Near complete remission of an inoperable pancreatic acinar cell carcinoma after BRAF-/MEK-inhibitor treatment-A case report and review of the literature.

INTRODUCTION: Pancreatic acinar cell carcinomas are rare malignant neoplasms. High-quality evidence about the best treatment strategy is lacking. We present the case of a 52-year-old male with a BRAFV600E -mutated PACC who experienced a complete remission after chemotherapy with BRAF-/MEK-inhibitors. CASE: The patient presented with upper abdomen pain, night sweat, and weight loss. CT scan showed a pancreatic tumor extending from the pancreas head to body. Histological workup identified an acinar cell carcinoma. As the tumor was inoperable, chemotherapy with FOFIRNIOX was initiated and initially showed a slight regression of disease. The regimen had to be discontinued due to severe side effects. Molecular analysis identified a BRAFV600E mutation, so the patient was started on BRAF- and MEK-inhibitors (dabrafenib/trametinib). After 16 months, CT scans showed a near complete remission with a markedly improved overall health. DISCUSSION: Studies suggest that up to one-fourth of PACCs carry a BRAF mutation and might therefore be susceptible to a BRAF-/MEK-inhibitor therapy. This offers a new therapeutic pathway to treat this rare but malignant neoplasm.

Clinical and histopathological parameters in transrectal ultrasound-guided biopsies associated with tumor upgrading after radical prostatectomy: A comparative analysis of risk groups.

BACKGROUND: Thanks to technological advances, prostate cancer (PCa) can be diagnosed at a younger age. It is known that most of these patients are in the low-intermediate risk group, and the histological grade of the tumor increases in half of those undergoing radical prostatectomy (Rp) compared to their diagnostic biopsies. This is especially important in terms of active surveillance (AS) and/or the timely evaluation of curative treatment options in patients diagnosed at an early age. Our aim was to investigate clinical and histopathological parameters that may be associated with an increase in the histological grade of the tumor in patients with acinar adenocarcinoma who were diagnosed by transrectal ultrasound-guided biopsy (TRUS-Bx) and underwent Rp. METHODS: A total of 205 patients with classical acinar adenocarcinoma diagnosed by TRUS-Bx without metastasis and who underwent Rp were grouped according to the D'Amico risk classification. Age at diagnosis, serum prostate-specific antigen (PSA), PSA density, prostate volume, Prostate Imaging Reporting and Data System (PI-RADS) score, clinical stage, Gleason Grade Group (GGG), high-grade intraepithelial neoplasia in tumor-free cores (HGPIN) (single and ≥2 cores), perineural invasion (PNI), and lymphovascular invasion (LVI) was obtained. Additionally, GGG, pathological stage, lymph node metastasis, surgical margin positivity, and tumor volume obtained from Rp were evaluated. Comparisons were made between the case groups in which the tumor grade increased and remained the same, in terms of age, serum PSA, PSA density, HGPIN in tumor-free cores (single and ≥2 cores), PNI, and LVI in all biopsies (with or without tumors), as well as risk groups. In addition, the relationships of HGPIN in tumor-free cores (single and ≥2 cores), PNI, and LVI on TRUS-Bx with age, serum PSA and PSA density, tumor volume, surgical margin positivity, pathological stage, lymph node metastasis, and risk groups were examined separately. RESULTS: Of the patients, 72 (35.1%) were in the low-risk group, 95 (46.3%) in the intermediate-risk group, and 38 (18.5%) in the high-risk group. Most of the patients with an increased histological grade (n = 38, 48.1%) were in the low-risk group (p < 0.05) and had an advanced median age. HGPIN in single and ≥2 tumor-free cores and PNI were more common in these patients (p < 0.01, p < 0.001, and p < 0.05, respectively). According to the multivariable analysis, advanced age (odds ratio [OR]: 1.087, 95% confidence interval [CI]: 1.029-1.148, p < 0.05), high serum PSA (OR: 1.047, 95% CI: 1.006-1.090, p < 0.05), HGPIN in ≥2 tumor-free cores (OR: 6.346, 95% CI: 3.136-12.912, p < 0.001), and PNI (OR: 3.138, 95% CI: 1.179-8.356, p < 0.05) were independent risk factors for a tumor upgrade. Furthermore, being in the low-risk group was an independent risk factor when compared to the intermediate- and high-risk groups (OR: 0.187, 95% CI: 0.080-0.437, p < 0.001 and OR: 0.054, 95% CI: 0.013-0.230, p < 0.001, respectively). The HGPIN diagnosis was more common in the low- and intermediate-risk groups. Advanced age at diagnosis, high serum PSA and PSA density values were associated with PNI on TRUS-Bx. High serum PSA and PSA density values were associated with LVI on TRUS-Bx. Surgical margin positivity was higher in cases with PNI and LVI detected by TRUS-Bx. HGPIN in ≥2 tumor-free cores, PNI, and LVI on TRUS-Bx were associated with a higher rate of lymph node metastases. CONCLUSIONS: In patients diagnosed with acinar adenocarcinoma, the presence of HGPIN even in a single tumor-free core on TRUS-Bx was found to be significant in terms of showing an increase in the histological tumor grade in Rp. The diagnosis of HGPIN in ≥2 tumor-free cores on TRUS-Bx was determined as an independent risk factor for an increased Gleason score after Rp. Furthermore, an advanced age, a high serum PSA value, being in the low-risk group, and the presence of PNI were associated with a tumor upgrade. HGPIN in ≥2 tumor-free cores, PNI, and LVI were also associated with lymph node metastasis. Therefore, the diagnosis of HGPIN should be signed out on pathological reports.

