Unveiling the Genomic Landscape of Intraductal Carcinoma of the Prostate Using Spatial Gene Expression Analysis.

Intraductal carcinoma of the prostate (IDCP) has recently attracted increasing interest owing to its unfavorable prognoses. To effectively identify the IDCP-specific gene expression profile, we took a novel approach of characterizing a typical IDCP case using spatial gene expression analysis. A formalin-fixed, paraffin-embedded sample was subjected to Visium CytAssist Spatial Gene Expression analysis. IDCP within invasive prostate cancer sites was recognized as a distinct cluster separate from other invasive cancer clusters. Highly expressed genes defining the IDCP cluster, such as MUC6, MYO16, NPY, and KLK12, reflected the aggressive nature of high-grade prostate cancer. IDCP sites also showed increased hypoxia markers HIF1A, BNIP3L, PDK1, and POGLUT1; decreased fibroblast markers COL1A2, DCN, and LUM; and decreased immune cell markers CCR5 and FCGR3A. Overall, these findings indicate that the hypoxic tumor microenvironment and reduced recruitment of fibroblasts and immune cells, which reflect morphological features of IDCP, may influence the aggressiveness of high-grade prostate cancer.

Brain metastases in patients with salivary duct carcinoma: A retrospective study.

BACKGROUND: Salivary duct carcinoma (SDC) is a high-grade adenocarcinoma with a 5-year survival rate of 40%. Although drug therapy has improved patients' prognosis, the impact of brain metastasis (BM) remains poorly understood. We aimed to retrospectively examine the incidence of BM in patients with SDC (n = 464) and develop a tool to estimate their prognoses. METHODS: We retrospectively examined 464 patients with SDC enrolled in a multicenter study. We investigated the incidence of BM, overall survival (OS) rates, and factors affecting prognosis in patients with BM. We also developed an SDC-graded prognostic assessment (GPA) score for disease prognostication. RESULTS: Sixty-five (14%) patients had BM. The median OS (mOS) was 13.1 months. On univariate and multivariate analyses, factors such as Eastern Cooperative Oncology Group Performance Status >1, human epidermal growth factor receptor 2-negative status, and locoregional uncontrolled disease were associated with poor OS. SDC-GPA scores according to the prognostic factors were 0, 1, 2, and 3 points, and mOS estimates were 50.5, 16.1, 3.9, and 1.2 months, respectively (p < 0.001). CONCLUSION: The SDC-GPA score emerged as a useful prognostication tool for patients with BM.

Differential expression of TRKB tyrosine kinase in the two histological types of parotid salivary duct carcinoma with cancer aggressiveness.

Parotid salivary duct carcinoma (SDC) is a rare and aggressive parotid gland carcinoma (PGC). SDC has two origins: de novo and ex pleomorphic adenoma (SDC ex PA); however, because of its rarity, the clinical and molecular features of the two types of SDC are not sufficiently understood. Here, we studied the differences in their clinicopathological and molecular features using clinical specimens while comparing them to those of adenoid cystic carcinoma (AdCC), an intermediate-grade PGC. Clinicopathological analysis of tissues from patients with PGC revealed significant associations between histological types and malignant phenotypes, including nodal metastasis, recurrence, vascular invasion, and neural invasion, and revealed more malignant phenotypes of de novo SDC than of SDC ex PA. The de novo SDC showed a significantly higher frequency of intra-neural invasion (intra-NI) and vascular invasion than AdCC and SDC ex PA. PGCs with high intra-NI were significantly correlated with malignant phenotypes and survival rates. Recently, we observed the overexpression of tropomyosin receptor kinase B (TRKB), a receptor tyrosine kinase, in PGC cells. Here, immunohistochemical and clinicopathological analyses showed that TRKB was highly expressed in SDC cells, particularly de novo SDC cells, and was significantly associated with poor survival and highly malignant phenotypes, including intra-NI and vascular invasion. Collectively, these data show that TRKB expression is significantly elevated in PGC, particularly in de novo SDC, and can be one of the biomarkers of their aggressiveness.

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).

Gastric Metastasis from Salivary Duct Carcinoma Mimicking Scirrhous Gastric Cancer.

A 59-year-old man underwent submandibular gland excision for salivary duct carcinoma (SDC). One year later, esophagogastroduodenoscopy indicated gastric diffuse mucosal thickening with luminal contraction, mimicking scirrhous gastric carcinoma. Biopsy specimens showed dense proliferation of neoplastic cells expressing androgen receptor and human epidermal growth factor 2, indicating SDC. Gastric diffuse infiltrative metastasis is generally characteristic of gastric metastasis from invasive ductal carcinoma, which shows histologic features similar to SDC. This is the first known report of gastric diffusely infiltrating metastasis in an SDC patient. Rapidly progressing, diffuse gastric wall thickening should also be considered indicative of salivary tumor-associated gastric metastasis.

