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Autopsy & Case Reports 2022Papillary cystadenocarcinoma of the salivary gland is a very rare malignant neoplasm accounting for only 2% of all salivary gland lesions. In 1991 it was first included... (Review)
Review
Papillary cystadenocarcinoma of the salivary gland is a very rare malignant neoplasm accounting for only 2% of all salivary gland lesions. In 1991 it was first included as a separate entity in the World Health Organization (WHO) classification of salivary gland tumors and in 2017 WHO Classification, the tumor was clubbed as a sub-variant of adenocarcinoma, not otherwise specified. It most commonly occurs in the major salivary glands. Herein we report a case of salivary papillary cystadenocarcinoma in a 54-year-old female, who presented with rapid enlargement of the right parotid swelling. Based on radiology and fine-needle aspiration cytology, a working diagnosis of the malignant tumor involving the superficial lobe of the right parotid gland was made. In view of the malignant nature of the swelling, superficial parotidectomy was done. The histopathology and immunohistochemistry of the mass confirmed the diagnosis of papillary cystadenocarcinoma of the right parotid. With the revised 2017 WHO classification of salivary gland tumors, it is important to report all rare subtypes in order to understand their biology and behavior.
PubMed: 35252049
DOI: 10.4322/acr.2021.357 -
Journal of Oral Biology and... 2017A 68-year-old Caucasian gentleman presented with a 6-month history of a left sided Level I/II neck swelling involving the floor of mouth. MRI revealed a large cystic...
A 68-year-old Caucasian gentleman presented with a 6-month history of a left sided Level I/II neck swelling involving the floor of mouth. MRI revealed a large cystic lesion and histology confirmed a diagnosis of primary papillary cystadenocarcinoma of the sublingual gland. Papillary cystadenocarcinoma was first described in 1991 by the World Health Organisation [WHO], and is a rare malignant neoplasm characterised by cysts and papillary endo-cystic projections. Papillary cystadenocarcinoma arising from the sublingual glands is extremely rare and has the potential to metastasise to cervical lymph nodes. This patient we report was therefore treated with surgical excision and post-operative radiotherapy.
PubMed: 29124004
DOI: 10.1016/j.jobcr.2017.03.003 -
Genome Medicine May 2020Distinct prevalence of inherited genetic predisposition may partially explain the difference of cancer risks across ancestries. Ancestry-specific analyses of germline...
BACKGROUND
Distinct prevalence of inherited genetic predisposition may partially explain the difference of cancer risks across ancestries. Ancestry-specific analyses of germline genomes are required to inform cancer genetic risk and prognosis of diverse populations.
METHODS
We conducted analyses using germline and somatic sequencing data generated by The Cancer Genome Atlas. Collapsing pathogenic and likely pathogenic variants to cancer predisposition genes (CPG), we analyzed the association between CPGs and cancer types within ancestral groups. We also identified the predisposition-associated two-hit events and gene expression effects in tumors.
RESULTS
Genetic ancestry analysis classified the cohort of 9899 cancer cases into individuals of primarily European (N = 8184, 82.7%), African (N = 966, 9.8%), East Asian (N = 649, 6.6%), South Asian (N = 48, 0.5%), Native/Latin American (N = 41, 0.4%), and admixed (N = 11, 0.1%) ancestries. In the African ancestry, we discovered a potentially novel association of BRCA2 in lung squamous cell carcinoma (OR = 41.4 [95% CI, 6.1-275.6]; FDR = 0.002) previously identified in Europeans, along with a known association of BRCA2 in ovarian serous cystadenocarcinoma (OR = 8.5 [95% CI, 1.5-47.4]; FDR = 0.045). In the East Asian ancestry, we discovered one previously known association of BRIP1 in stomach adenocarcinoma (OR = 12.8 [95% CI, 1.8-90.8]; FDR = 0.038). Rare variant burden analysis further identified 7 suggestive associations in African ancestry individuals previously described in European ancestry, including SDHB in pheochromocytoma and paraganglioma, ATM in prostate adenocarcinoma, VHL in kidney renal clear cell carcinoma, FH in kidney renal papillary cell carcinoma, and PTEN in uterine corpus endometrial carcinoma. Most predisposing variants were found exclusively in one ancestry in the TCGA and gnomAD datasets. Loss of heterozygosity was identified for 7 out of the 15 African ancestry carriers of predisposing variants. Further, tumors from the SDHB or BRCA2 carriers showed simultaneous allelic-specific expression and low gene expression of their respective affected genes, and FH splice-site variant carriers showed mis-splicing of FH.
CONCLUSIONS
While several CPGs are shared across patients, many pathogenic variants are found to be ancestry-specific and trigger somatic effects. Studies using larger cohorts of diverse ancestries are required to pinpoint ancestry-specific genetic predisposition and inform genetic screening strategies.