Recent developments in the pathology of primary pulmonary salivary gland-type tumours.

Primary pulmonary salivary gland-type tumours are rare neoplasms that are thought to arise from seromucinous glands that are located in the submucosa of large airways. These neoplasms have clinical and pathologic features that are distinct from other pulmonary neoplasms. The majority of primary pulmonary salivary gland-type tumours are malignant, with the most common entities being mucoepidermoid carcinoma, adenoid cystic carcinoma, and epithelial-myoepithelial carcinoma. Less commonly seen are myoepithelial carcinoma, hyalinizing clear cell carcinoma, acinic cell carcinoma, secretory carcinoma, salivary duct carcinoma, intraductal carcinoma, and polymorphous adenocarcinoma. Benign salivary gland-type tumours of the lung include pleomorphic adenoma and sialadenoma papilliferum. Morphologic, immunophenotypic, and molecular features of these neoplasms are largely similar to salivary gland tumours elsewhere, and therefore the exclusion of metastatic disease requires clinical and radiologic correlation. However, the differential diagnostic considerations are different in the lung. The distinction of salivary gland-type tumours from their histologic mimics is important for both prognostication and treatment decisions. Overall, salivary gland type-tumours tend to have a more favourable outcome than other pulmonary carcinomas, although high-grade variants exist for many of these tumour types. Recent advances in our understanding of the spectrum of salivary gland-type tumours reported in the lung and their diversity of molecular and immunohistochemical features have helped to refine the classification of these tumours and have highlighted a few differences between salivary gland-type tumours of the lung and those primary to other sites.

Successful immunotherapy with PD-1 Iinhibitor for advanced pancreatic cancer: report of two cases and review of literature.

Pancreatic cancer is a highly malignant tumor, and most patients are diagnosed at an advanced stage. Unfortunately, due to the immunosuppressive tumor microenvironment of pancreatic cancer, the benefits of immunotherapy for patients with advanced pancreatic cancer are still unclear. Here, we present two cases of advanced pancreatic cancer being controlled by immunotherapy, with pathological diagnoses of ductal adenocarcinoma and acinar cell carcinoma, respectively. Next-generation sequencing (NGS) of both patients is high tumor mutation burden (tumor mutation burden-High) and microsatellite stable. The patient with pancreatic ductal adenocarcinoma was diagnosed as a locally advanced disease (stage III). She received irreversible electroporation, used the programmed death receptor-1 (PD-1) inhibitor (pembrolizumab) combined with chemotherapy (S-1), and then used only the PD-1 inhibitor as a maintenance treatment. As a result, the patient's lesion was significantly reduced, with a partial response time of up to 31 months. The patient with acinar cell carcinoma was diagnosed as a metastatic disease (stage IV), next-generation sequencing revealed mutations in SMAD4 and KMT2D, and two chemotherapy regimens were used unsuccessfully. Then, the combination of chemotherapy with PD-1 (tislelizumab) and vascular endothelial growth factor/vascular endothelial growth factor receptor (anlotinib) inhibitors were used, and the lesions of the patient were significantly reduced, and the progression-free survival after immunotherapy was 19 months. In advanced pancreatic cancer, a prognosis of this magnitude is rare. Our cases reveal the potential of immunotherapy as a cornerstone treatment in the management of advanced pancreatic cancer.

