Intracellular Mucin Research Articles

Mucin-producing papillary thyroidal carcinoma with unusual histology: A rare case report

Background: Although mucinous carcinoma or mucoepidermoid carcinoma of the thyroid gland are an extremely rare but an established entity, papillary thyroidal carcinoma (PTC) with mucin production is also exceedingly rare. Case report: We reported one rare case of mucin producing PTC with unusual histology. The patient was 71 years-old Japanese man. The hemi-thyroidectomy was performed. Histologically, the tumor cells harbored the similar features with conventional PTC, but this case indicated extracellular and intracellular mucin. On the other hand, the tumor showed cystic-papillary or cribriform growth of the columnar tumor cells. Conclusions: We diagnosed it as mucin-producing PTC with columnar cell variant (CCV). We examined it immunohistochemically, and this case expressed TTF-1, thyroglobulin, and cytokeratin (CK)7, but was negative for HBME-1. We discuss on the differential diagnosis.

Amphicrine carcinoma of the stomach and intestine: a clinicopathologic and pan-cancer transcriptome analysis of a distinct entity

Background and aimAmphicrine carcinoma, in which endocrine and epithelial cell constituents are present within the same cell, is very rare. This study characterized the clinicopathologic and survival analysis of this tumor, further compared the genetic diversities among amphicrine carcinoma and other tumors.Materials and methodsThe clinicopathologic characteristics and survival outcomes of amphicrine carcinoma in this study were analyzed. The pan-cancer transcriptome assay was utilized to compare the genetic expression profile of this entity with that of conventional adenocarcinoma or neuroendocrine tumors.ResultsTen cases (all in male patients) were identified in the stomach or intestine, with a median patient age of 62 years. There were characteristic patterns in the tumors: tubular, fusion or single-file growth of goblet- or signet ring-like cells. Four tumors were classified as low-grade and 6 as high-grade according to the histologic architecture. All cases were positive for neuroendocrine markers (synaptophysin and chromogranin A) and showed intracellular mucin in the amphicrine components. Four cases exhibited mRNA expression patterns showing transcriptional homogeneity with conventional adenocarcinomas and genetic diversity from neuroendocrine tumors. During the follow-up period, 3 patients died of disease, all of whom had high-grade tumors. Patients with high-grade amphicrine carcinoma had worse outcomes than those with low-grade tumors.ConclusionsThis study confirms the morphological, immunostaining and transcriptome alterations in amphicrine carcinoma distinct from those in conventional adenocarcinomas and neuroendocrine tumors, but additional studies are warranted to determine the biological behavior and therapeutic response.

Invasive breast lobular carcinoma with extracellular mucin: a clinicopathological analysis

Objective: To study the clinicopathological features of invasive lobular carcinoma (ILC) of the breast with extracellular mucin and outcomes of patients. Method: Clinicopathological features and clinical follow-up (39-123 months and a median follow-up of 55 months) of seven ILC with extracellular mucin were obtained. Hematoxylin-and-eosin (H&E) and immunohistochemistry (IHC) stained sections were reviewed, and fluorescence in situ hybridization (FISH) assay was performed for tumors with HER2 IHC 2+. Patient prognosis was analyzed and literatures related to ILC with extracellular mucin were reviewed. Results: All seven patients were female, aged from 43 to 73 years (median age, 55 years). The tumors ranged in size from 1 to 5 cm (median size 2 cm). All seven cases were of histological grade 2. Most areas of the tumors presented with the morphology of classic ILC, and variable amount of extracellular mucin were observed focally. In six cases, part of the tumor cells contained intracellular mucin, and the nucleus were pushed to one side of the cells, creating the impression of signet-ring cells. Two patients had lymph node metastases at diagnosis, and developed liver and bone metastases at 38th and 48th month, respectively, after surgery, and died at 48th and 123th month, respectively. While the other five patients, except one lost to follow-up, had been disease-free during the follow-up period. IHC results showed estrogen receptor (ER) and progesterone receptor (PR) positivity in 7/7 and 6/7 cases, respectively. Tumors of six patients were HER2 IHC 0/1+. The remaining one was HER2 IHC 2+, while FISH assay revealed HER2 gene amplification in that tumor. The proportion of cases with HER2-positivity was 1/7. The proliferation index Ki-67 ranged from less than 5% to 30%, and Ki-67 less than or equal to 10% were in 5/7 cases. According to the 2013 St. Gallen International Expert Consensus on breast cancer, all tumors were of luminal types; of those, two were luminal A and five were luminal B. Conclusions: ILC with extracellular mucin tends to occur in women over 50 years old. All tumors in the study are grade 2 classic ILC, with signet-ring cells as a common feature. All seven tumors are classified as luminal types, with luminal B as the main molecular subtype.

