Acinic Cell Carcinoma Research Articles

Abstract P4-05-07: Whole-exome and RNA-sequencing analyses of acinic cell carcinomas of the breast

Abstract Introduction: Acinic cell carcinoma of the breast (ACC) is an exceedingly rare histologic form of triple-negative breast cancer (TNBC) with a generally good clinical behavior. Despite its unique histology, targeted sequencing analysis of ACC has failed to identify recurrent genetic alterations other than those found in common forms of TNBC. Here, we subjected three breast ACCs to whole-exome and RNA-sequencing, seeking to define whether they would be underpinned by a pathognomonic genetic alteration that would distinguish them from common forms of TNBC. Materials and methods: Three breast ACCs were subjected to whole-exome sequencing (WES) and RNA-sequencing. Somatic mutations, copy number alterations, mutational signatures and fusion genes were determined using a validated bioinformatics pipeline. We also estimated DNA-based measures of genomic instability including mutational signatures (using SigMA), large-scale state transition (LST) and telomeric allelic imbalance (NtAI). Results: No oncogenic in-frame fusion transcript was identified in the breast ACCs analyzed. ACCs displayed a median of 173 (range, 92-230) non-synonymous somatic mutations as defined by WES. We detected clonal TP53 hotspot mutations associated with loss of heterozygosity (LOH) of the wild-type allele in two ACCs (ACC1 and ACC18). In contrast, the TP53 wild-type ACC (ACC12) harbored a pathogenic MLH1 germline mutation (p.Glu227_Ser295del) and a clonal hotspot mutation in CTNNB1 (p.Lys335Ile). No cancer gene other than TP53 was found to be mutated in >1 case. Copy number analysis revealed that ACC18 harbored a BRCA1 homozygous deletion and focal amplification of 20p12.3 encompassing PCNA. Moreover, the TP53-mutant cases, ACC1 and ACC18, displayed complex copy number profiles, with multiple gains and losses and focal high-level amplifications. Consistent with the BRCA1 homozygous deletion, ACC18 displayed genomic features of homologous recombination DNA repair deficiency (HRD), such as a dominant mutational signature 3, a high LST score (24), a high NtAI score (23) and a high number of ‘small deletions’ >5bps. In contrast, and consistent with its DNA mismatch repair (MMR) deficiency, ACC12 had a simple genome without detectable copy number alterations, displayed a dominant mutational signature 6 associated with defective MMR, microsatellite instability (MSI) as determined by MSIsensor and loss of MLH1 expression by immunohistochemical analysis. Conclusions: Our findings lend further support to the notion that ACCs of the breast are genetically heterogeneous and display genomic features overlapping with those of common forms of TNBCs. Although no pathognomonic genetic alterations were detected in these cases, our data suggest that at least some ACCs of the breast may arise in the setting of HRD or MSI through distinct molecular mechanisms. Our data also suggest the possibility that both BRCA1 and TP53 loss of function may not be sufficient for a TNBC to display high-grade features and that inactivation of these two genes may not necessarily result in the development of high-grade TNBC. Citation Format: Francisco Beca, Simon SK Lee, Fresia Pareja, Arnaud Da Cruz Paula, Pier Selenica, Lorenzo Ferrando, Hannah Y Wen, Hong Zhang, Elena Guerini-Rocco, Emad A Rakha, Britta Weigelt, Jorge S Reis-Filho. Whole-exome and RNA-sequencing analyses of acinic cell carcinomas of the breast [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-05-07.

Long-term outcomes and significance of preoperative lymphocyte-to-monocyte ratio as a prognostic indicator in patients with invasive pancreatic neoplasms after repeat pancreatectomy