Comprehensive review of pancreatic acinar cell carcinoma: epidemiology, diagnosis, molecular features and treatment.

Pancreatic acinar cell carcinoma is a rare form (0.2-4.3%) of pancreatic neoplasm with unique clinical and molecular characteristics, which largely differ from pancreatic ductal adenocarcinoma. Pancreatic acinar cell carcinoma occurs more frequently in males and can occur in children. Serum lipase is elevated in 24-58% of patients with pancreatic acinar cell carcinoma. Pancreatic acinar cell carcinomas tend to be large at diagnosis (median tumour size: ~5 cm) and are frequently located in the pancreas head. Radiologically, pancreatic acinar cell carcinoma generally exhibits a solid appearance; however, necrosis, cystic changes and intratumoral haemorrhage can occur in larger lesions. Immunostaining is essential for the definitive diagnosis of pancreatic acinar cell carcinoma. Compared with pancreatic ductal adenocarcinoma, pancreatic acinar cell carcinoma has a more favourable prognosis. Although radical surgery is recommended for patients with pancreatic acinar cell carcinoma who do not have distant metastases, the recurrence rate is high. The effectiveness of adjuvant therapy for pancreatic acinar cell carcinoma is unclear. The response to FOLFIRINOX is generally favourable, and some patients achieve a complete response. Pancreatic acinar cell carcinoma has a different genomic profile compared with pancreatic ductal adenocarcinoma. Although genomic analyses have shown that pancreatic acinar cell carcinoma rarely has KRAS, TP53 and CDKN2A mutations, it has a higher prevalence of homologous recombination-related genes, including BRCA1/2 and ATM, than pancreatic ductal adenocarcinoma, suggesting high sensitivity to platinum-containing regimens and PARP inhibitors. Targeted therapies for genomic alternations are beneficial. Therefore, genetic testing is important for patients with pancreatic acinar cell carcinoma to choose the optimal therapeutic strategy.

Salivary gland-type cancers: cross-organ demographics of a rare cancer.

BACKGROUND: Salivary gland-type cancers (SGTCs) are histologically heterogeneous and can affect organs other than the salivary glands. Some tumors outside the salivary glands are diagnosed on their unique histological characteristics. Comprehensive cross-organ studies on SGTCs are limited. METHODS: We retrospectively analyzed the data of patients with salivary duct carcinoma (SDC), adenoid cystic carcinoma (AdCC), mucoepidermoid carcinoma (MEC), epithelial-myoepithelial carcinoma (EMC), acinic cell carcinoma (AcCC), and polymorphous adenocarcinoma (PAC) who visited our institution between 2009 and 2019. The primary tumor sites were classified into four categories; major salivary glands, head/neck (H/N) excluding (exc) major salivary glands (MSG) regions, broncho-pulmonary regions, and "others". H/N exc MSG was further divided into three subcategories, nasal/paranasal sinus, oral and pharynx/larynx. RESULTS: We identified 173 patients with SGTCs, with SDC, AdCC, MEC, EMC, AcCC, and PAC accounting for 20%, 42%, 27%, 3%, 8%, and 1% of the cases, respectively. The most frequent primary site was the major salivary glands (64%), followed by H/N exc MSG regions (27%), broncho-pulmonary regions, and "others", thus non-salivary gland origins accounted for 9% of all cases. Patients with SDC, MEC, AcCC, or SGTC of the major salivary glands and broncho-pulmonary regions were more frequently treated by surgery. The overall survival time of the patients with MEC was significantly better than that of patients with SDC or EMC. CONCLUSIONS: This cross-organ study highlights the clinical significance of SGTCs, underscoring the need for developing novel therapies for this rare disease entity.

[Effectiveness of minimally invasive surgery in the treatment of pancreatic acinar cell carcinoma].

