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Head and Neck Pathology Mar 2022The salivary gland section in the 5th edition of the World Health Organization Classification of Head and Neck Tumours features a description and inclusion of several...
The salivary gland section in the 5th edition of the World Health Organization Classification of Head and Neck Tumours features a description and inclusion of several new entities, including sclerosing polycystic adenoma, keratocystoma, intercalated duct adenoma, and striated duct adenoma among the benign neoplasms; and microsecretory adenocarcinoma and sclerosing microcystic adenocarcinoma as the new malignant entities. The new entry also includes mucinous adenocarcinoma subdivided into papillary, colloid, signet ring, and mixed subtypes with recurrent AKT1 E17K mutations across patterns suggesting that mucin-producing salivary adenocarcinomas represent a histologically diverse single entity that may be related to salivary intraductal papillary mucinous neoplasm (IPMN). Importantly, the number of entities in the salivary chapter has been reduced by omitting tumors or lesions if they do not occur exclusively or predominantly in salivary glands, including hemangioma, lipoma, nodular fasciitis and hematolymphoid tumors. They are now discussed in detail elsewhere in the book. Cribriform adenocarcinoma of salivary gland origin (CASG) now represents a distinctive subtype of polymorphous adenocarcinoma (PAC). PAC is defined as a clinically, histologically and molecularly heterogeneous disease group. Whether CASG is a different diagnostic category or a variant of PAC is still controversial. Poorly differentiated carcinomas and oncocytic carcinomas are discussed in the category "Salivary carcinoma not otherwise specified (NOS) and emerging entities". New defining genomic alterations have been characterized in many salivary gland tumors. In particular, they include gene fusions, which have shown to be tightly tumor-type specific, and thus valuable for use in diagnostically challenging cases. The recurrent molecular alterations were included in the definition of mucoepidermoid carcinoma, adenoid cystic carcinoma, secretory carcinoma, polymorphous adenocarcinoma, hyalinizing clear cell carcinoma, mucinous adenocarcinoma, and microsecretory adenocarcinoma.
Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adenoma; Biomarkers, Tumor; Humans; Salivary Gland Neoplasms; Salivary Glands; World Health Organization
PubMed: 35312980
DOI: 10.1007/s12105-022-01420-1 -
Breast (Edinburgh, Scotland) Feb 2020Mucinous carcinoma (MC) is a rare breast cancer characterized by the presence of large extracellular mucin amount. Two main subtypes can be distinguished: pure (PMC) and... (Review)
Review
Mucinous carcinoma (MC) is a rare breast cancer characterized by the presence of large extracellular mucin amount. Two main subtypes can be distinguished: pure (PMC) and mixed (MMC). We conducted a retrospective MC analysis in our prospective maintained database, calculating disease-free survival (DFS) and 5-year overall survival (OS). We found a global 92.1% OS (higher in MMC group and statistically significative) and a DFS of 95.3% (higher in MMC group but not statistically significative).
Topics: Adenocarcinoma, Mucinous; Adult; Aged; Aged, 80 and over; Breast Neoplasms; Combined Modality Therapy; Databases, Factual; Female; Follow-Up Studies; Humans; Italy; Middle Aged; Prognosis; Retrospective Studies; Survival Analysis; Tertiary Care Centers
PubMed: 31783314
DOI: 10.1016/j.breast.2019.11.002 -
International Journal of Biological... 2021Pancreatic adenosquamous carcinoma (PASC) - a rare pathological pancreatic cancer (PC) type - has a poor prognosis due to high malignancy. To examine the heterogeneity...
Pancreatic adenosquamous carcinoma (PASC) - a rare pathological pancreatic cancer (PC) type - has a poor prognosis due to high malignancy. To examine the heterogeneity of PASC, we performed single-cell RNA sequencing (scRNA-seq) profiling with sample tissues from a healthy donor pancreas, an intraductal papillary mucinous neoplasm, and a patient with PASC. Of 9,887 individual cells, ten cell subpopulations were identified, including myeloid, immune, ductal, fibroblast, acinar, stellate, endothelial, and cancer cells. Cancer cells were divided into five clusters. Notably, cluster 1 exhibited stem-like phenotypes expressing UBE2C, ASPM, and TOP2A. We found that S100A2 is a potential biomarker for cancer cells. LGALS1, NPM1, RACK1, and PERP were upregulated from ductal to cancer cells. Furthermore, the copy number variations in ductal and cancer cells were greater than in the reference cells. The expression of EREG, FCGR2A, CCL4L2, and CTSC increased in myeloid cells from the normal pancreas to PASC. The gene sets expressed by cancer-associated fibroblasts were enriched in the immunosuppressive pathways. We demonstrate that EGFR-associated ligand-receptor pairs are activated in ductal-stromal cell communications. Hence, this study revealed the heterogeneous variations of ductal and stromal cells, defined cancer-associated signaling pathways, and deciphered intercellular interactions following PASC progression.