BackgroundInvasive pancreatic neoplasms have a high propensity for recurrence even after curative resection. Recently, patients who underwent pancreatectomy have an opportunity of undergoing secondary pancreatic resection, so-called “repeat pancreatectomy” to achieve curative operation and prolong their survival. We evaluated the long-term clinical outcomes and identified the prognostic factors, including systemic inflammation markers and the lymphocyte-to-monocyte ratio (LMR) of patients who underwent repeat pancreatectomy for invasive pancreatic tumors.MethodsTwenty-eight consecutive patients with invasive pancreatic neoplasms (22 pancreatic ductal adenocarcinomas, 2 pancreatic acinar cell carcinomas, and 4 invasive intra-papillary mucinous carcinomas) with isolated local recurrence only in the remnant pancreas were analyzed retrospectively. To identify factors for the selection of optimal patients who should undergo repeat pancreatectomy, perioperative clinical parameters were analyzed by Cox proportional regression models.ResultsOf 28 patients, 12 patients experienced recurrence within 3 years after repeat pancreatectomy. Kaplan–Meier analysis showed that the median cancer-specific overall survival time of patients with invasive pancreatic neoplasms was 61 months, showing favorable outcomes. High preoperative LMR (LMR ≥ 3.3) (p = 0.022), no portal vein resection (p = 0.021), no arterial resection (p = 0.037), and pathological lymph node negative (p = 0.0057) were identified as favorable prognostic parameters on univariate analysis, and LMR ≥ 3.3 (p = 0.0005), and pathological lymph node negative (p = 0.018) on multivariate analysis.ConclusionsPreoperative LMR is potentially a good indicator for selecting suitable patients to undergo repeat pancreatectomy in patients with isolated local recurrence of invasive pancreatic neoplasms.

Low-grade variants of triple-negative breast carcinoma (TNBC): a review

Low-grade triple negative breast carcinoma (TNBC) differ from conventional type TNBC in clinical, histologic, immunophenotypic, and molecular features. Salient features of low-grade variants of TNBC including adenoid cystic carcinoma (AdCC), secretory carcinoma, low-grade adenosquamous carcinoma (LGASC) and acinic cell carcinoma (ACC), will be discussed, including those useful in distinguishing these unique entities from more commonly encountered differential diagnoses.

Insulinoma-associated protein 1 (INSM1) is a robust marker for identifying and grading pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumor (PNET) is a diagnostic challenge with limited samples in not only identification but grading. Prior studies have shown insulinoma-associated protein 1 (INSM1) to be a robust marker in identifying PNETs from other solid pancreatic tumors on resection specimens. In this study, we investigated the utility of INSM1 not only for identifying PNETs but also for grading in cell blocks (CBs) and surgical resections (SRs). A search for PNET cases between 2000 and 2019 identified 55 samples (26 CBs and 29 SRs) that were further separated into high (2 CBs, 3 SRs), intermediate (4 CBs, 7 SRs), and low (20 CBs, 19 SRs) grades based on their final pathology report and Ki-67 level. Immunohistochemical (IHC) staining for INSM1 (C-8, Santa Cruz Biotechnology [1:100]) was performed and quantified using an H score of 0 to 300. Non-PNET solid pancreatic tumors were compared and included acinar cell carcinoma, solid pseudopapillary neoplasm, and ductal adenocarcinoma. All 55 cases of PNET demonstrated nuclear INSM1 staining. The average H scores for INSM1 staining of PNET were 254 and 252 in CB and SR, respectively. The H scores decreased with increasing tumor grade, with low-grade (G1), intermediate-grade (G2), and high-grade (G3) tumors showing average INSM1 H scores of 229 and 253, 266 and 253, and 30 and 33 in both CB and SR, respectively. IHC with INSM1 plays a role in identifying and potentially grading PNETs.

An Accuracy Comparison of SOX10 with DOG1 Immunohistochemistry in Diagnosing Acinic Cell Carcinoma of Salivary Gland in Paraffin Tissue Samples

BackgroundMorphological diversity is a challenge in establishing diagnosis of malignant tumor originated from salivary gland, especially Aciniccell carcinoma (ACC). Immunohistochemical (IHC) staining using DOG1 is often used to help diagnosis of ACC. Lately, IHC SOX10has been reported to have almost the same accuracy to DOG1 staining. This evidence-based case report aims to determine theaccuracy of SOX10 to DOG1 immunohistocheinstry staining in establishing a diagnosis of ACC.MethodsLiterature searches were carried out on the Pubmed, Clinical key, Proquest, ScienceDirect, Scopus, SpringerLink and Wileydatabases. Two journals were relevant to the clinical scenario, then a critical review is carried out using the Diagnostic StudyAppraisal Worksheet from the Center for Evidence-based Medicine, University of Oxford, 2010.ResultsThe accuracy of SOX10 in diagnosing ACC was slightly better than DOG1, with sensitivity reaching 100% and specificity reaching87.76%. The sensitivity of SOX10 and DOG1 is the same, but SOX10 is more specific, and positive predictive value is also betterthan DOG1.ConclusionThe accuracy of SOX10 is better than DOG1 in diagnosing ACC of salivary gland. However, the intensity of SOX10 staining tends tobe rather low compared to DOG1. Therefore, further research is still needed to recommend SOX10 staining in daily practice.