Objective: To explore the effectiveness of minimally invasive surgical treatment for pancreatic acinar cell carcinoma (PACC). Methods: Six patients with PACC diagnosed in Peking University Third Hospital from January 2010 to September 2022 were retrospectively selected. Preoperative evaluation was performed on whether the lesions were eligible for surgery, including whether radical resection of liver metastases could be performed. Laparoscopic or Da Vinci robot-assisted resection was performed on six patients, and spleen retention was determined according to the original lesions and the relationship with peripheral blood vessels and tissues, while simultaneous resection was performed on cases of peripheral organ tissue invasion. The patients' basic information, preoperative general conditions, preoperative diagnosis and tumor stage, minimally invasive surgery methods, postoperative complications, pathological results, tumor stage and follow-up data were collected and analyzed to explore the effectiveness of minimally invasive surgery. Results: Among the six patients, four were males and two were females, with the age of 25-69 years. Five patients had abdominal pain and distension before surgery, five patients had tumors located at the tail of the pancreatic body, and one patient had tumors located at the head of the pancreas. Preoperative imaging (enhanced CT and MRI) was performed to measure the tumor diameter (2.8-10.0 cm). Tumor markers were elevated in two patients before surgery, and six patients underwent surgery through laparoscopy or robotic platform. No complications such as postoperative pancreatic fistula and bleeding were clinically relevant during and after surgery. There were two cases with concurrent or heterochronous liver metastasis, two cases with lymph node metastasis and nodular metastasis, four cases with tumor invasion of surrounding organs (stomach, spleen or duodenum), and three cases with vascular cancer thrombi. The follow-up time of the six patients was 12 to 165 months, and one patient underwent three operations due to postoperative liver metastasis and residual pancreatic recurrence, and the results were satisfactory. All the six patients survived at the last follow-up. Conclusions: PACC is prone to invade the surrounding organs, and has a large tumor diameter. Radical surgery for PACC can be completed through minimally invasive surgery, and satisfactory oncology prognosis can be obtained. In addition, some PACC patients with recurrence and metastasis can still be treated by surgery.

[Amplifiation of the c-MYC gene in acinar prostate adenocarcinoma. Morphogenic comparisons]. / Amplifikatsiya gena c-MYC pri atsinarnoi adenokartsinome prostaty. Morfogeneticheskie sopostavleniya.

OBJECTIVE: The purpose of this work was to evaluate c-MYC gene amplification in the substrate of prostate acinar adenocarcinoma at various Gleason scores and various stages of the disease, taking into account the morphological characteristics of the tumor. MATERIAL AND METHODS: The number of cases in the study was 82, including the control group - 12 cases. Morphological assessment included: determination of the total Gleason score, grading group, assessment of lymphovascular/perineural invasion, and architectural characteristics of the tumor. Gene amplification was assessed by FISH using the c-MYC (8q24)/SE8 probe. RESULTS: In all cases of the study group, amplification of the c-MYC gene was detected in the tumor, with a significant difference from the control group (p<0.05). When assessing cases with 4-6 fold copies of the gene, significant differences were established between patients with stages II and III of the disease and stage IV (10.0 and 13.5 versus 30.0) (p<0.05). Cluster amplification of the c-MYC gene was detected with equal frequency in groups of patients with stages III and IV of the disease, while in stage II of the disease, the event almost did not occur (p<0.05). A significant increase in the level of c-MYC gene amplification was found in groups with advanced stages of the disease (p<0.02). Non-cluster amplification significantly distinguishes T4M0 and T4M1 stage patients from the rest with a significant increase in the score (p<0.05). In the metastatic stage of the disease, there was an increase c-MYC gene amplification compared to the non-metastatic stage (p<0.02). The copy number of the c-MYC gene was significantly higher in cases with perineural and lymphovascular invasion, as well as in cases of cribriform tumor organization (p<0.05). CONCLUSION: Amplification of the c-MYC gene in prostate tumor cells is associated with advanced stages of the disease (T4M0 and T4M1) with an increase in the copy number of the gene during the metastatic stage of the process. It was found that increased amplification of the c-MYC gene distinguishes groups of patients whose tumors exhibit perineural and lymphovascular invasion, as well as a cribriform pattern of tumor organization.

[Pancreatic Acinar Cell Carcinoma with Peritoneal Recurrence Treated with Peritonectomy and Intraoperative Hyperthermic Intraperitoneal Chemotherapy-A Case Report].

