An in-depth look at the clinical presentation of this rare tumor type.
Signet ring type cutaneous squamous cell carcinoma (cSCC) is an extremely rare variant, with fewer than 20 reported cases within the Medline database.1,2 Here, we present a case of signet ring cSCC and briefly summarize previously published reports.
An 87-year-old male presented with a cystic papule overlying the left zygomatic arch measuring 1.1 x 1.3 cm. A shave biopsy showed granulomatous inflammation suggestive of a ruptured cyst, but due to the superficial nature of the biopsy, no definitive pathology was identified. After six weeks, the biopsy site remained unhealed. A subsequent punch biopsy revealed an infiltrative carcinoma with focal epidermal connection composed of epithelioid-appearing cells with a clearing that gave them a signet ring-like appearance (Figure 1). Immunohistochemical (IHC) staining was positive for cytokeratin (CK) AE1/AE3 and negative for Mart 1, suggesting a diagnosis of signet ring cSCC.
Figure 1. Cells of interest with a central clearing displacing the nucleus towards the periphery (signet ring appearance).
On subsequent clinical examination, no palpable lymphadenopathy was appreciated, and a computed tomography scan of the neck revealed no abnormalities. Multidisciplinary evaluation recommended wide local excision (WLE) with margins of 1 cm and parotid sentinel lymph node biopsy (SLNB). Microscopically, the tumor showed invasive poorly differentiated SCC with focal signet ring-like morphology (Figure 2). There was no evidence of lymphovascular or perineural invasion. An incidental basal cell carcinoma was also identified alongside the previously noted cSCC (Figure 3). IHC analysis of the signet ring cell population revealed positivity for p40 and EMA, and negativity for SOX10 and mucicarmine (Figure 4), confirming a diagnosis of signet ring cSCC. Results of the SLNB were benign. Following 2 years of follow-up, the patient remains without signs of tumor recurrence.
Figure 2. Poorly-differentiated SCC displaying focal acantholysis and signet ring morphology.
Figure 3. Incidental BCC alongside cSCC. Given the tumor-free zone, we considered this an incidental case rather than a BCC/SCC collision or combined tumor.
Figure 4. Negative mucicarmine stain helps exclude the presence of mucin-producing cells.
Cutaneous squamous cell carcinoma is the second commonest skin cancer and has a median age at diagnosis of 77 years.1,3 While the majority of cSCC cases are successfully treated without further complications, approximately 1% to 5% of patients with cSCC will develop locoregional or distant disease.4,5
Certain high-risk features (such as deep invasion >2 mm, high-grade or desmoplastic tumors, or tumors exhibiting perineural or lymphovascular invasion) are associated with aggressive behavior and a less favorable prognosis.3 The signet ring morphology of cSCC is often regarded as aggressive, but this is largely limited to case reports and extrapolations from cases of poorly differentiated signet ring adenocarcinomas of the gastrointestinal tract.2
Classically, the signet ring morphology is associated with gastrointestinal adenocarcinoma, where intracellular mucin displaces the nucleus to the periphery, resulting in the distinctive signet ring appearance. However, in cases of cSCC lacking in mucin production, the mechanism behind this morphology remains elusive.2
As of May 2023, only 15 cases of signet ring cSCC have been reported within the Medline database (summarized in Table 1).2 We found that the median age of diagnosis of signet ring cSCC (78.5 years) was similar to that of cSCC overall (77 years).1,3 The head and neck were the most common locations. Only one case presented with lymph nodal involvement, and another reported a combined basal cell-signet-ring squamous differentiation. Treatments consisted of wide local excision and Mohs micrographic surgery (MMS). Follow-up data were accessible for three cases: a 1.5-cm tumor located on the left lateral canthus of a 67-year-old male treated with MMS (follow-up: 13 months); a 3.1-cm tumor located on the 4th digit of an 83-year-old male treated with excision (follow-up: 36 months); and a 5.6-cm tumor in the parotid region of a 66-year-old male-to-female transgender patient treated with WLE (follow-up: six months). All three patients were reported to be alive and free of disease at the time of their respective publications.
Immunohistochemical staining is essential in diagnosing signet ring cSCC. In our case, negativity for mucicarmine excluded adenomatous or adenosquamous origin (Figure 4), while positivity for p40 and CK AE1/AE3 confirmed a diagnosis of cSCC.
This report contributes an additional case to the limited body of existing literature on signet ring cSCC and underscores the variable clinical presentation of this rare tumor. Initially resembling an epidermoid cyst, our case emphasizes the importance of maintaining a high index of suspicion when evaluating non-healing wounds on the head and neck of elderly patients. Through close follow-up, low threshold for additional biopsy, and interdisciplinary collaboration, our patient has remained recurrence-free for two years.
The authors report no relevant financial disclosures.
1. Venables ZC, Autier P, Nijsten T, Wong KF, et al. Nationwide incidence of metastatic cutaneous squamous cell carcinoma in England. JAMA Dermatol. 2019 Mar 1;155(3):298–306.
2. Satala CB, Kovacs Z, Bara T Jr, Jung I, et al. Signet-ring cell squamous cell carcinoma: A biphenotypic neoplasm of the gastro-esophageal junction with uncertain biological Potential: Case Report and Literature Review. Int J Mol Sci. 2023;24(11):9535.
3. Ciążyńska M, Kamińska-Winciorek G, Lange D, Lewandowski B, et al. The incidence and clinical analysis of non-melanoma skin cancer. Sci Rep. 2021 Feb 22;11(1):4337.
4. Stefanovic N, Fitzmaurice CJ, Ormond P, Irvine AD, et al. Risk factors for distant metastasis in cutaneous squamous cell carcinoma. Br J Dermatol. 2022 Sep;187(3):435–6.
An in-depth look at the clinical presentation of this rare tumor type.