Recurrent High Grade Acinic Cell Carcinoma of Minor Salivary Gland-A Case Report

Acinic cell carcinoma (AciCC) is one of the rare malignant tumors of minor salivary gland. Our case is of 52 year old female who presented up with a secondary recurrence of Acinic cell carcinoma in her right cheek, the tumour is characterized by acinar cells with abundant basophilic granular cytoplasm. Surgical resection has been the choice of clinicians and role of radiotherapy is debatable. High grade transformation as seen in this case, merits further studies to know its etiopathogenesis. Long term follow up is required in these patients owing to its late recurrence being now reported in the literature.

Clinicopathologic Features and Survival Trends for Acinic Cell Carcinoma of the Major Salivary Glands: A Surveillance, Epidemiology, and End Results Population Analysis.

BackgroundWe analyzed a population-based national registry to identify the most influential patient pretreatment and treatment factors affecting overall survival (OS) and cause-specific survival (CSS) in patients diagnosed with acinic cell carcinoma (ACC) of the major salivary glands.MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) database of the US National Cancer Institute (NCI) related to survival, a total of 1,254 patients with diagnosed ACC of the major salivary glands from 1975 to 2016 met inclusion criteria. Factors significant for OS and CSS were determined using univariate and multivariate analysis with the Cox proportional hazards model.ResultsUnivariate OS analysis demonstrated that surgery favorably influenced longer survival compared to no surgery (hazard ratio (HR) 2.35, P < 0.05). Patient age was found to be highly predictive of superior OS (divided into 10-year age bands, P < 0.0001, younger age better). In multivariate OS analysis, there were statistically significant worse outcomes for men (HR 1.54, P < 0.05), grades III/IV (HR 2.5, P < 0.05), and distant disease (HR 3.55, P < 0.05) or regional disease (HR 1.22, P < 0.05). Patients diagnosed during years 1996 - 2016 had better OS when compared to earlier decades 1975 - 1995 (HR 1.38, P < 0.05). In univariate analysis, the mean CSS for grades I, II, and III/IV were 429 months (95% confidence interval (CI), ± 38.39), 426 months (95% CI, ± 25.73) and 198 months (95% CI, ± 66.38). Multivariate analysis of CSS further demonstrated that there were statistically significant worse outcomes for men (HR 1.68, P < 0.05), grade III/IV (HR 3.2, P < 0.05), tumor size greater than 40 mm (P < 0.001), and distant disease (HR 4.48, P < 0.05) or regional disease (HR 1.84, P < 0.05).ConclusionsTo our knowledge, this is the largest population-based study of OS and CSS of major salivary gland ACC. We found that the patient pretreatment and treatment factors including younger age at diagnosis, female sex, early stage, lower grade, surgical excision, and recent year of diagnosis are associated with improved survival in patients diagnosed with ACC of the major salivary glands. We hope that this information will aid in construction of further research projects that better refine optimal treatment protocol of individualized patient care.

Characteristics of patients with pancreatic acinar cell carcinoma in comparison with pancreatic ductal adenocarcinoma

Characteristics of patients with pancreatic acinar cell carcinoma in comparison with pancreatic ductal adenocarcinoma

Mammary analogue secretory carcinoma: An Indian experience of a novel entity.

