Secretory carcinoma (SC) is a recently described entity occurring in the salivary glands. Before its description, SC was frequently classified as acinic cell carcinoma (ACC) or adenocarcinoma, not otherwise specified. Its particular histopathological and immunohistochemical characteristics are reminiscent of breast secretory carcinoma. Moreover, it displays a characteristic t(12;15) (p13;q25) translocation that results in the
A 27-year-old Hispanic male patient with no relevant clinical history presented with a mass in the right parotid region, adjacent to the angle of the mandible. According to the patient, the mass had slowly but progressively increased in size over a period of 18 months, measuring approximately 1.5 centimeters in its greatest dimension. On physical examination, the mass was painless, firm in consistency, and nonmovable and displayed no changes in the overlying skin. No other masses were found in the face or neck and there was no evidence of facial nerve paralysis. The patient reported no other symptoms, such as xerostomia and sialorrhea.
An incisional biopsy was performed as a first approach to study the lesion. Macroscopic analysis of the biopsy sample was limited because the tissue was fragmented. Microscopic examination revealed an epithelial neoplasm with a lobular growth pattern, dense fibrous connective septa, and solid microcystic areas and tubular structures (Figures
SC of parotid gland, epithelial neoplasm with a lobular growth pattern, and solid microcystic areas (a-b) [H/E 10X and 40X]. Tubular structures showing abundant, foamy, PAS- and Alcian Blue-positive intraluminal material (c-d). The tumor cells positive for S100 and mammaglobin (e-f), but negative for DOG-1 (g).
MASC of parotid gland, epithelial neoplasm with a lobular growth pattern, and solid microcystic areas [H/E 10X]
MASC of parotid gland, epithelial neoplasm with a lobular growth pattern, and solid microcystic areas [H/E 40X]
Tubular structures showing abundant, foamy, PAS-positive intraluminal material [
Tubular structures showing abundant, foamy, Alcian Blue-positive intraluminal material [
The tumor cells positive for S100 [
The tumor cells positive for mammaglobin [
The tumor cells negative for DOG-1 [
The advised surgery was not performed soon after the diagnosis, but only six weeks later. Within that period, a local recurrence developed from the original lesion in the same area where the biopsy had been taken. This mass was found during the preoperative check-up. It was painless, firm, and measured 0.5 cm in diameter. Finally, a superficial parotidectomy and a supraomohyoid neck dissection were performed as a definitive treatment. No lymph node showed evidence of tumor cells, and surgical margins were negative. After three days of uneventful postoperative recovery, the patient was discharged from the hospital.
Skálová et al. first described SC in 2010 with the name of mammary analogue secretory carcinoma (MASC) [
SC shares the histological, immunohistochemical, and genetic characteristics of breast secretory carcinoma, an extremely rare neoplasm that usually affects young patients and generally has an indolent clinical course [
SC appears mostly in adults with a mean age of 47 years at diagnosis. As opposed to acinic cell carcinoma, SC has a slightly higher prevalence in men than in women [
Clinically, SC presents as a slowly but progressively growing firm mass that is, as in our case, usually painless or nearly painless (see Table
Clinicopathological characteristics of secretory carcinoma.
|
47 years |
|
|
|
Equal distribution or a slight male predominance (1.5:1), depending on the series |
|
|
|
Parotid glands, without lateral predominance |
|
|
|
Progressively growing painless mass |
|
|
|
A firm mass with a rubbery consistency to the touch |
|
|
|
Eosinophilic cell proliferation forming lobules separated by thin fibrous septa and showing microcystic, tubular, papillary, or solid patterns and abundant PAS- and mucicarmine-positive secretion |
|
|
|
S-100 protein, mammaglobin, and vimentin positive |
|
|
|
Characteristic t(12;15) (p13;q25) translocation with |
Histopathologically, SC presents as a well-defined cell proliferation with thin fibrous septa that may or may not show hyalinization and which give the lesion a lobular appearance. The growth pattern is eminently secretory and can be microcystic, tubular, solid, macrocystic, or papillary. A papillary-cystic pattern is common in SC cases, while a solid pattern is predominant in acinic cell carcinomas [
The immunohistochemical profile of SC consistently shows positivity, usually intense and diffuse, for mammaglobin, S-100 protein, and vimentin [
No single immunohistochemical marker makes the SC diagnosis possible. Several studies have shown that mammaglobin is highly sensitive but lacks sufficient specificity to be an individual diagnostic marker [
The characteristic molecular alteration of SC is the t(12;15) (p13;q25) translocation. This translocation causes the fusion of genes
For diagnosis, the three main characteristics of the original SC description should be considered. First, a histopathological pattern shows morphology suggestive of apocrine secretory epithelium, papillary-cystic or microcystic pattern, abundant PAS-positive eosinophilic secretion, and absence of basophilic zymogen granules in the tumor cell cytoplasm, the latter being a key difference from acinic cell carcinoma. Second, the immunohistochemical profile should include at least mammaglobin, S100 protein, and DOG-1 to guide the diagnosis. Finally, the presence of the t(12;15)
In typical cases such as ours, the histopathological study and the immunohistochemical profile are sufficient for diagnosis and do not require molecular confirmation [
Differential diagnosis of SC includes acinic cell carcinoma, intraductal carcinoma (low-grade cribriform cystadenocarcinoma), and low-grade mucoepidermoid carcinoma. Acinic cell carcinoma is the most important of these differentials (see Table
Key elements in the differential diagnosis of secretory carcinoma.