SMARCB1 (INI-1)-Deficient Adenocarcinoma of the Sinonasal Tract: A Potentially Under-Recognized form of Sinonasal Adenocarcinoma with Occasional Yolk Sac Tumor-Like Features

The classification of sinonasal adenocarcinoma (SNAC) is complex. The high-grade, non-intestinal SNAC group is particularly heterogeneous, with tumors showing widely variable morphology. SMARCB1 (INI-1)-deficient sinonasal carcinoma is a newly described, aggressive tumor that usually resembles sinonasal undifferentiated carcinoma (SNUC) or non-keratinizing squamous cell carcinoma; however, glandular differentiation has been rarely reported and this feature may be under-recognized. We present a dedicated series of 12 SMARCB1-deficient SNACs. All tumors had an oncocytoid/plasmacytoid cytomorphology with variable degrees of glandular differentiation consisting of tubules and cribriform structures with foci of intracellular or intraluminal mucin. Three of 12 tumors exhibited foci of yolk sac tumor-like histologic features. The tumors were uniformly high-grade, with nuclear pleomorphism, elevated mitotic rates and frequent necrosis. By immunohistochemistry, all tumors were entirely SMARCB1-deficient, and 10 of 12 were CK7-positive. Occasional expression of CDX2 (4 of 12), CK20 (3 of 12), and p40 (3 of 10) was seen. Expression of yolk sac markers was variably present in tumors that harbored yolk sac-like areas but also tumors that did not: glypican-3 (10 of 11), SALL4 (6 of 11), HepPar-1 (4 of 11), PLAP (1 of 10), and AFP (1 of 11). SMARCB1-deficient sinonasal carcinoma, particularly the oncocytoid/plasmacytoid form, can demonstrate variable degrees of glandular differentiation. This unexpected morphology combined with variable immunohistochemical results may lead to misdiagnoses of high-grade intestinal or non-intestinal SNAC, myoepithelial carcinoma, or even yolk sac tumor or metastatic hepatocellular carcinoma.

Intracellular Processing of Human Secreted Polymeric Airway Mucins.

Mucociliary clearance is a crucial component of innate defense of the lung. In respiratory diseases, such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis, mucus with abnormal properties contributes to obstruction of the airways. The failure in function of mucus in airway clearance and pathogen protection leads to chronic infection and risk of death. Polymeric mucins (MUC5AC and MUC5B) provide the structural framework of the airway mucus gel. The intracellular synthesis and assembly of these enormous, polymeric O-linked glycoproteins is a complex, multistage process involving intra- and intermolecular disulfide bond formation and extensive addition of O-glycan chains. The fully formed polymers are packaged in a highly organized and condensed form within secretory granules inside specialized secretory cells, and after the appropriate stimulus, mucins are released and expand to form mucus. This short article brings together the current knowledge on the different steps in the production of mucin polymers and the molecular mechanisms that condense them into a packaged form in secretory granules. It is by unraveling the molecular mechanisms that control intracellular mucin supramolecular structure that we might gain new insight into what determines mucus gel properties in health and disease.

