challenging lesions from both diagnostic and therapeutic perspectives.Here, we report the case of a 63-year-old male patient with a gastric nodule that was endoscopically biopsied, revealing histological features of a type 3 well-differentiated gastric neuroendocrine tumor (NET). At imaging, the lesion was single and limited to the stomach, but did not present In-111Octreotide uptake, despite SSTR2A immunohistochemical expression. The patient underwent a wedge resection of the gastric wall, with a final pathological diagnosis of amphicrine carcinoma with pancreatic acinar cell and neuroendocrine features (pT1b). Predictive immunohistochemistry showed microsatellite stability and negative HER2 status. Hotspot targeted deep sequencing of 57 genes showed no somatic mutation, in agreement with the low mutational burden reported for gastric amphicrine carcinomas. Due to a low stage of the tumor and the poor performance status of the patient, no additional oncological treatment was administered. The patient was disease-free after 18 months.This unusual case highlights the importance of considering amphicrine carcinoma in the diagnostic work-up of gastric type 3 NET. This can be done by including in the immunohistochemical panel non-neuroendocrine markers, such as the pancreatic acinar cell and glandular ones. Correct pathological diagnosis is pivotal to determine the appropriate staging (NET vs exocrine one) for surgical and oncological management.

BACKGROUND: Pancreatic panniculitis is characterized by subcutaneous fat necrosis and is a rare presentation of an underlying pancreatic disease, appearing in approximately 2-3% of all patients with a pancreatic disease. The nodules usually involve the lower extremities. Pancreatic panniculitis is commonly associated with acute or chronic pancreatitis, and occasionally with pancreatic cancer, especially acinar cell carcinoma.
METHODS: A 77-year-old Caucasian woman with no significant medical history was referred to our center with multiple painful, itchy, and warm red/blue cutaneous nodules on the left lower leg. These skin lesions were consistent with the clinical diagnosis of panniculitis. The skin biopsy obtained showed a predominantly lobular panniculitis with fat necrosis of which the aspect was highly suspicious for pancreatic panniculitis. Further analysis revealed high lipase serum of > 3000 U/L (normal range < 60 U/L), and on computed tomography scan a mass located between the stomach and the left pancreas was seen. Endoscopic ultrasonography-guided fine-needle biopsy confirmed the diagnosis of acinar cell carcinoma. After discussing the patient in the pancreatobiliary multidisciplinary team meeting, laparoscopic distal pancreatectomy including splenectomy and en bloc wedge resection of the stomach due to tumor in-growth was performed. The cutaneous nodules on both legs disappeared 1-2 days after surgery. No long-term complications were reported during follow-up. One year after surgery, the patient presented with similar symptoms as preoperatively. Computed tomography scan showed local recurrence and distal metastases, which were subsequently confirmed by biopsy. She started with palliative folinic acid-fluorouracil-irinotecan-oxaliplatin chemotherapy but stopped after two cycles because of disease progression. The patient died 2 months later, 13 months after surgical resection.
CONCLUSIONS: This case illustrates the importance of clinically recognizing cutaneous nodules and pathological recognizing the specific microscopic changes as sign of a (malignant) pancreatic disease.

Acinar cystic transformation (ACT) is a rare cystic lesion of the pancreas lately reclassified as a non-neoplastic entity. This is a presentation of a case of ACT and a review of the literature. A systematic PubMed search was conducted, yielding a result of 24 publications. Including our case report, 75 cases of ACT have been reported in the literature. The patients are mainly females with initial symptoms of abdominal pain. The cysts are primarily located in the head of the pancreas and are often multilocular on cross section and have a mean size of 53.2 mm. Microscopically, the cysts are lined by an acinar epithelium with abortive acinar formations. The cells are immunohistochemically positive in stains for trypsin, chymotrypsin and CK7. The Ki67-index is low; 1-2 %. No genetic alterations indicative of a neoplastic pathogenesis have been found. The mean follow up time is 37.4 months and no malignant transformation has been observed. A preoperative diagnosis is difficult to establish, but microbiopsies seem a promising tool. The indication for surgical intervention should be founded on the symptoms of the patients since no malignant transformation has ever been reported.