To explore clinical, histopathological and immunohistochemistry (IHC) features of mammary analogue secretory carcinoma (MASC) with systematic literature review. Hospital based cross-sectional study. The data of all cases of MASC diagnosed over a period of 1 year i.e., from July 2017 to July 2018 were retrieved. The haematoxylin and eosin (H and E) sections, and IHC sections were studied. A strict histological and recently updated criteria were applied and patients with a confirmed diagnosis of MASC were included in the study. A systematic literature review was conducted by searching the PubMed and National Centre for Biotechnology Information database. Microsoft Excel 2010. The present case series is 27th in the English literature and 1stcase series describing its histopathology in the Indian literature. The mean age of presentation is 43 years. Female preponderance was found i.e., M:F ratio of 0.5. Histopathology and if necessary, followed by IHC is required for the confirmation of diagnosis of MASC. We should be aware about this recently described entity which is usually mistaken for other low grade salivary gland carcinomas like Acinic cell carcinoma (AciCC) and Mucoepidermoid carcinoma (MEC). The knowledge about its typical morphology, high degree of suspicion and IHC confirmation with both S-100 and Mammaglobin help in precise diagnosis.

A case of acinic cell carcinoma arising in the buccal mucosa: A review of the literature on acinic cell carcinoma of the minor salivary gland in Japan

A case of acinic cell carcinoma arising in the buccal mucosa: A review of the literature on acinic cell carcinoma of the minor salivary gland in Japan

Histo- and clinico-pathological analysis of a large series of triple-negative breast cancer in a single center in China: Evidences on necessity of histological subtyping and grading.

ObjectiveTo investigate histo-pathological distribution and clinico-pathological significance in a large Chinese triple-negative breast cancer (TNBC) patients serials based on the latest understanding of its clinico-pathological diversity, and to provide more information to clinicians to improve precision of individualized treatment of TNBC.MethodsA retrospective analysis was performed on patients with TNBC at Breast Disease Center, Peking University First Hospital between January 2010 and December 2019. Histo- and clinico-pathological characteristics were analyzed by Chi-square test and Student’s t-test, and prognoses were calculated using Kaplan-Meier method and a Cox proportionate hazards model. Bonferroni correction was used to correct for multiple comparison. ResultsConventional type of TNBC (cTNBC) were identified in 73.7% of 582 TNBC, while special type of TNBC (sTNBC) were 26.3%, including 71 apocrine carcinoma, 20 medullary carcinoma, 31 metaplastic carcinoma, 18 invasive lobular carcinoma, 7 invasive micropapillary carcinoma, 5 adenoid cystic carcinoma and 1 acinic cell carcinoma. Compared to sTNBC, cTNBC was associated with high histologic grade (P<0.001) and lower androgen receptor (AR) expression (P<0.001). TNM stage of low-grade cTNBC was significantly lower than that of high-grade cTNBC (P=0.002). Although no significant difference, there was a trend that the rate of 5-year disease-free survival (DFS) and 5-year overall survival (OS) were longer in high-grade cTNBC than in high-grade sTNBC (P=0.091 and 0.518), and were longer in low-grade sTNBC than in high-grade sTNBC (P=0.051 and 0.350). Metaplastic carcinomas showed larger tumor size (P=0.008) and higher proliferative Ki67 index (P=0.004) than cTNBCs.ConclusionsResults from our cohort imply that sub-categorization or subtyping and histological grading could be meaningful in pathological evaluation of TNBC, and need to be clarified in more large collections of TNBC.

Non-Ductal Tumors of the Pancreas.

Non-ductal tumors of the pancreas are relatively rare tumors and include pancreatic neuroendocrine tumors (PanNETs), poorly differentiated neuroendocrine carcinomas, acinar cell carcinoma, solid pseudopapillary neoplasm, and pancreatoblastoma. These tumors have a morphology and biology that is distinct from that of ductal neoplasms of the pancreas. PanNETs are the most common tumors among this group. A brief summary of each tumor is described here with an emphasis on the clinical presentation, cytological features, tumor histology, and immunohistochemical profile. Differential diagnoses for each entity are also discussed.