Topics: Adenocarcinoma, Mucinous; Biomarkers, Tumor; Carcinoma, Adenosquamous; Chemotactic Factors; DNA Copy Number Variations; ErbB Receptors; Genetic Heterogeneity; Humans; Neoplasm Proteins; Pancreatic Neoplasms; S100 Proteins; Sequence Analysis, RNA; Single-Cell Analysis; Transcriptome
PubMed: 34326696
DOI: 10.7150/ijbs.58886 -
Cancer Research May 2023The endoderm-lineage transcription factor FOXA2 has been shown to inhibit lung tumorigenesis in in vitro and xenograft studies using lung cancer cell lines. However,...
UNLABELLED
The endoderm-lineage transcription factor FOXA2 has been shown to inhibit lung tumorigenesis in in vitro and xenograft studies using lung cancer cell lines. However, FOXA2 expression in primary lung tumors does not correlate with an improved patient survival rate, and the functional role of FOXA2 in primary lung tumors remains elusive. To understand the role of FOXA2 in primary lung tumors in vivo, here, we conditionally induced the expression of FOXA2 along with either of the two major lung cancer oncogenes, EGFRL858R or KRASG12D, in the lung epithelium of transgenic mice. Notably, FOXA2 suppressed autochthonous lung tumor development driven by EGFRL858R, whereas FOXA2 promoted tumor growth driven by KRASG12D. Importantly, FOXA2 expression along with KRASG12D produced invasive mucinous adenocarcinoma (IMA) of the lung, a fatal mucus-producing lung cancer comprising approximately 5% of human lung cancer cases. In the mouse model in vivo and human lung cancer cells in vitro, FOXA2 activated a gene regulatory network involved in the key mucous transcription factor SPDEF and upregulated MUC5AC, whose expression is critical for inducing IMA. Coexpression of FOXA2 with mutant KRAS synergistically induced MUC5AC expression compared with that induced by FOXA2 alone. ChIP-seq combined with CRISPR interference indicated that FOXA2 bound directly to the enhancer region of MUC5AC and induced the H3K27ac enhancer mark. Furthermore, FOXA2 was found to be highly expressed in primary tumors of human IMA. Collectively, this study reveals that FOXA2 is not only a biomarker but also a driver for IMA in the presence of a KRAS mutation.
SIGNIFICANCE
FOXA2 expression combined with mutant KRAS drives invasive mucinous adenocarcinoma of the lung by synergistically promoting a mucous transcriptional program, suggesting strategies for targeting this lung cancer type that lacks effective therapies.
Topics: Animals; Humans; Mice; Adenocarcinoma, Mucinous; Hepatocyte Nuclear Factor 3-beta; Lung; Lung Neoplasms; Mice, Transgenic; Mutation; Proto-Oncogene Proteins p21(ras); Transcription Factors
PubMed: 37067057
DOI: 10.1158/0008-5472.CAN-22-2805 -
Journal of Clinical Oncology : Official... Mar 2023Appendiceal adenocarcinomas (ACs) are rare, histologically diverse malignancies treated as colorectal cancers despite having distinct biology and clinical behavior. To...
PURPOSE
Appendiceal adenocarcinomas (ACs) are rare, histologically diverse malignancies treated as colorectal cancers despite having distinct biology and clinical behavior. To guide clinical decision making, we defined molecular subtypes of AC associated with patient survival, metastatic burden, and chemotherapy response.
PATIENTS AND METHODS
A comprehensive molecular analysis was performed in patients with AC to define molecular subtypes. Associations between molecular subtype and overall survival, intraoperative peritoneal cancer index, and first-line chemotherapy response were assessed adjusting for histopathologic and clinical variables using multivariable Cox proportional hazards, linear regression, and logistic regression models.