A Tumor with Two Faces

According to the most recent WHO classification of digestive tumors, mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is a rare neoplasm of the gastrointestinal tract composed of exocrine and neuroendocrine components, where each component represents at least 30% of the lesion. Previously referred to as MANEC, these tumors have been renamed multiple times since their initial discovery. A 68-year-old man without significant PMH, presented with a 1-month history of 6-8 episodes per day of watery non-bloody bowel movements associated with spasmodic abdominal discomfort and 12-pound weight loss. A routine screening colonoscopy one year previously had noted only benign polyps. A CT abdomen/pelvis showed a circumferential mass localized in the ascending colon (Fig. 1). Colonoscopy showed a large exophytic mass at the proximal hepatic flexure, with biopsies showing adenocarcinoma with neuroendocrine features. PET/CT for staging did not show any distant metastasis (Fig. 2). Pathology from a laparoscopic right hemicolectomy showed a tumor invading through the muscularis propria into the pericolonic adipose tissue (T3) with negative margins or evidence of lymph node involvement (N0), however there was evidence of lymphovascular and perineural invasion (stage II). Cytopathology showed a high grade, well to moderately differentiated neuroendocrine carcinoma comprising 60% of the tumor and also poorly differentiated adenocarcinoma with signet ring features comprising 30% of the tumor (Fig. 3). The patient has started adjuvant carboplatin and etoposide to lower the risk of recurrent disease from high grade neuroendocrine carcinoma.1622_A Figure 1. CT abdomen/pelvis with contrast: Circumferential mass at the distal ascending colon/hepatic flexure measuring at least 38 mm and with extraluminal extension versus contiguity with lymph nodes1622_B Figure 2. PET scan showing an intense hyper metabolic mass in the ascending colon and hepatic flexure, without evidence of distant metastasis.1622_C Figure 3. Fig 3. Hematoxylin and eosin stained sections showing a high-grade malignant neoplasm with both neuroendocrine (Panel A) and poorly differentiated adenocarcinoma (Panel B) with each component being at least 30% of the tumor. The neuroendocrine nature in Panel A is confirmed by diffuse positivity for synaptophysin (Panel C) and focal positivity for chromogranin. The adenocarcinoma component in Panel B shows signet ring cells and extracellular and intracellular mucin. The intracellular mucin is confirmed by mucicarmine (Panel D) and AB/PAS stains. Both components were positive for pancytokeratin. Ki67 markers confirmed a high proliferative rate (Panel E). These findings are diagnostic of mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN)MiNEN is a rare GI tumor that has only been described in case series or case reports and currently has an unknown incidence. Specialized immunostains are required to make the diagnosis, including chromogranin, synaptophysin, CD56 and NSE, along with non-endocrine markers such as keratin 7 and 20, CDX2 and CEA. The mean age of diagnosis is 60 years and is generally associated with a poor prognosis, with 67% of patients presenting with metastatic disease at the time of diagnosis. The 5-year survival rate ranges from 50% to 65.5%. Currently due to the rarity of these tumors, there are no established guidelines for treatment, but anecdotal therapies include surgical resection for localized disease and chemotherapy for advanced disease.

Pulmonary Carcinomas With Mucinous and Neuroendocrine Differentiation: Expanding the Spectrum of Amphicrine Carcinomas.

Amphicrine carcinoma is a distinct type of carcinoma characterized by synchronous exocrine and endocrine differentiation within the same tumor cell. Such tumors are exceedingly rare and most commonly recognized in the gastrointestinal tract. In the lung, sporadic descriptions of such lesions exist. This report presents 3 more such tumors, expanding the spectrum of amphicrine carcinomas in this organ. The patients were 3 men, 53 to 78 years of age (mean: 63 y) and all were current or former smokers. In one patient the tumor was an incidental finding, the others presented with lower respiratory symptoms. Microscopically, the lesions had an organoid pattern, consisting of nests of large tumor cells with peripheral palisading, vesicular nuclei and prominent nucleoli reminiscent of large cell neuroendocrine carcinoma. In addition, the tumor nests also showed glandular features, characterized by gland-like lumina filled with mucin and intracytoplasmic mucin droplets. Immunohistochemical studies showed diffuse reactivity of the tumor cells with synaptophysin and chromogranin and variable reactivity with TTF-1. Mucin stains highlighted extracellular and intracellular mucin deposition. Clinical follow-up demonstrated that one patient had died of his disease 12 months after surgery while another was alive and free of disease 21 months after surgery. The third patient was alive with widespread metastatic disease 8 months after diagnosis. This series highlights a rare variant of pulmonary carcinoma showing synchronous exocrine and endocrine differentiation. Recognition of this type of tumor is important in terms of tumor classification and to identify an entity with potential aggressive behavior.

Periampullary neuroendocrine tumor with large intracellular mucin globules, an amphicrine tumor?

Amphicrine carcinoma is a rare type of mixed adenoneuroendocrine carcinoma in which both exocrine and endocrine components are co-expressed in the same tumor cells. We report a case of a 57 year old man with a complex cystic and solid periampullary mass which shows a misleading poorly differentiated morphology. The tumor cells are positive for neuroendocrine markers with some cells showing large intracytoplasmic mucin. Additionally, CEA immunostain is weakly, but diffusely positive in the same tumor cells. The tumor may represent an amphicrine carcinoma, however, it has been reported that neuroendocrine cells may show aberrant mucin production. To what extent of mucin production should the tumor have to be considered as amphicrine is the question without answer, and currently the diagnostic criteria for amphicrine carcinoma have not been well established.