Pictorial Review of Rare Pancreatic Tumors and Tumor-Like Lesions

췌장에는 다양한 종류의 종양 및 종양 유사 병변들이 생길 수 있다. 이 가운데, 췌장선암은 췌장의 가장 흔한 종양으로서 일반적으로 췌장암이라고 하면 이 종양을 가리킨다. 최근에는 영상 검사의 기술적 진보와 이용이 증가하면서 췌장의 희귀 종양 및 종양 유사 병변들의 발견 빈도가 증가하고 있다. 췌장의 드문 종양 및 종양과 유사한 병변들은 치료 방침과 예후가 췌장선암과 다르기 때문에 이들 질환의 감별은 임상적으로 중요한 의의가 있다. 영상 검사는 포상세포암이나 신경초종 등의 희귀 종양 및 자가면역 췌장염 또는 염증성 거짓종양과 같은 종양 유사 병변들과 췌장선암의 감별 진단에 중요한 역할을 하지만 영상 소견만으로 이들 질환을 정확히 구분하는 것은 한계가 있다. 이 논문에서는 췌장에서 생길 수 있는 희귀 종양 및 종양 유사 병변들의 다양한 영상 소견들과 췌장선암과의 감별에 있어 도움이 되는 특징들을 제시하고자 한다.

Management of salivary gland tumours at a tertiary care hospital

Endogenous hormones have been reported in normal and neoplastic salivary glands, but some of the results have been conflicting. Estrogen receptors were found in nearly 80% of normal glands in males and females and four out of eight salivary tumours in women had estrogen receptor levels similar to those of “hormonally dependent” breast carcinomas. However, more recent studies have not confirmed this finding and questioned the methodology. Estrogen receptors have been reported in a minority of cases of acinic cell carcinoma, mucoepidermoid carcinoma and salivary duct carcinoma, but were not detected in adenoid cystic carcinoma.Estrogen or estrogen receptors have been reported in pleomorphic adenomas in some studies, but in others, estrogen receptors were absent. Progesterone receptors have been reported in normal salivary gland. After evaluation of the tumor by clinical examination and specific investigations, a surgical plan was formulated. The final decision was taken per operatively by the surgeon. The specimen was sent for HPE. Overall pleomorphic adenoma, constitute 80% of all salivary gland tumours. In parotid it constitutes 77.77% of all tumours occurring in parotid gland. Among malignant tumours sqamous cell carcinoma constitute 5% and myoepithelial tumour constitutes 5% of all tumours occuring in salivary glands. One HPR was normal accounting for 5% and one was haemangioma.

EPIDEMIOLOGY MAJOR SALIVARY GLAND TUMOUR IN EASTERN INDONESIA

Introduction: Salivary glands tumours are relatively rare to find. There is still no adequate data about the incidence of salivary gland tumours in Eastern Indonesia. The main objective of this research was to evaluate the patient profile, location of tumour, histopathology, and management of salivary glands tumours. Methods: Descriptive retrospective used from January 2014 to December 2018, patients in Eastern Indonesia. Results: There are 47 patients with salivary glands tumours. Females were 55,3% and male were 44,7%. By age groups found that 60 years for 27,7%. Based on the histopathology classification, pleomorphic adenoma for 34%, Whartin tumour for 2.1%, mucoepidermoid carcinoma for 29,8%, adenocarcinoma for 6,4%, Acinic cell carcinoma for 6,4%. Cystic adenoid for 6,4%, Epithelial carcinoma for 14,8%. Based on the location of the tumour’s appearance, parotid gland for 85,1%, sub-mandibular gland for 8,6%, sublingual glands for 6,3%. Based by the incidences, first year for 25,5%, second year for 12,8%, third year for 21,3%, fourth year for 12,8%, fifth year for 27,6%. Conclusion: Salivary gland tumours in our institution more common in women, developed in people aged 31-45 years, the parotid gland is the most common site and the most common malignant tumours are mucoepidermoid carcinoma.

Cytological Diagnosis of Acinic Cell Carcinoma. A Study of Four Cases with Emphasis on Differential Diagnosis and DOG1 Expression.

Cytological Diagnosis of Acinic Cell Carcinoma. A Study of Four Cases with Emphasis on Differential Diagnosis and DOG1 Expression.

Acinic Cell Carcinoma of the Major Salivary Glands: Analysis of Prognostic Factors in 2,950 Patients

Acinic Cell Carcinoma of the Major Salivary Glands: Analysis of Prognostic Factors in 2,950 Patients

Pancreatic Neoplasms With Acinar Differentiation: A Review of Pathologic and Molecular Features.