RESULTS
We defined distinct molecular lineages of mucinous appendiceal adenocarcinoma (MAAP) from co-occurring mutations in , , and . Of 164 MAAP tumors, 24 were RAS-mutant (mut) predominant (-mut/-wild-type [wt]/-wt) with significantly decreased mutations and chromosomal alterations compared with tumors with mutations (GNAS-mut predominant) or mutations (TP53-mut predominant). No patient with RAS-mut predominant subtype metastatic MAAP died of cancer, and overall survival in this subgroup was significantly improved compared with patients with GNAS-mut ( = .05) and TP53-mut ( = .004) predominant subtypes. TP53-mut predominant subtypes were highly aneuploid; increased tumor aneuploidy was independently ( = .001) associated with poor prognosis. The findings retained significance in patients with any metastatic AC. RAS-mut predominant metastases exhibited reduced peritoneal tumor bulk ( = .04) and stromal invasion ( < .001) compared with GNAS-mut or TP53-mut predominant tumors, respectively. Patients with RAS-mut predominant MAAP responded more to first-line chemotherapy (50%) compared with patients with GNAS-mut predominant tumors (6%, = .03).
CONCLUSION
AC molecular patterns identify distinct molecular subtypes: a clinically indolent RAS-mut/GNAS-wt/TP53-wt subtype; a chemotherapy-resistant GNAS-mut predominant subtype; and an aggressive, highly aneuploid TP53-mut predominant subtype. Each subtype exhibits conserved clinical behavior irrespective of histopathology.
Topics: Humans; Adenocarcinoma; Appendiceal Neoplasms; Adenocarcinoma, Mucinous; Mutation; Peritoneal Neoplasms
PubMed: 36493333
DOI: 10.1200/JCO.22.01392 -
Communications Biology Jan 2023Colorectal cancer is a highly heterogeneous disease. Most colorectal cancers are classical adenocarcinoma, and mucinous adenocarcinoma is a unique histological subtype...
Colorectal cancer is a highly heterogeneous disease. Most colorectal cancers are classical adenocarcinoma, and mucinous adenocarcinoma is a unique histological subtype that is known to respond poorly to chemoradiotherapy. The difference in prognosis between mucinous adenocarcinoma and classical adenocarcinoma is controversial. Here, to gain insight into the differences between classical adenocarcinoma and mucinous adenocarcinoma, we analyse 7 surgical tumour samples from 4 classical adenocarcinoma and 3 mucinous adenocarcinoma patients by single-cell RNA sequencing. Our results indicate that mucinous adenocarcinoma cancer cells have goblet cell-like properties, and express high levels of goblet cell markers (REG4, SPINK4, FCGBP and MUC2) compared to classical adenocarcinoma cancer cells. TFF3 is essential for the transcriptional regulation of these molecules, and may cooperate with RPS4X to eventually lead to the mucinous adenocarcinoma mucus phenotype. The observed molecular characteristics may be critical in the specific biological behavior of mucinous adenocarcinoma.
Topics: Humans; Mucins; Adenocarcinoma; Adenocarcinoma, Mucinous; Prognosis; Phenotype; Serine Peptidase Inhibitors, Kazal Type
PubMed: 36690709
DOI: 10.1038/s42003-023-04441-w -
Abdominal Radiology (New York) Nov 2019Rectal adenocarcinoma with mucinous components is an uncommon type of rectal cancer with two distinct histologic subtypes: mucinous adenocarcinoma and signet-ring cell... (Review)
Review
Rectal adenocarcinoma with mucinous components is an uncommon type of rectal cancer with two distinct histologic subtypes: mucinous adenocarcinoma and signet-ring cell carcinoma. Mucin can also be identified as pattern of response after neoadjuvant treatment. On imaging modalities, mucin typically demonstrates high signal intensity on T2-weighted images, low attenuation on computed tomography, and may be negative on 18-fluorodeoxyglucose positron emission tomography. After neoadjuvant CRT, cellular and acellular mucin share similar imaging features, and differentiating them is currently the main challenge faced by radiologists. Radiologists should be aware of pros, cons, and limitations of each imaging modality in the primary staging and restaging to avoid misinterpretation of the radiological findings.
Topics: Adenocarcinoma, Mucinous; Chemoradiotherapy; Humans; Neoadjuvant Therapy; Neoplasm Staging; Rectal Neoplasms
PubMed: 30993392
DOI: 10.1007/s00261-019-02019-x -
Cancer Research Oct 2023Appendiceal adenocarcinomas (AA) are a rare and heterogeneous mix of tumors for which few preclinical models exist. The rarity of AA has made performing prospective...