Topics: Ataxia Telangiectasia Mutated Proteins; BRCA2 Protein; Fanconi Anemia Complementation Group Proteins; Female; Genetic Predisposition to Disease; Germ-Line Mutation; Humans; Male; Neoplasms; RNA Helicases; Risk Factors; Succinate Dehydrogenase; Von Hippel-Lindau Tumor Suppressor Protein
PubMed: 32471518
DOI: 10.1186/s13073-020-00744-3 -
Modern Pathology : An Official Journal... Jan 2016Serous carcinoma (SC) represents ~10% of endometrial carcinomas, but is responsible for almost 40% of cancer deaths. This article reviews the main pathological features,... (Review)
Review
Serous carcinoma (SC) represents ~10% of endometrial carcinomas, but is responsible for almost 40% of cancer deaths. This article reviews the main pathological features, differential diagnosis, and the usefulness of molecular pathology and immunohistochemistry in its diagnosis. Most helpful features for the diagnosis include: irregularly shaped and sized papillae, slit-like spaces, cell stratification and budding, highly atypical cells, architectural and cytological discordance in pseudoglandular tumors, as well as lack of endometrioid features. SC shows typically a predominant papillary growth, which is also found in some subtypes of endometrioid carcinoma of the endometrium (EEC). Distinction is easy when attention is paid to the presence of diffuse marked nuclear pleomorphism, but also to the complex papillary architecture. SC may also show a solid or pseudoglandular patterns, and in these cases differential diagnosis may be difficult with EEC grade 3. Moreover, a high proportion of SC may exhibit clear cells, and, thus, may be confused with clear cell carcinoma. Finally, it is sometimes difficult to distinguish mixed SC-EEC, from SC that combines papillary and pseudoglandular growths. Although there is not a single immunohistochemical marker for distinguishing SC from its mimickers, some antibodies are useful (p53, p16, IMP2, and IMP3), particularly when used in combination. Diagnosis of SC may be even more problematic in small biopsies; a diagnosis of high-grade endometrial carcinoma, SC component can not be excluded, is acceptable as a managerial approach, so it could be taken into account at the time of final surgery.
Topics: Cystadenocarcinoma, Serous; Endometrial Neoplasms; Female; Humans
PubMed: 26715173
DOI: 10.1038/modpathol.2015.141 -
Surgical Oncology Clinics of North... Apr 2016Management of cystic neoplasms of the pancreas is challenging as it relies on radiologic and cyst fluid markers to discriminate between benign and pre-cancerous lesions,... (Review)
Review
Management of cystic neoplasms of the pancreas is challenging as it relies on radiologic and cyst fluid markers to discriminate between benign and pre-cancerous lesions, however their ability to predict malignancy is limited. While asymptomatic serous cystadenomas can be managed conservatively, mucinous cystic neoplasms and intraductal papillary mucinous neoplasms are more difficult to manage. A selective approach, based on the preoperative likelihood of high-grade dysplasia or invasive disease, is the standard of care. Research is focusing on the development of pre-operative markers for identifying high risk lesions, which will spare patients with low-risk or benign lesions the risks of pancreatectomy.
Topics: Cystadenocarcinoma, Mucinous; Cystadenoma, Mucinous; Cystadenoma, Serous; Humans; Pancreatic Cyst; Pancreatic Neoplasms
PubMed: 27013369
DOI: 10.1016/j.soc.2015.11.006 -
Gynecologic Oncology Jul 2023Low-grade serous ovarian carcinoma (LGSOC) is a distinct, rare, ovarian cancer type characterised by younger patient age and intrinsic chemoresistance. Understanding the...
OBJECTIVES
Low-grade serous ovarian carcinoma (LGSOC) is a distinct, rare, ovarian cancer type characterised by younger patient age and intrinsic chemoresistance. Understanding the molecular landscape is crucial for optimising targeted therapy.
METHODS
Genomic data from whole exome sequencing of tumour tissue was analysed in a LGSOC cohort with detailed clinical annotation.
RESULTS
63 cases were analysed and three subgroups identified based on single nucleotide variants: canonical MAPK mutant (cMAPKm: 52%, KRAS/BRAF/NRAS), MAPK-associated gene mutation (MAPK-assoc: 27%) and MAPK wild-type (MAPKwt: 21%). NOTCH pathway disruption occurred across all subgroups. Tumour mutational burden (TMB), mutational signatures and recurrent copy number (CN) changes varied across the cohort with co-occurrence of chromosome 1p loss and 1q gain (CN Chr1pq) a recurrent feature. Low TMB and CN Chr1pq were associated with inferior disease-specific survival (HR 6.43; p < 0.001 and HR 3.29, p = 0.011 respectively). Stepwise genomic classification in relation to outcome resulted in four groups (TMB low; CN Chr1pq; MAPKwt/MAPKassoc; cMAPKm). 5 year disease-specific survival was 46%, 55%, 79% and 100% respectively for these groups. The two most favourable genomic subgroups were enriched for the SBS10b mutational signature, particularly the cMAPKm subgroup.