Pancreatic acinar lesions encompass a broad spectrum of malignant tumors and benign reactive processes affecting both adults and children, with clinical, pathologic, and molecular features that are distinct from more common ductal neoplasms. Accurate morphologic diagnosis and molecular assessment of these uncommon neoplasms is critical for effective patient care. To review the clinical, pathologic, and molecular features of pancreatic neoplasms with acinar differentiation, the most common of which is acinar cell carcinoma but which also includes mixed carcinomas with acinar components, cystic acinar lesions, and pancreatoblastoma. We assessed the current primary literature, as well as recently updated diagnostic manuals. Pancreatic acinar neoplasms are a morphologically and molecularly heterogeneous group of diseases that are characterized by acinar differentiation of at least a subset of the neoplastic cells, defined either morphologically (granular cytoplasm, single prominent nucleoli) or immunohistochemically. Squamoid nests are a key morphologic feature of pancreatoblastoma. Alterations in WNT signaling and chromosomal 11p loss are common molecular features of both acinar cell carcinoma and pancreatoblastoma. Targetable molecular alterations in acinar carcinoma include BRAF rearrangements and DNA repair defects, including mismatch repair deficiency and BRCA pathway defects. For practicing pathologists, morphologic recognition of such acinar neoplasms is critical, and in the future, molecular diagnostics to identify lesions susceptible to targeted therapy will likely form an important component of patient care.

SECRETORY CARCINOMA OF SALIVARY GLANDS: WHERE ARE WE?

Secretory carcinoma, described as mammary analog secretory carcinoma, is a recently described tumor of salivary glands that is defined by its histologic, immunophenotypic, and genetic similarities to the secretory breast carcinoma and is characterized by ETV6 translocation. The first description of mammary analog secretory carcinoma was reported by Skalova et al. in 2010. Retrospective studies showed that some tumors of salivary glands such as acinic cell carcinoma, low-grade salivary duct carcinoma, adenocarcinoma/cystadenocarcinoma not otherwise specified (NOS), and low-grade mucoepidermoid carcinoma were misdiagnosed. The purpose of this study is to review the literature showing the differential characteristics among these tumors and secretory carcinoma, highlighting how to perform the correct diagnosis, giving the patients the right treatment and improving their prognosis. Potential target therapy is also approached.

PAPILLARY CYSTADENOCARCINOMA: A CASE REPORT

Papillary cystadenocarcinoma (PCC) is a rare malignant tumor of the salivary glands featured by cysts and papillary endocystic projections. The differential diagnosis includes cystadenoma, papillary-cystic variant of acinic cell carcinoma polymorphous low-grade adenocarcinoma (PLGA), salivary duct carcinoma, and adenoid cystic carcinoma (ACC). Nuclear pleomorphism, mitosis, and infiltrative growth pattern affirm the malignancy of PCC. A 66-year-old man presented with a swelling in the upper alveolar ridge and hard palate. Intraorally, an exophytic, friable and ulcerated lesion was observed. Computed tomography scan showed a large soft tissue mass destroying the left maxilla. An incisional biopsy was performed. Based on the histopathologic features of papillary projections extending into the cystic lumen, the diagnosis of PCC was confirmed. The patient was referred to an oncology center where chemotherapy and radiotherapy were chosen as the appropriate treatment. Currently, no signs of recurrence were detected after 2 years of clinical follow-up. Papillary cystadenocarcinoma (PCC) is a rare malignant tumor of the salivary glands featured by cysts and papillary endocystic projections. The differential diagnosis includes cystadenoma, papillary-cystic variant of acinic cell carcinoma polymorphous low-grade adenocarcinoma (PLGA), salivary duct carcinoma, and adenoid cystic carcinoma (ACC). Nuclear pleomorphism, mitosis, and infiltrative growth pattern affirm the malignancy of PCC. A 66-year-old man presented with a swelling in the upper alveolar ridge and hard palate. Intraorally, an exophytic, friable and ulcerated lesion was observed. Computed tomography scan showed a large soft tissue mass destroying the left maxilla. An incisional biopsy was performed. Based on the histopathologic features of papillary projections extending into the cystic lumen, the diagnosis of PCC was confirmed. The patient was referred to an oncology center where chemotherapy and radiotherapy were chosen as the appropriate treatment. Currently, no signs of recurrence were detected after 2 years of clinical follow-up.