UNLABELLED
Appendiceal adenocarcinomas (AA) are a rare and heterogeneous mix of tumors for which few preclinical models exist. The rarity of AA has made performing prospective clinical trials difficult, which has partly contributed to AA remaining an orphan disease with no chemotherapeutic agents approved by the FDA for its treatment. AA has a unique biology in which it frequently forms diffuse peritoneal metastases but almost never spreads via a hematogenous route and rarely spreads to lymphatics. Given the localization of AA to the peritoneal space, intraperitoneal delivery of chemotherapy could be an effective treatment strategy. Here, we tested the efficacy of paclitaxel given by intraperitoneal administration using three orthotopic patient-derived xenograft (PDX) models of AA established in immunodeficient NSG mice. Weekly intraperitoneal paclitaxel treatment dramatically reduced AA tumor growth in all three PDX models. Comparing the safety and efficacy of intravenous with intraperitoneal administration, intraperitoneal delivery of paclitaxel was more effective, with reduced systemic side effects in mice. Given the established safety record of intraperitoneal paclitaxel in gastric and ovarian cancers, and lack of effective chemotherapeutics for AA, these data showing the activity of intraperitoneal paclitaxel in orthotopic PDX models of mucinous AA support the evaluation of intraperitoneal paclitaxel in a prospective clinical trial.
SIGNIFICANCE
The activity and safety of intraperitoneal paclitaxel in orthotopic PDX models of mucinous appendiceal adenocarcinoma supports the evaluation of intraperitoneal paclitaxel in a prospective clinical trial of this rare tumor type.
Topics: Female; Humans; Animals; Mice; Paclitaxel; Prospective Studies; Adenocarcinoma, Mucinous; Adenocarcinoma; Ovarian Neoplasms
PubMed: 37433032
DOI: 10.1158/0008-5472.CAN-23-0013 -
Archives of Pathology & Laboratory... Jan 2023Mucinous lesions of the breast encompass many entities ranging from benign to malignant and nonneoplastic to neoplastic. Lesions discussed under this category are... (Review)
Review
CONTEXT.—
Mucinous lesions of the breast encompass many entities ranging from benign to malignant and nonneoplastic to neoplastic. Lesions discussed under this category are mucocele-like lesion, mucinous carcinoma, mucinous micropapillary carcinoma, solid papillary carcinoma, mucinous cystadenocarcinoma, mucoepidermoid carcinoma, invasive lobular carcinoma with extracellular mucin, mucinous ductal carcinoma in situ, and metastasis.
OBJECTIVE.—
To review clinical, pathologic, and molecular features of mucinous lesions of the breast, their differential diagnoses, and challenging features on core needle biopsies.
DATA SOURCES.—
The existing scientific and clinical literature as of December 2021.
CONCLUSIONS.—
The category of mucinous lesions of the breast is vast and the differential diagnosis can be challenging, especially on core needle biopsies. In all cases, clinical, radiologic, and pathologic correlation is necessary to reach a comprehensive diagnosis. Given that the prognosis and management of each entity is different, being aware of these entities and their nuances is critical for a pathologist to guide accurate management.
Topics: Female; Humans; Adenocarcinoma, Mucinous; Biopsy, Large-Core Needle; Breast; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating
PubMed: 36577093
DOI: 10.5858/arpa.2022-0054-RA -
Journal of Personalized Medicine Nov 2020There is a need to personalize the treatment for rectal cancer patients. The aim of this study was to analyze therapy response and prognosis after preoperative...
There is a need to personalize the treatment for rectal cancer patients. The aim of this study was to analyze therapy response and prognosis after preoperative radiotherapy in rectal cancer patients with mucinous adenocarcinoma compared to those with non-mucinous adenocarcinoma. The study included retrospectively collected data from 433 patients, diagnosed with rectal cancer in the South East health care region in Sweden between 2004 and 2012. Patients with non-mucinous adenocarcinoma that received short-course radiotherapy before surgery had better overall survival, cancer specific survival, and disease-free survival, as well as distant- and local-recurrence-free survival ( = 0.003, = 0.001, = 0.002, = 0.002, and = 0.033, respectively) compared to the patients that received long-course radiotherapy with concomitant capecitabine. The results were still significant after adjusting for sex, age, stage, differentiation, and chemotherapy in the neoadjuvant and/or adjuvant setting, except for local-recurrence-free survival that was trending towards significance ( = 0.070). In patients with mucinous adenocarcinoma, no difference in survival was seen when comparing patients that had short-course radiotherapy and patients that had long-course radiotherapy. However, none of 18 patients with mucinous adenocarcinoma treated with long-course radiotherapy had local tumor progression, compared to 7% of 67 patients with non-mucinous adenocarcinoma. The results indicate that mucinous adenocarcinoma and non-mucinous adenocarcinoma may respond differently to radiotherapy.
PubMed: 33202796
DOI: 10.3390/jpm10040226