Clinicopathological characteristics of four major histological types of high-grade parotid carcinoma.

OBJECTIVE: High-grade parotid carcinoma generally has a poor prognosis, and the histological type is mucoepidermoid carcinoma (MEC), salivary duct carcinoma (SDC), carcinoma ex pleomorphic adenoma (CEPA), or adenoid cystic carcinoma (AdCC) in the majority of cases. METHODS: During the 23-year period from September 1999 to December 2022, 250 patients with parotid carcinoma underwent initial treatment and had the histopathological type of their carcinoma. Retrospective study evaluated 111 MEC, SDC, CEPA, or AdCC cases among 134 patients with high-grade parotid carcinoma. We examined pathological and clinical features and prognosis, evaluated factors associated with recurrence, and performed immunohistological examinations. RESULTS: Pathological and clinical features and factors associated with recurrence were different for each histological type. The 10-year disease-free survival rates were as follows: MEC, 34.9%; SDC, 22.6%; CEPA, 47.1%; and AdCC, 56.3%. Human epidermal growth factor receptor type-2 and androgen receptor were positive in 48% and 56% of patients with SDC, respectively, 38% and 25% of those with CEPA. CONCLUSION: Each histological type has its own pathological and clinical features, recurrence types, and tumor activities, suggesting that differentiating between high-grade parotid carcinomas according to histological type will improve diagnosis, and thus prognosis.

Salivary Duct Carcinoma Arising in a Warthin Tumor of the Parotid Gland: A Rare Case Report with Review of Literature and PD-L1 Expression.

Warthin's tumor is the second most common neoplasm of the parotid gland and consists of 2 components, including lymphoid stroma and glandular epithelium. Malignant transformation in this tumor is mostly seen in the lymphoid component; however, the carcinomatous transformation of the epithelial component is extremely rare. Cases of latter reported in the literature include squamous cell carcinoma, adenocarcinoma, mucoepidermoid carcinoma, oncocytic carcinoma, Merkel cell carcinoma, and undifferentiated carcinoma. We describe an extremely rare case of salivary duct carcinoma arising in a Warthin tumor in a 64-year-old male. Patient presented with an enlarging left parotid mass, biopsy of which showed salivary duct carcinoma. He subsequently underwent left parotidectomy along with left level II-IV lymph node dissection. Histology revealed both in situ as well as invasive salivary duct carcinoma arising from Warthin tumor. Immunohistochemistry showed tumor cells positive for CK7, AR, and GATA3, while p63 highlighted the myoepithelial cell layer in the in situ component. Her2 was 2+ by immunohistochemistry. In addition, PD-L1 IHC revealed positive expression with a combined positive score of 20%.

Eccrine Ductal Carcinoma of the Eyelid.

The authors present the third example of an eccrine ductal carcinoma of the eyelid. A woman in her early 70s presented with a lesion of the central right lower eyelid margin in the vicinity where an actinic keratosis was diagnosed by biopsy 2.75 years previously. Her dermatologist and ophthalmologist monitored the area of actinic keratosis, and it was stable for 2.5 years until the area became ulcerated and thickened with the loss of eyelashes. A wedge resection disclosed a squamous cell carcinoma in situ and a separate eccrine ductal carcinoma. The eccrine ductal carcinoma had in situ tumor thickening, an eccrine duct component, and an invasive tumor infiltrating the tarsal plate and replacing the normal meibomian glands. The invasive eccrine ductal carcinoma only mildly thickened the tarsal plate and was most likely an incidental finding in a biopsy prompted by the squamous cell carcinoma in situ. The 5-year relative survival rate for malignant apocrine-eccrine tumors is approximately 97%, and our patient is alive and without evidence of local or distant tumor recurrence 5.5 years following the excision of her eyelid tumor.

Salivary Ductal Carcinoma: A Case Report.

ABSTRACT: Salivary ductal carcinoma is an extremely rare tumor located in the parotid gland. This case details a salivary ductal carcinoma within the parotid gland of a 59-year-old man and its management.

Whole-Exome Sequencing of a Case of Squamoid Eccrine Ductal Carcinoma Reveal Similarities With Cutaneous Squamous Cell Carcinoma.