CONCLUSIONS
LGSOC comprises multiple genomic subgroups with distinct clinical and molecular features. Chr1pq CN arm disruption and TMB represent promising methods to identify individuals with poorer prognosis. Further investigation of the molecular basis for these observations is required. MAPKwt cases represent around a fifth of patients. NOTCH inhibitors represent a candidate therapeutic strategy worthy of exploration across these cases.
Topics: Female; Humans; Exome Sequencing; Ovarian Neoplasms; Cystadenocarcinoma, Serous; Mutation; Biomarkers, Tumor; Cystadenocarcinoma, Papillary; Genomics
PubMed: 37207500
DOI: 10.1016/j.ygyno.2023.04.011 -
Human Pathology Jun 2021With major advancements and frequent use of abdominal imaging techniques, hepatic cysts are increasingly encountered in clinical practice. Although the majority of cysts... (Review)
Review
With major advancements and frequent use of abdominal imaging techniques, hepatic cysts are increasingly encountered in clinical practice. Although the majority of cysts are benign, a small subset represents neoplastic precursors to cholangiocarcinoma. These cystic precursors include intraductal papillary neoplasms of the bile duct (IPNB) and mucinous cystic neoplasms of the liver (MCN-L), and bear striking pathologic resemblance to corresponding cystic neoplastic precursors within the pancreas. This review examines the salient clinical, gross, microscopic and molecular features of IPNBs and MCN-Ls, and, in particular, provides histopathologic comparison to their pancreatic counterparts. Considering these neoplasms may be diagnostically challenging, we also discuss other hepatic lesions within the differential diagnosis, and the potential for molecular methods to improve their preoperative evaluation and the early detection of cholangiocarcinoma.
Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Cystadenocarcinoma, Mucinous; Diagnosis, Differential; Humans; Liver Neoplasms
PubMed: 33383041
DOI: 10.1016/j.humpath.2020.12.010 -
Frontiers in Immunology 2022Adenosine deaminase (ADA) plays an important role in immune response, which includes two isoenzymes: ADA1 and ADA2. This study aims to explore the roles of ADA1 and ADA2...
OBJECTIVE
Adenosine deaminase (ADA) plays an important role in immune response, which includes two isoenzymes: ADA1 and ADA2. This study aims to explore the roles of ADA1 and ADA2 in cancers.
METHODS
Human Protein Atlas (HPA) and Gene Expression Profiling Interactive Analysis (GEPIA2) databases were used to analyze the mRNA expression of ADA1 and ADA2 in human normal cells and tumor tissues. The enzyme assay was used to detect the ADA1 and ADA2 activities in serum from cancer patients. The Kaplan-Meier (KM) plotter was used to analyze the prognostic value of ADA1 and ADA2. TIMER2.0 was used to explore how ADA1 and ADA2 correlate with immune infiltration and immune checkpoints. cBioPortal database was used to investigate the mutations of ADA1 and ADA2. LinkedOmics was used to screen the ADA1 and ADA2 expression-related genes.
RESULTS
ADA1 was significantly increased in several tumor tissues, including cholangiocarcinoma (CHOL), lymphoid neoplasm diffuse large B-cell lymphoma (DLBC), head and neck squamous cell carcinoma (HNSC), kidney renal clear cell carcinoma (KIRC), ovarian serous cystadenocarcinoma (OV), pancreatic adenocarcinoma (PAAD), thymoma (THYM), and uterine carcinosarcoma (UCS). ADA2 expression was significantly increased in esophageal carcinoma (ESCA), glioblastoma multiforme (GBM), acute myeloid leukemia (LAML), OV, PAAD, skin cutaneous melanoma (SKCM), and stomach adenocarcinoma (STAD). There were no significant changes in serum ADA1 activities in most cancers, while serum ADA2 activities were increased in most cancers. For prognosis, high ADA1 expression was associated with the poor survival in several cancers, including esophageal squamous cell carcinoma (ESCC), HNSC, KIRC, kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), and uterine corpus endometrial carcinoma (UCEC). However, high ADA2 expression showed a favorable prognosis in breast invasive carcinoma (BRCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), HNSC, KIRC, KIRP, LUAD, OV, PAAD, sarcoma, and THYM. ADA1 showed a moderate positive correlation with multiple infiltrating immune cells in most cancers. ADA2 was positively correlated with B cells, CD8 T cells, monocytes/macrophages, and dendritic cells (DCs) and was strongly negatively correlated with myeloid-derived suppressor cells. Function analysis showed that ADA1 expression-related genes were mainly enriched in cell division biological progression. However, ADA2-related genes were mainly associated with immune response.