A 31-year-old man with a big epigastric mass from pancreas body was completely removed by distal pancreatectomy and segmental gastrectomy. Two years after oral administration of S-1 for 4 courses, peritoneal dissemination on the right subdiaphragmatic space was detected. Laparotomy revealed white colored round nodules were found scattered on the peritoneal surface, and the peritoneal cancer index(PCI)was 18. To achieve complete resection of peritoneal nodules, peritonectomy was performed. After complete removal of macroscopic peritoneal metastasis(PM), intraoperative hyperthermic intraoperative peritoneal chemotherapy using 1 gr of gemcitabine and 60 mg of docetaxel was performed for 40 min with thermal dose of 41.5 min. Postoperative course was uneventful. Drug sensitivity test(HDRA method)showed that gemcitabine that gemcitabine showed the highest inhibition rate. The patient was treated with systemic gemcitabine chemotherapy. He is still alive without recurrence 18 months after peritonectomy plus intraoperative HIPEC. Pathological examination showed pancreatic acinar cell carcinoma(PACC)demonstrating positive for chymotrypsin. In conclusion, we present a PACC-case with PM successfully treated by a comprehensive treatment. Intraoperative HIPEC using gemcitabine may be effective for PACC patients with PM in treating residual micrometastasis after peritonectomy.

Ductal Adenocarcinoma of the Prostate with Novel Genetic Alterations Characterized by Next-Generation Sequencing.

Ductal adenocarcinoma of the prostate (DAP) is an uncommon variant of prostate cancer associated with aggressive disease and poor outcome. It presents most frequently as a mixed tumor combined with acinar adenocarcinoma. Although the histopathological features of DAP are well known, its genomic characteristics are still evolving, prompting the suggestion that all DAP would benefit from molecular analysis with the purpose of improving tumor recognition, genetic classification, and, ultimately, personalized therapy. Herein, we report a case of DAP with novel genetic alterations (BCOR P1153S, ERG M219I, KDR A750E, POLE S1896P, and RAD21 T461del).

Complete pathological response to pembrolizumab in pretreated pancreatic acinar cell carcinoma.

BACKGROUND: Therapeutic approach used for pancreatic ductal adenocarcinoma is usually translated also for the rarer acinar counterpart, which shows a different mutational landscape nevertheless. While dMMR/MSI-H status is rare in the ductal histotype, it appears to be more prevalent in pancreatic acinar cell carcinoma (PACC). CASE PRESENTATION: We report the case of a patient with locally advanced MSI-H PACC in whom the treatment with the anti-PD-1 pembrolizumab, administered as third line, made possible surgical resection, achieving even an exceptional pathological complete response. CONCLUSIONS: Treatment of PACC should be tailored based on the peculiar molecular features that distinguish PACC from ductal adenocarcinoma. Evaluation of potentially therapeutically targetable alterations should be mandatory in case of PACC diagnosis.

Successful endotracheal intervention for primary tracheal acinic cell carcinoma: A case report and literature review.

INTRODUCTION: Primary tracheal acinic cell carcinoma (ACC) is an exceptionally rare malignancy, posing challenges in understanding its clinical behavior and optimal management. Surgical resection has traditionally been the primary treatment modality, but we present a compelling case of tracheal ACC managed with endotracheal intervention, challenging conventional approaches. PATIENT CONCERNS: A 53-year-old woman presented with shortness of breath, cough, and hemoptysis. Enhanced computed tomography revealed an obstructive tracheal lesion, leading to her referral for further assessment. DIAGNOSIS: Microscopic evaluation, immunohistochemistry, and clinical assessments confirmed primary tracheal ACC, an exceedingly rare condition with limited clinical insights. INTERVENTIONS: We utilized rigid bronchoscopy to perform endotracheal intervention, successfully resecting the tumor and restoring tracheal patency. Postoperatively, the patient received no radiotherapy or chemotherapy. OUTCOMES: The patient achieved complete recovery, with 24-month follow-up examinations indicating no recurrence or metastatic disease. Only minimal scar tissue remained at the resection site. CONCLUSION: This case demonstrates the potential of endotracheal intervention as a curative approach for primary tracheal ACC, minimizing invasiveness and preserving tracheal function. Collaborative research efforts and extensive case reporting are crucial for advancing our understanding of this rare malignancy and optimizing treatment strategies for improved patient outcomes.

Acinic cell Carcinoma with high-grade Squamoglandular and Chondrosarcomatous Transformation Mimicking 'Carcinosarcoma ex-pleomorphic Adenoma': A Wrinkle in the Proposed Nomenclature Revision for Sarcomatoid Salivary Gland Neoplasms.