ABSTRACT: Squamoid eccrine ductal carcinoma (SEDC) is a poorly documented but likely underrecognized sweat gland malignancy with significant risk for local recurrence and potential for metastasis and rare disease-related mortality. Histopathologically, the tumor demonstrates a biphasic differentiation pattern: superficially, the tumor has squamous differentiation [indistinguishable from well-differentiated cutaneous squamous cell carcinoma (cSCC)], while the deeper aspect has a more infiltrative pattern with prominent ductal differentiation. Diagnosis of SEDC relies upon histopathologic examination alone. Its pathogenesis is poorly understood, and its genomic features have yet to be described. In this article, we characterize the genomic features in a case of SEDC through whole-exome sequencing, then compare its features with cSCC and other eccrine ductal carcinomas. Whole-exome sequencing revealed 30 mutations/Mb with 21 pathogenic or likely pathogenic mutations in total, identified across 14 different genes. The genomic abnormalities identified in this case of SEDC overlap considerably with those found in cSCC but not those of other sweat gland malignancies. The clinical and histopathologic features of SEDC previously reported and the genetic features determined from this case suggest that this tumor may arise initially as a well-differentiated cSCC that subsequently undergoes divergent differentiation focally to resemble a sweat gland malignancy. Genetic analyses of additional cases are warranted to clarify this consideration.

A Case of Metastatic Submandibular Salivary Duct Carcinoma that Completely Responded to Pembrolizumab Monotherapy.

Salivary gland carcinoma is a rare cancer and has more than 20 histopathological types. Although chemotherapy has been the mainstay of treatment for unresectable carcinomas such as multiple recurrence and distant metastasis, no standard regimen is available. In this article, we report a case of poorly differentiated salivary duct carcinoma of the submandibular gland with distant metastases that was successfully treated with pembrolizumab monotherapy. A 66-year-old man became aware of a left submandibular mass 2 months before his first visit to our department. A needle biopsy at a previous hospital revealed carcinoma, not otherwise specified. The combined positive score on a programmed death ligand-1 immunohistochemistry test was 1-10%. The patient was referred to our department for further treatment. Computed tomography revealed left level II and IV neck lymphadenopathy, bilateral lung shadowing, and osteolytic changes in the 12th thoracic vertebra. Needle biopsy showed poorly differentiated carcinoma, positive human epidermal growth factor receptor 2, and positive androgen receptor, which suggested salivary duct carcinoma. These findings indicated a diagnosis of submandibular carcinoma T4aN2bM1 stage IVC. Pembrolizumab monotherapy was started, and tumor shrinkage was observed after three courses of treatment. At 1 year, complete response was achieved without adverse events, and treatment is ongoing. Despite a lack of evidence for the efficacy of immune checkpoint inhibitors in salivary gland carcinoma, the present case suggests that some patients might respond to this treatment. Hence, clinical trials are warranted.

Clinical value of adjuvant therapy on the prognosis of ductal carcinoma of the major salivary gland: a large-scale cohort study.

PURPOSE: To explore the clinical characteristics, prognostic factors, and value of adjuvant therapy for major salivary duct carcinoma (SDC). METHODS: Data of SDC patients who received surgery was obtained from Surveillance, Epidemiology, and End Results (SEER) database (2004-2016). Kaplan-Meier and Cox regression analyses were performed to assess prognostic factors. Propensity score matching (PSM) was done to evaluate the clinical value of adjuvant therapy. RESULTS: A total of 287 patients were enrolled. The 5-year overall survival (OS) and disease-specific survival (DSS) rates were 53.8% and 70.8%, respectively. In the univariate analysis, tumor size, T, N, TNM staging, SEER combined staging, number of regional lymph nodes examined, and number of positive lymph nodes were associated with OS and DSS. Age and primary surgical methods were also related to OS. Among patients with negative lymph nodes, patients with tumor size > 4 cm had significantly worse prognosis (P = 0.009). Multivariate analysis showed that age > 75 years, T3-4, and positive lymph nodes were independent risk factors for SDC. After PSM, the prognostic factors were age, tumor site, and T and N stage. Postoperative radiotherapy could improve OS in patients with tumor size > 4 cm (P = 0.049). CONCLUSIONS: Advanced age, submandibular gland lesions, T3-4 stage, and lymph node involvement were independent prognostic factors for SDC. In patients with tumors > 4 cm, adjuvant radiotherapy improved the OS of SDC patients.

Invasive and Non-invasive Ductal Carcinoma within Malignant Phyllodes Tumour with Axillary Lymph Node Metastases.

Phyllodes tumours are uncommon breast neoplasms constituting 1-2% of breast malignancies. Metastasis is usually haematogenous, and axillary lymph node dissection is not routinely performed. A phyllodes tumour with concomitant invasive ductal carcinoma (IDC) is even rarer. When IDCor ductal carcinoma in-situ (DCIS) is detected, the management of the condition changes completely. We report a case of a 22-year female presenting with a mass in the right breast and palpable axillary lymph nodes. The pathological examination demonstrated a malignant phyllodes tumour with concomitant IDC and DCIS. The patient elected to have modified radical mastectomy, and the pathological examination showed metastasis in the axillary lymph nodes. The patient was administered appropriate therapy. At the last visit, she did not have the clinical signs of disease. This is the first youngest case of axillary lymph node metastases with both DCIS and IDC on pathological examination in malignant phyllodes tumour. Key Words: Malignant phyllodes, Invasive ductal carcinoma, Ductal carcinoma in-situ, Lymph node metastasis.

