By this time of surgery, the tumor had significantly increased in size to clinically measure 4.7 x 2.3 cm. First layer histology revealed an aggressive, well-differentiated SCC extending deep into fat with perineural involvement. A second layer was taken; given the extensive involvement of the deep tissue, it was decided to stop MMS, consult head and neck surgical oncology, and leave the current surgical defect open, which measured almost 6 cm.
Upon workup, computed tomography (CT) of the head and neck revealed no underlying bony defects or evidence of regional metastatic disease, and although the CT of the chest demonstrated granulomatous disease, there was no evidence of metastatic disease either. Head and neck surgical oncology had a long discussion with the patient and his wife regarding further management of the SCC – watchful waiting, re-excision under general anesthesia with cardiology clearance, or radiotherapy. Given his age, comorbidities, and further risks associated with continued treatment, the patient opted for closure of the surgical site with a delayed skin graft and watchful waiting.
Three months after MMS, the patient presented to his primary care doctor with a well-healed graft site over the left cheek. No local recurrence of the SCC was noted at this time. The patient did not demonstrate evidence of metastatic disease to regional lymph nodes.
Upon workup, computed tomography (CT) of the head and neck revealed no underlying bony defects or evidence of regional metastatic disease, and although the CT of the chest demonstrated granulomatous disease, there was no evidence of metastatic disease either. Head and neck surgical oncology had a long discussion with the patient and his wife regarding further management of the SCC – watchful waiting, re-excision under general anesthesia with cardiology clearance, or radiotherapy. Given his age, comorbidities, and further risks associated with continued treatment, the patient opted for closure of the surgical site with a delayed skin graft and watchful waiting.
Three months after MMS, the patient presented to his primary care doctor with a well-healed graft site over the left cheek. No local recurrence of the SCC was noted at this time. The patient did not demonstrate evidence of metastatic disease to regional lymph nodes.
DISCUSSION
SCCs arise secondary to clonal expansion of keratinocytes harboring ultraviolet-induced DNA mutations, specifically the TP53 gene. Further “hits†to keratinocyte DNA affect genes important for cell proliferation, adhesion, and migration causing locally invasive (perineural and/or perivascular), as well as possible metastatic disease. SCCis is an early, superficial carcinoma that can be treated using a multitude of techniques including liquid nitrogen, topical chemotherapeutics, curettage with or without electrodessication, photodynamic therapy, local radiation, laser therapy, and excision. However, with invasion, therapeutic options become limited – depending on the anatomic location, medical practitioners will often favor surgical techniques including wide local excision or Mohs micrographic surgery.2
Progression from SCCis to invasive SCC is relatively rare, with a reported 3%–5% conversion rate.2 Mutations in key oncogenes or tumor suppressor genes may have resulted in the rapid progression of our tumor. Future advancements in whole genome sequencing may allow for characterization of the initial SCCis lesion versus the subsequent SCC to reveal specific DNA mutations associated with an increased risk of invasion and perineural involvement. Given recent developments in molecular characterization of melanomas in the outpatient setting, it is possible that sequencing of NMSCs is right around the corner. It is also possible that sampling bias during the initial biopsy may have contributed to misdiagnosis.4
As authors, we feel that this case is important to present to the dermatologic community, as it embodies the therapeutic and diagnostic challenges dermatologic surgeons encounter when faced with an aggressive, invasive carcinoma. Given our tumor’s size on presentation for MMS, perineural extension and patient comorbities, this aggressive SCC proved a therapeutic challenge requiring a multidisciplinary approach with input from ENT, head and neck surgical oncology, and radiology. Although ultimately it was decided to discontinue further treatment and close the surgical defect with a graft, in other cases where patients are younger or have less comorbid disease, additional therapy with surgery and/or radiation may be warranted for locally invasive SCC.
Progression from SCCis to invasive SCC is relatively rare, with a reported 3%–5% conversion rate.2 Mutations in key oncogenes or tumor suppressor genes may have resulted in the rapid progression of our tumor. Future advancements in whole genome sequencing may allow for characterization of the initial SCCis lesion versus the subsequent SCC to reveal specific DNA mutations associated with an increased risk of invasion and perineural involvement. Given recent developments in molecular characterization of melanomas in the outpatient setting, it is possible that sequencing of NMSCs is right around the corner. It is also possible that sampling bias during the initial biopsy may have contributed to misdiagnosis.4
As authors, we feel that this case is important to present to the dermatologic community, as it embodies the therapeutic and diagnostic challenges dermatologic surgeons encounter when faced with an aggressive, invasive carcinoma. Given our tumor’s size on presentation for MMS, perineural extension and patient comorbities, this aggressive SCC proved a therapeutic challenge requiring a multidisciplinary approach with input from ENT, head and neck surgical oncology, and radiology. Although ultimately it was decided to discontinue further treatment and close the surgical defect with a graft, in other cases where patients are younger or have less comorbid disease, additional therapy with surgery and/or radiation may be warranted for locally invasive SCC.
DISCLOSURES
The authors received no funding for this research.
The authors have no relevant conflicts of interest to disclose.
REFERENCES
1. Fernandez-Figueras, MT, Carrato, C, Saenz, X, et al. Actinic keratosis with atypical basal cells (AKI) is the most common lesion associated with invasive squamous cell carcinoma of the skin. J Eur Acad Dermatol Venereol. 2015 May;29(5):991-7.
2. Neubert, T, Lehmann, P. Bowen’s disease – a review of newer treatment options. Ther Clin Risk Manag. 2008 Oct;4(5):1085-95.
3. Newsom, E, Connolly, K, Phillips, W, et al. Squamous cell carcinoma in situ with occult invasion: a tertiary care institutional experience. Dermatol Surg. 2019 Nov;45(11):1345-52.
4. Chuang, GS, Lu, LK, Cummins, DL, et al. Incidence of invasive squamous cell carcinomas in biopsy-proven squamous cell carcinomas in situ sent for Mohs micrographic surgery. Dermatol Surg. 2012 Sep;38(9):1456-60.
2. Neubert, T, Lehmann, P. Bowen’s disease – a review of newer treatment options. Ther Clin Risk Manag. 2008 Oct;4(5):1085-95.
3. Newsom, E, Connolly, K, Phillips, W, et al. Squamous cell carcinoma in situ with occult invasion: a tertiary care institutional experience. Dermatol Surg. 2019 Nov;45(11):1345-52.
4. Chuang, GS, Lu, LK, Cummins, DL, et al. Incidence of invasive squamous cell carcinomas in biopsy-proven squamous cell carcinomas in situ sent for Mohs micrographic surgery. Dermatol Surg. 2012 Sep;38(9):1456-60.
AUTHOR CORRESPONDENCE
Margit Juhasz MD jmjuhasz@uci.edu