A Highly Sensitive Fluorogenic Probe for Imaging Glycoproteins and Mucine Activity in Live Cells in the Near-Infrared Region.

A novel fluorescent molecular probe is reported, which is able to detect glycoproteins, especially mucins, with high sensitivity and with a turn-on response along with a large Stokes shift (>130 nm), within the biologically active window. The probe contains an aminotricarbocyanine as the fluorescent reporter with a linked benzoboroxole as the recognition unit, which operates through a dynamic covalent reaction between the boronic hemiester residue of the receptor and cis-diols of the analyte. The superior selectivity of the probe is displayed by the labeling of mucins present in Calu-3 cells. The new benzoboroxole fluorescent derivative gathers together key properties to make it a highly rated molecular probe: specificity, excellent solubility in water, and off-on near infrared emission. This probe is expected to be an excellent tool for imaging intracellular mucin to evaluate mucus-related diseases as well as a sensing strategy towards glycosylated structures with a high potential for theranostics approaches in biological samples.

Primary breast carcinomas with neuroendocrine features: Clinicopathological features and analysis of tumor growth patterns in 36 cases.

Primary breast carcinoma with neuroendocrine features (NEBC) is an uncommon tumor. In the classification of WHO 2012, these tumors were categorized as: 1- neuroendocrine tumor, well-differentiated; 2- neuroendocrine carcinoma, poorly differentiated/small cell carcinoma; and 3- invasive breast carcinoma with neuroendocrine differentiation. In this study, we reviewed NEBC except poorly differentiated/small cell carcinoma variant in order to define the morphological growth patterns and cytonuclear details of these tumors. All breast surgical excision materials between 2007 and 2016 were re-evaluated in terms of neuroendocrine differentiation. Thirty-six cases showing positive staining for synaptophysin and/or chromogranin A in ≥50% of tumor cells were included in the study. All cases were female with a mean age of 67.4. Mean tumor diameter was 26 mm. Multifocality was noted in 5 cases. Grossly, they were mostly infiltrative mass lesions. T stages, identified in 34 cases, were as follows: 13 cases with pT1; 19 pT2 and 2 pT3. We described schematically 4 types of patterns depending on predominant growth pattern, except one case: 1) Large-sized solid cohesive groups (6 cases), 2) Small- to medium-sized solid cohesive groups with trabeculae/ribbons and glandular structures (6 cases), 3) Mixed growth patterns (20 cases), 4) Invasive tumor with prominent extracellular and/or intracellular mucin (3 cases). The tumor cells were mostly polygonal-oval with eosinophilic/eosinophilic-granular cytoplasm. The nuclei of tumor cells were mostly round to oval with evenly distributed chromatin. Only 5 cases showed high grade nuclear and histological features. Molecular subtypes of the cases were as follows: 33 luminal A, 2 luminal B, and 1 triple negative. NEBC should come to mind when a tumor display one of the morphological patterns described above, composed of monotonous cells with mild to moderate nuclear pleomorphism and abundant eosinophilic/eosinophilic granular or clear cytoplasm, especially in elderly patients.

Significance of mucin stains in the diagnosis of carcinoma of cervix

Background: As many as 25-35% of carcinoma cervix without clearly defined glandular structure on histopathological examination by Hematoxylin and Eosin stains have intracellular mucin demonstrable by using mucin stains which may redefine the classification of cervical carcinomas which becomes important as mucus secreting neoplasms resembling pure squamous cell carcinomas are more aggressive and have worse prognosis than their purely squamous counterparts.Methods: Our study conducted at Assam Medical College Dibrugarh for a period of one year. 54 cases of carcinoma cervix diagnosed on Hematoxylin and Eosin stain were subjected to mucin stains i.e. Periodic acid Schiff and Alcian blue at pH 2.5 and the results were compared with each other.Result: Out of the total 54 cases, 47 cases were squamous cell carcinoma(SCC,87.03%) which were further graded as well differentiated type(12/47)SCC, moderately differentiated(31/47)SCC, poorly differentiated(4/47)SCC and only 3 cases were adenosquamous carcinoma( 3/54; 5.5%) and adenocarcinoma( 4/54; 7.41%) by conventional H& E stain. On subjecting to specific mucin stains, however 21.2% (10 cases)of the SCC(47 cases) contained intracellular mucin with varying percentage, along with adenocarcinoma and adenosquamous carcinomas . Revised diagnosis after application of mucins stains showed pure squamous cell carcinomas (37/54) i.e. 68.51%, adenocarcinomas remained same at 7.41% (4/54) and adenosquamous carcinoma increased(13/54) to 24.07%.Conclusion: Identifying adenosquamous carcinomas after application of mucin stains which were not detectable by H&E stained sections has sparked academic interest because of its prognostic significance as it has been found in various studies that adenosquamous carcinomas often pursue an aggressive course and are associated with worse prognosis than their pure adeno- and squamous – counterparts as most of them are poorly differentiated. So recognition of this type of carcinomas can help to predict prognosis and to plan management.DOI:10.21276/APALM.1583