While acinic cell carcinoma (AciCC) can undergo high-grade transformation (HGT) to high-grade adenocarcinoma or poorly differentiated carcinoma, other morphologies such as spindle cell/sarcomatoid carcinoma are rare and not well-characterized. We herein report a novel case of AciCC with squamoglandular and chondrosarcomatous HGT mimicking a so-called 'carcinosarcoma ex-pleomorphic adenoma'. The patient is an 81-year-old male with a two-month history of neck swelling and referred otalgia who presented with a left parapharyngeal space mass extending into retropharyngeal space and pterygoid muscles. On resection, the tumor showed considerable morphologic diversity with high-grade serous and mucous acinar components as well as cribriform to solid apocrine-like components with comedonecrosis and squamous differentiation, all of which were embedded in a chondromyxoid background ranging from paucicellular and bland to a high-grade chondrosarcoma/pleomorphic sarcoma-like appearance. Only a minor conventional AciCC component was noted. Immunostains were negative for AR and only focally positive for GCDFP-15 arguing against a true apocrine phenotype, while PLAG1 and HMGA2 were negative arguing against an antecedent pleomorphic adenoma. On the other hand, SOX-10, DOG-1 and PAS after diastase highlighted serous acinar differentiation, and mucicarmine, and NKX3.1 highlighted mucous acinar differentiation. NR4A3 immunohistochemical staining and NR4A3 fluorescence in situ hybridization were positive in the carcinomatous and sarcomatoid components while sequencing analysis of both components revealed identical alterations involving TP53, PIK3CB, ARID1A, and STK11. This unique case warrants caution in designating all salivary sarcomatoid carcinomas with heterologous elements as part of the 'carcinoma ex-pleomorphic adenoma' family.

Long-term survival after systemic chemotherapy, chemoradiotherapy, and maintenance therapy for an older adult patient with recurrent pancreatic acinar cell carcinoma.

Pancreatic acinar cell carcinoma (PACC) is a rare cancer with no specific treatment. The treatment and chemotherapy for PACC are selected according to pancreatic ductal adenocarcinoma (PDAC). Herein, we describe a recurrent PACC case of an older adult patient. The patient was treated with systemic chemotherapy, chemoradiotherapy, and maintenance therapy based on the pathologic germline BRCA2 variant, resulting in long-term survival. The pathogenic BRCA variant is detected more frequently in patients with PACC than in those with PDAC. The BRCA variant significantly impacts treatment selection and prognosis; therefore, early genomic analysis is recommended when treating PACC.

The response of pancreatic acinar cell carcinoma to platinum and olaparib therapy in a germline BRCA2 variant carrier: case report and literature review.

A 73-year-old Japanese man with a history of distal biliary cancer treated by pancreatoduodenectomy developed pancreatic acinar cell carcinoma (PACC) treated by remnant pancreatectomy and adjuvant chemotherapy. Thirteen months after surgery, multiple liver metastases developed and FOLFOX chemotherapy was initiated. Based on the PACC diagnosis and a positive family history for breast and ovarian cancer genetic testing was performed which revealed a pathogenic germline BRCA2 variant (c.8629G > T, p.Glu2877Ter). Olaparib therapy was initiated and the metastases responded well (partial response). PACC is a BRCA2-associated cancer which may respond well to PARP inhibitors.

Cancer-associated stroke from progressive acinic cell carcinoma.

Cancer-associated stroke is an evolving subgroup of embolic strokes of undetermined source. A man in his mid-20s with progressive follicular variant acinic cell carcinoma of the parotid was admitted because of new onset left-sided weakness. Neuroimaging confirmed a right middle cerebral artery infarction. After extensive diagnostics, stroke aetiology was deemed from cancer-induced hypercoagulability. Questions which arose regarding his management included (1) What was the best antithrombotic for secondary stroke prevention? (2) What was his risk for intracranial or tumorous bleeding once antithrombotics had been started? (3) How many days post-stroke could the antithrombotic be initiated? and (4) When could he be cleared for palliative chemotherapy and whole brain irradiation? The approach to address the abovementioned questions in the management of a rare cancer complicated by stroke is presented. Although treatments are guided by known pathomechanisms, additional studies are needed to further support current treatment strategies for this subgroup of patients.