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Pancreatic neuroendocrine neoplasia is categorized by grade, size, and functional status. Neuroendocrine microadenoma (NEMA) is defined as a neuroendocrine tumor (NET) that measures less than 0.5 cm in diameter. Multiple NEMAs are termed neuroendocrine adenomatosis (NEMAtosis). The surgical pathology and clinical aspects of pancreatic NEMAtosis have been reported, but there has been no report regarding EUS-FNA cytology of NEMAtosis. We report a case of NEMAtosis with cytologic correlation and illustrate the diagnostic challenges and potential pitfalls. The pre-operative cytology can be problematic. The main differential diagnosis of the EUS-FNA specimen includes NET, normal pancreas, and islet cell hyperplasia/aggregation associated with chronic pancreatitis. The helpful cytopathologic feature of NEMAtosis is the presence of two intermingled populations of loosely-cohesive neuroendocrine cell clusters and tight acinar cell groups arranged in microacinar and/or grape-like structures. Although neuroendocrine cells and acinar cells possess different cytomorphology, the distinction is not always straightforward because both types of cells are small and cytologically bland. Cytologic assessment of both architecture and individual cell morphology is imperative to avoid interpretation error and further guide appropriate clinical management. Diagn. Cytopathol. 2017;45:143-147. © 2016 Wiley Periodicals, Inc.

A case of combined micropapillary and plasmacytoid urothelial carcinoma (UC) of the urinary bladder is presented for a 74-year-old male who was admitted to the hospital with gross hematuria and multifocal papillary bladder tumors. Abdominal computed tomography showed a large enhancing mass on the left lateral and anterior wall of the urinary bladder, which was highly suspicious for extravesicular extension and focal extension of the anterior lesion to the pubic bone. In voided urine, cancer cells were scattered as micropapillae or nests as well as single cells on the low power view. On a higher power view, micropapillae or nests were composed of pleomorphic, high grade tumor cells with an inverted nuclear arrangement and with acinar structures occasionally identified. Single cells were discohesive and large with a thick cytoplasm and eccentrically located nuclei. Histologically, the tumor from the resected bladder showed diffusely infiltrating micropapillae or nests with a surrounding halo and dense singly-scattered plasmacytoid cells. Immunohistochemically, the cancer cells were positive for cytokeratin-7 and cytokeratin-20 but negative for S-100, leukocyte common antigen, and vimentin. At the time of radical cystectomy, severe adhesions and peritoneal metastases were found and the surgery was discontinued. The patient received systemic chemotherapy, but died of bladder cancer 14 months after surgery.

We report an atypical case of non-sebaceous lymphadenoma (NSL) of the parotid gland showing serous acinic cell differentiation. NSL is a rare benign salivary gland tumor with intermingled lymphoid and epithelial tissues without sebaceous differentiation. Since the first description of a case designated by Auclair et al. as \'non-sebaceous lymphadenoma\' in 1991, to our best knowledge, only 37 cases have been reported, and no differentiation of tumor cells into serous acinic cell lineage has been described so far. In this paper, we present a case of NSL with serous acinic cell differentiation. The patient was a 78-year-old female with the complaint of a painless mass in the left parotid gland. The surgically resected tumor was encapsulated and measured 13 × 9 × 9 mm. Histologically, the tumor had the features of NSL, and an unusual finding of this case was the presence of epithelial cells with serous acinic cell differentiation. Dense cytoplasm packed with basophilic granules in those cells was positive in periodic acid Schiff reaction after diastase digestion (D-PAS), which was compatible with the feature of serous acinic cell differentiation. Possible differentiation of the epithelial component into serous acinic cell in this rare entity is warranted to avoid confusion in the diagnosis.

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