CONCLUSION
As isoenzymes, ADA1 and ADA2 showed opposite prognostic values and different correlative patterns with immune infiltrating. These data demonstrated the distinct roles of ADA1 and ADA2 in cancer. ADA2 might act as a protective factor in cancer.
Topics: Adenocarcinoma; Adenocarcinoma of Lung; Adenosine Deaminase; Carcinoma, Renal Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Head and Neck Neoplasms; Humans; Isoenzymes; Kidney Neoplasms; Lung Neoplasms; Melanoma; Pancreatic Neoplasms; Skin Neoplasms; Squamous Cell Carcinoma of Head and Neck; Melanoma, Cutaneous Malignant
PubMed: 35663977
DOI: 10.3389/fimmu.2022.903461 -
Computational and Structural... 2022The SARS-CoV-2 is constantly mutating, and the new coronavirus such as Omicron has spread to many countries around the world. Anexelekto (AXL) is a transmembrane protein...
The SARS-CoV-2 is constantly mutating, and the new coronavirus such as Omicron has spread to many countries around the world. Anexelekto (AXL) is a transmembrane protein with biological functions such as promoting cell growth, migration, aggregation, metastasis and adhesion, and plays an important role in cancers and coronavirus disease 2019 (COVID-19). Unlike angiotensin-converting enzyme 2 (ACE2), AXL was highly expressed in respiratory system cells. In this study, we verified the AXL expression in cancer and normal tissues and found AXL expression was strongly correlated with cancer prognosis, tumor mutation burden (TMB), the microsatellite instability (MSI) in most tumor types. Immune infiltration analysis also demonstrated that there was an inextricable link between AXL expression and immune scores in cancer patients, especially in BLCA, BRCA and CESC. The NK-cells, plasmacytoid dendritic cells, myeloid dendritic cells, as one of the important components of the tumor microenvironment, were highly expressed AXL. In addition, AXL-related tumor neoantigens were identified and might provide the novel potential targets for tumor vaccines or SARS-Cov-2 vaccines research in cancer patients.
PubMed: 35782741
DOI: 10.1016/j.csbj.2022.06.051 -
Translational Cancer Research Dec 2022Mucinous cystadenocarcinoma (MCA) mainly occurs in the ovary, pancreas, and appendix, whereas the breast is a rare primary site of occurrence. Invasive ductal carcinoma...
BACKGROUND
Mucinous cystadenocarcinoma (MCA) mainly occurs in the ovary, pancreas, and appendix, whereas the breast is a rare primary site of occurrence. Invasive ductal carcinoma (IDC) is the most common breast malignancy. Only 31 cases of the breast MCA have been reported in the English literature, and the coexistence of MCA and IDC in the breast are rare.
CASE DESCRIPTION
Here, we describe a 61-year-old postmenopausal woman with no family history of breast cancer or other breast-related diseases, who presented with a palpable mass in her left breast lasting for 2 months. On ultrasonography examination, the tumor was a cystic-solid lesion with clear boundary. Magnetic resonance imaging (MRI) showed a mass with low signal intensity on T1 weighted imaging and high signal intensity on T2 weighted imaging. Intraoperative frozen sections revealed metastatic tumor cells in one sentinel lymph node (1/4). She then underwent left modified radical mastectomy with axillary dissection. The post-operative pathological examination showed the tumor consisted mostly of MCA (60%), with a small proportion of intermediate-grade IDC. The MCA had a well-demarcated cystic structure with papillary projections and abundant mucoid material. The epithelium lining cystic spaces was tall columnar, with mucin-producing cells that had basally located nuclei. The degree of cytological atypia varied considerably. Axillary lymph nodes were normal (0/15). The MCA was triple-negative for estrogen receptor (ER), progesterone receptor (PR), and HER2, and positive for CK7 but negative for CK20. Through next-generation sequencing, no mutations in the and genes were identified in our case, which was not highlighted in prior cases. After surgery, the patient underwent eight cycles of chemotherapy, and she has been disease-free during the 10-month follow-up. In addition to detailing this instance of mixed MCA and IDC of the breast, we reviewed relevant literature and compare our findings with other patients who had breast MCAs.
CONCLUSIONS
Our results improved the understanding of mixed MCA and IDC, especially MCA, and provided a basis for its diagnosis and differential diagnosis from other metastatic diseases.
PubMed: 36644191
DOI: 10.21037/tcr-22-1596