Elucidating the nature of acinic cell carcinoma of the breast with high-grade morphology: evidence from case report.

BACKGROUND: Acinic cell carcinoma (AciCC) of the breast is a rare subtype of breast cancer. It was considered a low-grade triple-negative breast cancer (TNBC) with the potential to progress or transform into a high-grade lesion because of the molecular similarities with conventional aggressive TNBC in several genetic studies. Microscopically, the coexistence of classical low-grade and high-grade triple-negative components in breast AciCC is not uncommon. However, there is a scarcity of research on the comparative histopathological and genetic aspects of both components. CASE PRESENTATION: A 34-year-old woman with a nontender mass in the upper outer quadrant of the left breast was initially diagnosed with a malignant small round cell tumor (undifferentiated or poorly differentiated carcinoma) based on a preoperative biopsy, which was later identified as breast AciCC with a high-grade solid component. Left breast-conserving surgery with sentinel lymph node biopsy was performed. Microscopically, the breast AciCC consisted of a classical acinic component and a high-grade component. The latter demonstrated a solid sheet-like pattern characterized by large, round, pleomorphic or vesicular nuclei, prominent nucleoli, and frequent mitotic activities. Classical acinic architectures focally merged together to form solid nests and transited into high-grade areas. Remarkably, in the high-grade lesion, conventional immunochemical markers for breast AciCC, such as α1-antitrypsin (AAT), Lysozyme (LYS), Epithelial membrane antigen (EMA), S100 protein (S100), and cytokeratin (CK) were negative, whereas cell cycle protein D1 (cyclin D1) and vimentin showed diffuse expression. Next­generation sequencing (NGS) revealed that 43.5% of variants were identical in both components. Furthermore, PAK5 mutation; copy number (CN) loss of CDH1, CHEK1, and MLH1; and CN gains of CDK6, HGF, and FOXP1 were identified in the high-grade lesion. The patient was treated with eight cycles of adjuvant chemotherapy (epirubicin combined with cyclophosphamide) and radiotherapy after surgery, and she is currently alive for 43 months with no metastases or recurrences. CONCLUSIONS: This case demonstrates a comparative analysis of the histopathological and genetic characteristics of classical low-grade and high-grade components of AciCC within the same breast. This information may serve as a morphological and molecular basis for further investigation into the molecular mechanisms underlying high-grade lesions in breast AciCC.

Prognosis of primary breast salivary gland-type carcinoma: a propensity score-matching analysis with invasive carcinoma of no special type based on the SEER database for years 2010-2020.

BACKGROUND: Primary breast salivary gland-type carcinoma has weak evidence to support its management due to its rare occurrence and limited data regarding its clinicopathological features and prognosis. Therefore, this study aimed to assess clinicopathological features and prognosis for this type of carcinoma diagnosed over the past decade and compared those to the common breast invasive carcinoma of no special type (NST). METHODS: This study used the Surveillance, Epidemiology, and End Results (SEER) database to extract data regarding primary breast salivary gland-type carcinoma. Using a propensity score-matching approach, the prognosis was compared with invasive carcinoma, NST. RESULTS: This study included 488 cases of salivary gland-type carcinoma and 375,660 cases of invasive carcinoma, NST, giving an occurrence ratio of 1 to 770. Adenoid cystic carcinoma (81%) formed the majority of salivary gland-type carcinoma, followed by secretory carcinoma (13%). For salivary gland-type carcinoma, acinic cell carcinoma histological type, tumor grade 3, HER2-overexpressed status, and higher AJCC stage groups were significant worse prognostic factors for breast cancer-specific survival in univariate analyses (p < 0.05). Nonetheless, tumor grade 3 and higher AJCC stage groups remained as significant independent prognostic factors in multivariate analysis (p < 0.05). The apparent better breast cancer-specific survival of salivary gland-type carcinoma as compared to that of invasive carcinoma, NST, was diminished following adjustment for differences in baseline clinicopathological features and treatment-related variables. CONCLUSIONS: This study suggests that when managing primary breast salivary gland-type carcinoma, greater emphasis should be given to the tumor grade and AJCC stage group in addition to acinic cell carcinoma histological type and HER2 overexpression. Conventional prognostic factors are important as salivary gland-type carcinoma had similar prognosis as invasive carcinoma, NST, following adjustment for confounding variables.