Structural and functional rearrangement of the large intestine after first stage of the reconstructive and restore operations

The morphological changes of the large bowel mucous membrane of the patients after reconstructive and restore operations (RRO) were analyzed. The progressive reduction of the colon mucosa columnar epithelial cells with their replacement by monolayer of the goblet cells that secrete mainly sialomucins during the six-month follow-up was established. Recovery of the proximal colon mucosa with decrease of hyperplastic and reactive inflammatory changes, stabilization of intracellular mucin secretion by goblet cells in the proximal part, the low degree of atrophy and fibrosis in the distal part of colon mucosa were observed after the third month, indicating the most favorable time for RRO.

Cytological features in eight patients with ALK‐rearranged lung cancer

ALK-rearranged lung cancer has been recently identified. Although signet-ring cell morphology and mucinous cribriform pattern are considered to be characteristic of ALK-rearranged lung cancer. Some studies have also suggested cytological features. This study investigated cytological features of ALK-rearranged lung cancer in eight patients. Cytologically, the tumor cell group varied from isolated to large clusters. Small nucleoli, fine granular to vesicular chromatin, and nuclear groove were observed in all patients. Furthermore, extracellular and intracellular mucin and signet-ring cells were identified in five patients. This study demonstrated that the presence of extracellular and intracellular mucin, signet-ring cells, small nucleoli, fine granular to vesicular chromatin, and nuclear groove in cytological samples may be a diagnostic clue for ALK-rearranged lung cancer.

Pancreatic intraductal tubulopapillary neoplasm is genetically distinct from intraductal papillary mucinous neoplasm and ductal adenocarcinoma

Intraductal tubulopapillary neoplasm is a relatively recently described member of the pancreatic intraductal neoplasm family. The more common member of this family, intraductal papillary mucinous neoplasm, often carries genetic alterations typical of pancreatic infiltrating ductal adenocarcinoma (KRAS, TP53, and CDKN2A) but additionally has mutations in GNAS and RNF43 genes. However, the genetic characteristics of intraductal tubulopapillary neoplasm have not been well characterized. Twenty-two intraductal tubulopapillary neoplasms were analyzed by either targeted next-generation sequencing, which enabled the identification of sequence mutations, copy number alterations, and selected structural rearrangements involving all targeted (≥300) genes, or whole-exome sequencing. Three of these intraductal tubulopapillary neoplasms were also subjected to whole-genome sequencing. All intraductal tubulopapillary neoplasms revealed the characteristic histologic (cellular intraductal nodules of back-to-back tubular glands lined by predominantly cuboidal cells with atypical nuclei and no obvious intracellular mucin) and immunohistochemical (immunolabeled with MUC1 and MUC6 but were negative for MUC2 and MUC5AC) features. By genomic analyses, there was loss of CDKN2A in 5/20 (25%) of these cases. However, the majority of the previously reported intraductal papillary mucinous neoplasm-related alterations were absent. Moreover, in contrast to most ductal neoplasms of the pancreas, MAP-kinase pathway was not involved. In fact, 2/22 (9%) of intraductal tubulopapillary neoplasms did not reveal any mutations in the tested genes. However, certain chromatin remodeling genes (MLL1, MLL2, MLL3, BAP1, PBRM1, EED, and ATRX) were found to be mutated in 7/22 (32%) of intraductal tubulopapillary neoplasms and 27% harbored phosphatidylinositol 3-kinase (PI3K) pathway (PIK3CA, PIK3CB, INPP4A, and PTEN) mutations. In addition, 4/18 (18%) of intraductal tubulopapillary neoplasms had FGFR2 fusions (FGFR2-CEP55, FGFR2-SASS6, DISP1-FGFR2, FGFR2-TXLNA, and FGFR2-VCL) and 1/18 (5.5%) had STRN-ALK fusion. Intraductal tubulopapillary neoplasm is a distinct clinicopathologic entity in the pancreas. Although its intraductal nature and some clinicopathologic features resemble those of intraductal papillary mucinous neoplasm, our results suggest that intraductal tubulopapillary neoplasm has distinguishing genetic characteristics. Some of these mutated genes are potentially targetable. Future functional studies will be needed to determine the consequences of these gene alterations.

