Compiled by: Wei Jianguo, Wang QiangMolecular alterations may confirm the classification of certain diseases
This mainly refers to the fact that although papillary sialaloma (SP) is still a benign tumor and different from other papillary tumors, there is a new understanding of this disease. SP, inversion ductal papilloma and intraductal papilloma belong to the same category of ductal papilloma, which is a group of rare diseases that occur in the large excretory duct of the salivary gland, mainly in the small salivary gland; The key features are detailed in Table 1.
Table 1Comparison of salivary ductal papilloma characteristics.
SP resembles a papillary syringocystadenoma. Patients are generally 50 to 60 years old, but the age distribution is broad, with a slight increase in males. Clinically, it usually presents as a papillary lesion of the oral cavity rather than a submucosal mass. Histologically, the surface of the SP is an exophytic squamous component, with an endophytic component at the base with an unequal number of papillary eosinophilic ductal epithelial hyperplasia and a surrounding basal lamina; There may also be mucus cells.
Figure 3Papillary sialadenoma. (a) Squamous papillary hyperplasia on the surface, (b) Tubular papillary eosinophilic ductal component at the base with a basal layer at the periphery.
Although the literature suggests that all types of ductal papillomas are rare**, the ** rate of SP is relatively high at 6-15%; There are also rare reports of malignant transformation. The morphology and mutational status of SP suggest that some intraductal carcinomas are involved. In fact, most of the currently known SPs have BRAF PThe V600E mutation, which also supports its classification as a benign tumor, is considered by both the fourth and fifth editions of the WHO as distinct from other types of ductal papilloma.
Figure 4Inverted papillomas, in which a nest of cells consisting of non-keratinizing cells or transitional epithelium grows inverted, with ductal epithelium around it, and generally resembles sinus inverted papilloma.
Molecular alterations may help identify new diseases
Microsecretory adenocarcinoma is a new disease included in the fifth edition of the WHO classification. This is a rare tumor that has recently been recognized, and is generally low-grade malignant; The tumor is more common in small salivary glands, and patients are 30-50 years old, with slightly more women.
Microsecretory adenocarcinoma is usually well defined, but there is mild invasion under the microscope. The morphology is cord-like and tubular microcysts with mucus in it, with a myxoid interstitium against the background. The microcapsule cavity is lined with a monolayer, dwarf cubic cell, with sparse cytoplasm and a single-form oval nucleus. Areas of cribriform growth may also be present, but some cases with this feature may actually be another newer species, microcribriform adenocarcinoma.
Microsecretory adenocarcinoma is generally a "transitional" intercalary phenotype; In other words, tumors in this group mostly express SOX-10 and S100 but not classical myoepithelial markers. However, as with many other tumors, microsecretory adenocarcinoma has inconsistent expression of p40 and p63.
Figure 5Microsecretory adenocarcinoma. (a) The tumor was cord-shaped, tubular and microcystic with mucus, and the cyst cavity was lined with cubic cells with a single morphology, with sparse cytoplasm and an oval nucleus with a mucinoid interstitium background; Immunohistochemistry expressed SOX-10(b), positive for p63, but negative for p40.
Microsecretory adenocarcinoma has a MEF2C::SS18 fusion, which has actually reaffirmed that this is a new tumor species. This fusion can be detected by FISH and other methods (e.g., NGS); In contrast, microcribbular adenocarcinoma of the related disease mentioned above is characterized by SS18::ZBTB7A fusion.
One of the differential diagnoses of microsecretory adenocarcinoma is mainly secretory carcinoma. Both tumor types have intraluminal mucus, and microsecretory adenocarcinoma is also more common with extracellular mucinoid interstitium. The tubular microcystic structure in microsecretory adenocarcinoma is more homogeneous, lined with monolamana cells, and the cytoplasm is generally scarce. Secretory carcinoma, on the other hand, has a richer cytoplasmic morphology, is inconsistent, and has vacuolar shapes. In terms of immunohistochemistry, mammaglobin was negative for microsecretory adenocarcinoma and positive for secretory carcinoma.
There are also rare subtypes of microsecretory adenocarcinoma that can have spindle cell metaplasia. It is thought that microsecretory adenocarcinoma can also undergo high-grade transformation, that is, it manifests as solid overgrowth and the appearance of classic aggressive markers, such as pleomorphism and nuclear **. The overall prognosis of microsecretory adenocarcinoma is good, but it can be locally invasive in the case of high-grade transformation, and one case of microsecretory adenocarcinoma with distant metastasis has been reported in the literature.
Figure 6In microsecretory adenocarcinoma, spindle cell changes were rare, and the inset showed that the SS18 break probe was detected by FISH, and the results were positive. In terms of ultrastructure, the diseased cells are secretory, with significant microvilli, Golgi apparatus and intracytoplasmic vacuoles.
To be continued
Previous Review: Molecular Epochology Pathology: A Case Study of Salivary Tumors (1).