Does the number of cell forming tumor budding alter the prognostic value in invasive ductal carcinoma of breast?

BACKGROUND AND OBJECTIVE: The most commonly used definition for tumor budding (TB) is a single or a cell cluster of tumor cells up to 4 cells. However, there are different opinions regarding the number of cell (NOC) forming TB. It has been proven that TB is associated with poor prognostic factors in most tumors. The current study, it was aimed to investigate the prognostic value of NOC forming TB in invasive ductal carcinoma of the breast. MATERIALS AND METHODS: 326 cases with the diagnosis of invasive ductal carcinoma were examined. The NOC forming TB was counted from hematoxylin and eosin stained slide under X200 magnification for each case, and scoring five different TB as 1, ≤ 2, ≤ 3, ≤ 4, ≤ 5, respectively. Receiver operating characteristic (ROC) analysis based on survival was performed for each TB value separately, and the cut-off was determined. RESULTS: All TB values were associated with poor outcome (p < 0.001), presence of distant metastasis (p < 0.001), high Ki67 proliferation index (p < 0.05), advanced stage (p < 0.05), presence of lymphovascular invasion (p < 0.001), and metastatic axillary lymph node (p < 0.001). According to ROC analysis performed to compare the predictiveness of survival, the area under the curve was similar for all TB values. CONCLUSION: TB was associated with poor prognostic parameters, and the prognostic value of TB was not affected by NOC forming TB. The NOC up to 4 cells which have been accepted for colon carcinomas, could also provide practicality in breast carcinomas.

WHO Classification of Tumours fifth edition: evolving issues in the classification, diagnosis, and prognostication of prostate cancer.

The fifth edition of the WHO Classification of Tumours of the Urinary and Male Genital Systems encompasses several updates to the classification and diagnosis of prostatic carcinoma as well as incorporating advancements in the assessment of its prognosis, including recent grading modifications. Some of the salient aspects include: (1) recognition that prostatic intraepithelial neoplasia (PIN)-like carcinoma is not synonymous with a pattern of ductal carcinoma, but better classified as a subtype of acinar adenocarcinoma; (2) a specific section on treatment-related neuroendocrine prostatic carcinoma in view of the tight correlation between androgen deprivation therapy and the development of prostatic carcinoma with neuroendocrine morphology, and the emerging data on lineage plasticity; (3) a terminology change of basal cell carcinoma to "adenoid cystic (basal cell) cell carcinoma" given the presence of an underlying MYB::NFIB gene fusion in many cases; (4) discussion of the current issues in the grading of acinar adenocarcinoma and the prognostic significance of cribriform growth patterns; and (5) more detailed coverage of intraductal carcinoma of prostate (IDC-P) reflecting our increased knowledge of this entity, while recommending the descriptive term atypical intraductal proliferation (AIP) for lesions falling short of IDC-P but containing more atypia than typically seen in high-grade prostatic intraepithelial neoplasia (HGPIN). Lesions previously regarded as cribriform patterns of HGPIN are now included in the AIP category. This review discusses these developments, summarising the existing literature, as well as the emerging morphological and molecular data that underpins the classification and prognostication of prostatic carcinoma.

Squamoid Eccrine Ductal Carcinoma of the Eyelid: Clinicopathologic Correlation of a Case.

Squamoid eccrine ductal carcinoma (SEDC) is a rare cutaneous neoplasm that often manifests as a plaque or nodule in sun-exposed areas of older patients. Herein, the authors report the first case of SEDC in the eyelid. A 76-year-old man presented with a 2.5 × 1.5 mm area of left upper eyelid erythema, thickening, ulceration, and scaling with madarosis superotemporally just above the lash line. Full-thickness wedge biopsy demonstrated irregular epithelial tubules with nuclear atypia and focal squamous differentiation, consistent with SEDC. The patient underwent Mohs resection and has had no recurrence approximately 27 months after surgical removal. The authors present this case to raise awareness of SEDC to ophthalmologists as all previous cases have been described in the nonophthalmic literature. A full-thickness biopsy is recommended to avoid misdiagnosing SEDC as squamous cell carcinoma (SCC), a less aggressive tumor. With greater awareness, there may be increased recognition of this likely underreported, more malignant entity.