Mucinous cystadenocarcinoma of the breast: the challenge of diagnosing a rare entity.

Mucinous cystadenocarcinoma is an extremely rare variant of primary breast tumor which is histologically similar to mucinous cystadenocarcinoma of the ovary and pancreas. Herein we report a case of a 63 years old woman diagnosed with diverse histological types of non-synchronous rare primary breast tumors, a medullary carcinoma of the right breast and a mucinous cystadenocarcinoma of the left breast. Macroscopically the neoplasm appeared multilocular filled with mucoid material. Under light microscopy the cystic areas were lined by columnar cells with abundant intracellular and extracellular mucin. Solid areas were composed of tall columnar cells with intracellular mucin. Moderate to marked atypia was noticed and tumor cells stained positive for cytokeratin 7 and negative for cytokeratin 20. Moreover tumor cells displayed a basal like immunophenotype expressed as followed: ER negative, PR negative, HER-2 negative, cytokeratin (CK5/6) positive and EGFR positive.

Rebamipide upregulates mucin secretion of intestinal goblet cells via Akt phosphorylation.

Mucin is produced and secreted by epithelial goblet cells and is a key component of the innate immune system, acting as a barrier in the intestinal tract. However, no studies have been conducted investigating the increase in mucin secretion to enhance the intestinal barrier function. The present study investigated whether rebamipide (Reb) acts as a secretagogue of intestinal mucin and the underlying mechanisms involved, thereby focusing on the effect on goblet cells. The LS174T cell line was used as goblet cell‑like cells. Using Reb‑treated LS174T cells, the level of mucin content was assessed by periodic acid‑Schiff (PAS) staining, and mucin 2, oligomeric mucus/gel‑forming (MUC2) mRNA expression was assessed using quantitative polymerase chain reaction (PCR). Furthermore, MUC2 secretion in the supernatant was quantified by the dot blot method. The present study additionally investigated the involvement of the epidermal growth factor receptor/Akt serine/threonine kinase1 (Akt) pathway in mucin secretion by western blotting. The results suggested that Reb strongly enhanced the positivity of PAS staining in LS174T cells, thereby suggesting increased intracellular mucin production. The PCR results indicated that Reb significantly increased MUC2 mRNA in whole cell lysate of LS174T cells. In order to assess the subsequent secretion of mucin by LS174T, MUC2 protein expression in the supernatant was assessed using the dot blot method and it was demonstrated that Reb significantly increased the secretion of MUC2 in a concentration‑dependent manner. The p‑Akt was significantly increased by Reb treatment, and an Akt inhibitor specifically suppressed MUC2 secretion. Overall, Reb increased mucin secretion directly via p‑Akt. Reb‑increased mucin may act as a strong non‑specific barrier against pathogenic stimulants in various intestinal diseases.

Newly Described Entities in Salivary Gland Pathology.