|
|
|
|
|
---|---|---|---|---|
|
Parotid gland (75%); present in minor salivary glands, more frequently than ACC, and in the oral cavity | Parotid (90%); very rarely in minor salivary glands | Parotid, most frequently; tongue (posterior region) and minor salivary glands | Parotid (50%) and oral cavity (palate and oral mucosa); very rarely (1-2%) in the submandibular gland |
|
||||
|
Slight male predominance | Female predominance | The same for both sexes | The same for both sexes |
|
||||
|
Predominantly tubular, microcystic, and solid |
Common: solid, follicular, and microcystic |
Encapsulated and cystic, with cribriform and papillary patterns | Heterogeneous pattern: solid and cystic with hydropic degeneration and metaplastic changes |
|
||||
|
Epithelial, without acinar differentiation | Acinar and basophilic | Monotonous, with ductal, cuboidal, and apocrine characteristics | Morphologically bland epidermoid, mucinous, and intermediate cells that are oncocytic, clear, or columnar/polygonal |
|
||||
|
Eosinophilic, granular, or vacuolated; no zymogen granules | PAS positive zymogen granules |
Eosinophilic, very infrequently with iron pigment | Abundant, clear (mucicarmine, Alcian blue, and PAS-diastase positive), eosinophilic, and foamy |
|
||||
|
Round or oval | Monomorphic | Clear vesicular nuclei with the appearance of frosted glass that overlap one another | Small hyperchromatic nuclei |
|
||||
|
S-100 protein and mammaglobin positive |
Mammaglobin and p63 negative |
S-100 protein, vimentin, and mammaglobin positive; p63- and calponin-positive myoepithelial cells | Positive p63 staining in epidermoid foci and usually S100 and mammaglobin negative |
|
||||
|
t(12;15) |
|
|
t(11;19) |
In general, the clinical course of SC is indolent. The risk of local recurrence and lymph node metastasis is 15% and 20%, respectively. The risk of distant metastasis is around 5% and cases with high-grade transformation have a worse prognosis [
Treatment of SC depends on the stage of the disease at diagnosis and on the tumor’s histological and molecular characteristics. The treatment of choice for low-grade SC is complete surgical resection. In this scenario, few cases show recurrence. In our case, however, the patient presented recurrence six weeks after initial biopsy, probably due to the presence of residual tumor cells. After the second surgery, no other recurrences were detected during the patient’s four-year follow-up.
Locoregional radiation therapy may be considered for large tumors or those that have shown perineural invasion or positive margins. The need for lymph node dissection depends on each case. In cases of SC with high-grade transformation, total resection of the affected gland and adjuvant radiotherapy is recommended. In addition, this type of neoplasm shows a greater propensity to metastasize to the cervical lymph nodes, which would suggest the need for lymph node dissection for optimal management of these patients [
Since not all pathology laboratories have the resources to perform the molecular analysis, histological study and immunohistochemistry are key tools for establishing the diagnosis when the clinical presentation, morphology, and immunohistochemical profile of the case typically conform to the SC description, as in our case. Even when a rare case is involved, it is important to keep in mind the typical findings and presentation, since it is probable that a larger number of clinicians will see these cases and thus potentially improve clinical practice. Our case report aims to demonstrate the importance of recognizing the typical presentation of a rare tumor so that a correct diagnosis can be made independently of molecular analysis.
The authors declare that there are no conflicts of interest regarding the publication of this paper.