Abstract
Sclerosing polycystic adenosis (SPA) is a rare tumor of the major or minor salivary glands that is similar to tumors of the breast. SPA has been part of new entries of salivary gland tumor in the World Health Organization Classification since 2022. A 21-years-old female represented in our hospital with a nodule in the upper lip that was present for some months. A conservative surgical excision of the tumor was done and the lesion underwent a histopathologic examination. The immunohistochemical findings (Ki-67 <2%, focal S100, focal p16) supported a benign diagnosis. Histopathological examination describes a biphasic tumor with the presence of multiple cystic dilated ducts in a sclerotic stroma. Less than 100 reported cases have been in the literature.
Introduction
Sclerosing polycystic adenosis (SPA) is a recently described, rare, reactive/neoplastic, inflammatory process of the major or minor salivary glands that is similar to fibrocystic changes, sclerosing adenosis, and adenosis tumors of the breast [1].
SPA has been part of new entries of salivary gland tumor in the World Health Organization Classification since 2022 [1, 2].
Smith et al. were the first to report SPA cases in 1996 in a series of nine cases (2). They characterized the histological features as follows: fibrotic, cystic alterations, apocrine metaplasia, and proliferations of ducts and acini composed of the cells with abundant eosinophilic cytoplasmic granules, and myoepithelial cells in variable proportions [2].
The etiology is still unknown but Bishop and Thompson have noticed that all SPA lesions harbored genetic mutations in the phosphatidylinositol 3-kinase pathway [1]. SPA is rare, with fewer than 100 reported cases in the literature [3].
Therefore, we report a case of SPA of a minor gland in the upper lip, describing its microscopic features and its immunohistochemical profile to evaluate the nature of this lesion.
Case report
A 21-years-old female presented with swelling in the philtrum of the lip, which was created after trying to remove a sebaceous gland by squeezing it. The swelling persisted for at least 6 months.
Clinically the swelling was well circumscribed, solid, and not painful (Figs 1 and 2). Ulceration and tenderness were not evident during the examination. A conservative surgical excision of the tumor was done from an intraoral approach and the lesion underwent a histopathologic examination.
A firm painless nodule at the right side of the philtrum in the upper lip in frontal view.
A firm nodule at the right side of the philtrum in the upper lip; on lateral view, loss of the normal philtrum is evident.
Materials and methods
The specimen was fixed in 10% formalin, embedded in paraffin, and routinely stained with hematoxylin and eosin. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue sections using antibodies against p16, Ki-67, and S100. Antigen retrieval was performed by heat-induced epitope retrieval using citrate buffer, pH 6.0/ethylenediaminetetraacetic buffer, pH 9.0 at 95°C–98°C for 20 min.
Results
Histopathological examination described a biphasic tumor with the presence of multiple cystic dilated ducts in a sclerotic stroma. The ductal cells had eosinophilic cytoplasm (Figs 3 and 4). The tumor had free margins. No significant inflammatory infiltrate was observed.
Photomicrograph of the lesion demonstrating a biphasic population with cystic, dilated ducts, and acinar structures embedded in a densely sclerotic stroma (H&E, 100×).
High-power view showing ductal cells with abundant eosinophilic cytoplasm (arrow) and peripheral myoepithelial cells (H&E, 400×).
An immunohistochemical profile was required to understand better the nature of the lesion. More specifically, an examination of the S100, p16, and Ki67 markers was carried out.
p16 expression is observed in a subset of epithelial cells with a focal/patchy distribution. This staining pattern likely reflects alterations in cell-cycle regulatory pathways and does not demonstrate the diffuse “block-type” positivity typically associated with Human Papilloma Virus (HPV) -related lesions (Fig. 5).
P16 immunohistochemistry demonstrating focal and heterogeneous epithelial staining, without diffuse block-type positivity, a pattern not supportive of high-risk HPV-associated disease.
Immunohistochemical examination with Ki-67 revealed <2% positivity in lesional cells, indicating very low proliferative activity and confirming the benign nature (Fig. 6).
Ki-67 immunohistochemistry showing a very low proliferative index, with nuclear positivity in <2% of lesional cells.
S100 immunohistochemistry showed focal and heterogeneous staining of epithelial and myoepithelial cells within the cystically dilated ducts and acinar structures of SPA (Fig. 7). S100 positivity confirmed the biphasic nature of the lesion (epithelial and myoepithelial cells).
S100 immunohistochemistry showing focal staining of ductal epithelial and myoepithelial cells within the lesion (×100).
Epstein Barr Virus Encoded Small RNAs (EBER) in situ hybridization was not performed due to limited availability of the test. However, the morphological features and immunophenotypic profile was considered sufficient to establish the diagnosis of SPA.
The patient remained free of disease after 1-year of follow-up.
Discussion and conclusion
SPA is a rare condition primarily of the major salivary glands [4]. In minor glands, they are rarely found in buccal mucosa, floor of the mouth, and retromolar area. Our article and Puranik et al.’s are the only two documents that report the presence of the lesion in the minor salivary glands located in the lips. We present a case of an SPA lesion in the upper lip, meanwhile in Puranik et al.’s article, the lesion was present in the lower one [5]. Special and rare cases are also documented by authors such as Pfeiffer et al. [6] who reported a case of this type of tumor being present in the lacrimal gland. Braz-Silva et al. [7] reported a case of the lesion in the ventral surface of tongue and Su et al. [8] have reported a case of the presence of Polycystic Sclerosing Adenoma (PSA) in sinonasal tract. These reports, together with the present case, highlight the broad anatomical distribution of SPA and demonstrate that this lesion may develop in sites containing either major or minor salivary gland-type tissue. Our case therefore adds further evidence that SPA should be considered in the differential diagnosis of glandular lesions occurring at uncommon anatomical sites.
Table 1 presents a summary of the distribution of anatomic location, gender, and age in articles that have document cases of SPA.
Some reported cases of SPA
| Authors | Age | Gender | Anatomic location |
|---|---|---|---|
| Gnepp et al., 2006 [12] |
|
|
|
| Su et al., 2013 [8] |
|
|
|
| Noonan et al., 2007 [13] |
|
|
|
| Rathi et al., 2021 [4] |
|
|
|
| Pfeiffer et al., 2013 [6] |
|
|
|
| Puranik et al., 2018 [5] |
|
|
|
| Marques and Félix, 2014 [11] |
|
|
|
| Braz-Silva et al., 2018 [7] |
|
|
|
| Meer and Altini, 2008 [14] |
|
|
|
| Mokhtari et al. 2014 [15] |
|
|
|
| Skálová et al. 2002 [16] |
|
|
|
According to the review done by Rathi et al., SPA shows no gender predilection, even though this type of tumor histologically resembles a tumor found in women’s breasts. SPA occurs over a wide age spectrum of 7–84 years [4].
The etiology of SPA is still unknown. Skálová et al. demonstrated a clonal biology of SPA and concluded that SPA is a neoplasm and not just a reactive process, based on a 30% recurrence rate with hyperplastic, atypical, and dysplastic microscopic features [9]. Swelam documented three cases of SPA with the presence of Epstein Barr Virus (EBV) [10], and Marques and Félix have reported a case of carcinoma arising from SPA of the salivary gland [11]. In our case, there was no recurrence after 1 year of follow-up. The low Ki-67 proliferative index, together with the absence of morphological or immunohistochemical features suggestive of HPV-related changes, supports the benign nature of the lesion. Although EBER in situ hybridization was not performed to formally assess EBV infection, the overall morphology was typical of a benign process and showed no features suggestive of EBV-associated pathology.
Conflicts of interest
None declared.
Funding
None declared.