Salivary glands may give rise to a wide spectrum of different tumors. This review concentrates on 4 salivary gland tumors that have been accepted in the recent literature as new neoplastic entities: mammary analog secretory carcinoma, cribriform adenocarcinoma of minor salivary glands (CASG), sclerosing polycystic adenosis/adenoma (SPA), and the mucinous/secretory variant of myoepithelioma. Mammary analog secretory carcinoma is a distinctive low-grade malignant salivary cancer that harbors a characteristic chromosomal translocation, t(12;15) (p13;q25), resulting in an ETV6-NTRK3 fusion. Cribriform adenocarcinoma (CASG) is a distinct tumor entity that differs from polymorphous low-grade adenocarcinoma by location (ie, most often arising on the tongue), by prominent nuclear clearing, differing alterations of the PRKD gene family, and clinical behavior with frequent metastases at the time of presentation of the primary tumor. Early nodal metastatic disease is seen in most cases of CASG; yet, they are still associated with indolent clinical behavior, making it a unique neoplasm among all low-grade salivary gland tumors. SPA is a rare sclerosing tumor of the salivary glands characterized by the combination of cystic ductal structures with variable cell lining including vacuolated, apocrine, mucinous, squamous, and foamy cells, by prominent large acinar cells with coarse eosinophilic cytoplasmic zymogen-like granules, and by closely packed ductal structures, surrounded by a peripheral myoepithelial layer and stromal fibrosis with focal inflammatory infiltrates. SPA frequently harbors intraductal epithelial dysplastic proliferations ranging from mild dysplasia to severe dysplasia/carcinoma in situ. Moreover, SPA has been proven to be a clonal process by HUMARA assay and is associated with considerable risk of recurrence. Therefore, on the basis of all these newly recognized findings, we believe that SPA is likely a neoplasm, and we suggest the name "sclerosing polycystic adenoma." The mucinous variant of myoepithelioma is a myoepithelial tumor with foci of prominent cytoplasmic clearing frequently containing intracellular mucin material and having signet-ring morphology.

Atypical aspirates of the breast: a dilemma in current cytology practice

AimsThe probabilistic approach is widely adopted for breast fine needle aspiration cytology. However, a definite cytological diagnosis is not always possible for C3 (atypia) cases, which poses a management dilemma...

Invasive lobular carcinoma with extracellular mucin production-a novel pattern of lobular carcinomas of the breast. Clinico-pathological description of eight cases.

Invasive lobular carcinoma of the breast is known to produce intracellular mucin and has been recognized in single-case reports to show extracellular mucin production, as well. This latter morphology is not only rare but must also be under- or misdiagnosed. The aim was to better characterize this entity. Cases of lobular cancers demonstrating extracellular mucin formation were identified in a multi-institutional effort and their clinical and morphologic features were assessed. Immunohistochemistry was used to characterize the E-cadherin-membrane complex, neuroendocrine differentiation, and to some extent, mucin formation. All but one of the eight cases occurred in postmenopausal patients. Extracellular mucin production was present in 5 to 50% of the tumour samples and rarely also appeared in nodal and distant metastases. The tumours were completely E-cadherin negative and showed cytoplasmic p120 positivity. The majority (n=6/8) was also completely negative for β-catenin, but two tumours displayed focal β-catenin positivity in the mucinous area. MUC1 and MUC2 expression was observed in all and 7/8 tumours, respectively; neuroendocrine differentiation was present in only one. Invasive lobular carcinoma with extracellular mucin formation is a rare morphologic variant of lobular carcinoma prone to be misdiagnosed and warranting further studies.

Pancreatic intraductal tubulopapillary neoplasm with associated invasive cancer successfully treated by total pancreatectomy: A case report.

A 74-year-old male was admitted to Departments of Surgery, Toyonaka Municipal Hospital (Osaka, Japan) for treatment of a pancreatic tumor. Contrast enhanced computed tomography (CT) revealed a mass with small cystic lesions in the pancreatic head and body. Fluorodeoxyglucose-positron emission tomography/CT revealed an abnormal uptake of fluorodeoxyglucose, corresponding to the mass lesions. Upper gastrointestinal endoscopy revealed rough mucosa near the opening of the accessory pancreatic duct, and the mucosa biopsy exhibited adenocarcinoma with no mucin observed. The preoperative diagnosis was pancreatic intraductal tubulopapillary neoplasm (ITPN) with cancerous lesions, and a total pancreatectomy with splenectomy was performed. The resected tissue specimen revealed a solid tumor occupying the entire pancreas with intraductal growth into the main pancreatic duct. Histological examination revealed high-grade dysplastic cells in a tubulopapillary growth pattern without overt mucin production beyond the pancreatic duct. Immunohistochemical staining analysis of the tumor was positive for cytokeratin (CK)7, CK19 and mucin (MUC)1, and negative for MUC2, MUC5AC, MUC6 and caudal type homeobox 2. The tumor was finally diagnosed as pancreatic ITPN with associated invasive cancer. The patient remains well without evident recurrence nine months post-surgery. ITPN is a rare type of epithelial neoplasm of the pancreas, and is characterized by intraductal tubulo-papillary growth, ductal differentiation, limited intracellular mucin production, and cellular dysplasia. The present case report may contribute to improved understanding of how to effectively treat patients with ITPN.