- Here is a case of an around 49-year-old male patient who presented with sudden onset of headache and syncope. At present CT scan of the brain shows some around 3x2x1.5 size mass lesion in temporoparietal region of the brain. Biopsy bits are received for evaluation.
- The patient had a history of salivary duct adenocarcinoma of parotid gland, which was adequately treated 3 and a half years ago, in form of total parotidectomy and radical neck dissection. The histology analysis revealed salivary duct adenocarcinoma with free surgical margins and metastatic disease in 6 neck nodes. Immunohistochemical staining on the original parotid gland tumor showed positivity for CK7 and E-cadherin. Weak focal positivity was also observed for CEA and AMACR. Tumor cells were negative for CK5/6, p63, S100 and c-erbB-2.
- Microscopic examination of brain biopsy bits reveals a tiny area of unremarkable glial tissue with a sharply demarcated cribriform architecture of the tumor. Predominant architecture is of cribriform along with areas of ductal/glandular patterns.
- Neoplastic epithelial cells show large pleomorphic vesicular nuclei, some with distinct and prominent nucleoli and abundant pink cytoplasm. Few cells show severe pleomorphism and atypical mitotic features.
Practical Points of Pathoclinics:
- Salivary duct carcinoma (SDC) is an uncommon salivary gland tumor, frequently affecting the parotid gland. It also affects the submandibular glands and minor salivary glands. It may arise de novo or from malignant transformation of previous pleomorphic adenoma.
- It has a poor prognosis due to rapid growth, frequent recurrence, regional nodal and distant metastasis. SDC has a high metastatic potential via the hematogenous and lymphatic pathways. Common distant metastatic locations are the lung and bone. Liver, skin and brain are also the sites of metastasis but with a relative lower frequency.
- Is the distinction between salivary duct carcinoma (high-grade) and low-grade intraductal/cribriform salivary duct carcinoma important? The answer is YES. There is a significant morphologic overlap between low-grade intraductal/cribriform salivary duct carcinoma and high-grade salivary duct carcinoma. However, there is no or very little relationship between these two.
- Low-grade intraductal salivary duct carcinoma is characterized by an intraductal/in situ growth pattern with low-grade/bland cytologic features and favorable outcomes. Morphologically, multiple variable size cysts, solid nests, papillary, micropapillary and cribriform architecture with Roman Bridges, epithelial tufts and fibrovascular cores are reminiscent of low-grade mammary ductal carcinoma in situ. In low-grade, tumor cells are small to medium in size with round to oval nuclei, finely dispersed chromatin and pale eosinophilic cytoplasm. It is necessary to look for high-grade cytology and invasive carcinoma through adequate gross sectioning. Tumor cells are positive for keratins, SOX10 and S100 protein, while surrounded myoepithelial cells are positive for p63. In contrast to high-grade salivary duct carcinoma, low-grade intraductal/cribriform salivary duct carcinoma is negative for AR. Only occasional RET rearrangement is found in low-grade intraductal/cribriform salivary duct carcinoma at the molecular level. The acceptable terminology for low-grade salivary duct carcinoma and cribriform cystadenocarcinoma is low-grade intraductal carcinoma of the salivary gland.
- Salivary duct carcinoma (High-grade) is characterized by large round to oval nuclei with conspicuous nucleoli and abundant eosinophilic cytoplasm, in a glandular/ductal, solid sheet, cords, nests and cribriform pattern. Comedo necrosis is common, especially in in situ areas. Such morphology resembles that of high-grade duct carcinoma of breast, including variant pattern like papillary, cribriform, and comedo-type pattern. Minor morphological variations are mucin-rich foci, sarcomatoid and invasive micropapillary pattern, oncocytic, and rhabdoid cell cytology, can be seen in high-grade tumors. On immunohistochemistry, most cases are positive for androgen receptor (AR) (strong and diffuse), GCDFP-15, CK7 and GATA3. Positivity of CK7 and GATA3 are only partially helpful to clinch the diagnosis of metastatic malignancy of salivary gland origin as CK7 and GATA3 also come positive in breast carcinomas while CK7 in lung carcinomas. HER2 and PSA can be positive in up to half of cases. Tumor cells are negative for ER, PR (rule out breast carcinoma), DOG1 (rule out adenoid cystic carcinoma), p63, p40 (rule out high-grade muco-epidermoid carcinoma), TTF-1, Napsin (rule out adenocarcinoma of lung), NKX3.1 (rule out prostatic adenocarcinoma), S-100, SOX10 (rule out low-grade intraductal/cribriform salivary duct carcinoma). AR negative cases should be closely evaluated to rule out other differentials. Weak focal AR expression can be seen in pleomorphic adenoma, adenoid cystic carcinoma, and acinic cell carcinoma. Expression or amplification of HER2 can be seen in mucoepidermoid carcinoma, adenoid cystic carcinoma, acinic cell carcinoma, and squamous cell carcinoma. Recent molecular analyses have revealed alterations in many common oncogenes and tumor suppressor genes, including TP53, HRAS, PIK3CA, PTEN, and BRAF, which raise the hope of molecularly targeted therapy. At present, the association between PD-L1 expression and prognosis has not been evaluated with firm evidence.
- Poor prognostic indicators of salivary duct carcinoma are:
- tumor size > 3 cm
- patient’s age over 50 years
- lymph node involvement
- high tumor grade
- ≥5 Poorly differentiated clusters (tumor cell clusters composed of more than 5 cells without gland formation)
- sarcomatoid, micropapillary, and rhabdoid morphology
- extracapsular spread
- perineural invasion
- lymphovascular invasion
- ≥30 Mitoses/10 high-power fields
- positive surgical margins
- distant metastases
- overexpression of HER2/neu
- p53 extreme negative/positive staining (null or diffuse strong expression)
- CK5/6 positive staining
- Negative AR (androgen receptor)
- Gross total resection with/without neck node resection followed by postoperative radiation is the recommended treatment, even in cases without nodal metastasis at the initial diagnosis. The presence of any poor prognostic indicators requires close follow-up with postoperative radiotherapy and chemotherapy. The role of chemotherapy is somewhat unclear, with limited benefit. The Latest NCCN guidelines recommend AR therapy and anti-HER2 therapy for AR-positive and HER2-overexpressing tumors, respectively. The 5-year survival rate for stage I disease was 42%, stage II was 40%, stage III was 30.8%, and stage IV was 23.2%.
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- Kantamani D, Bandaru SS, Miatech JL, Stagg MP. Salivary Duct Carcinoma: Case Reports and Brief Review of the Literature. Case Rep Oncol Med. 2021 Oct 11;2021:2672772. doi: 10.1155/2021/2672772. PMID: 34671494; PMCID: PMC8523288.