Multiple cutaneous squamous cell carcinomas arising in a patient with generalized morphea

Association of cutaneous scleroderma and squamous cell carcinoma (SCC) has been reported in a few cases. We report a new case of multiple SCC which occurred in sclerotic patches on the leg. The role of factors explaining this association is discussed as immunosuppression or ulcerations.     

Multiple cutaneous squamous cell carcinomas in a patient with chronic lymphocytic leukemia

A 79-year-old white woman had stasis dermatitis and multiple cutaneous squamous cell carcinomas not only in the exposed areas of the face, neck, and arms, but also on the lower legs in the area of dermatitis. Further evaluation revealed early chronic lymphocytic leukemia. This case illustrates the need to search for an underlying abnormality in patients with multiple or unusual skin cancers and to examine biopsy specimens from suspicious skin lesions in immunocompromised patients.     

PGP 9.5 expression in cutaneous keratoacanthomas and squamous cell carcinomas

The aim of the study was to investigate the expression of PGP 9.5 in cutaneous keratoacanthomas (KAs) and squamous cell carcinomas (SCCs). Thirty-one cases of KA (10 in the growth stage, 9 in the mature phase and 12 in the involution stage) and 36 SCCs including 13 well differentiated cases, 12 moderately differentiated tumors, 7 poorly differentiated lesions and 4 pseudoadenoid entities were investigated. PGP 9.5 expression was positively correlated with tumor stage (P < 0.001) and potential perineural invasion (P < 0.001). There was no significant difference in the distribution of patients presenting variable levels of PGP 9.5 staining with regard to maximal tumor size and the extent and degree of stromal invasion. PGP 9.5 expression proved closely associated with tumor aggressiveness and is classified as a marker for predicting the outcome of resection-treated skin cancer patients.     

Analysis of the vitamin D system in cutaneous squamous cell carcinomas

BACKGROUND: Increasing evidence points at an important function of vitamin D metabolites for growth regulation in various tissues, and new vitamin D analogs are interesting candidates for the treatment of malignancies, including squamous cell carcinomas (SCC). METHODS: We have analyzed expression of vitamin D receptor (VDR), vitamin D-25-hydroxylase (25-OHase), 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-OHase), and 1,25-dihydroxyvitamin D-24-hydroxylase (24-OHase) in SCC. RESULTS: Intensity of VDR immunoreactivity was increased in SCCs as compared to normal human skin. VDR staining did not correlate with histological type or grading, nor with markers for proliferation, differentiation, or apoptotic cells. Incubation of SCC cell lines (SCL-1, SCL-2) with calcitriol resulted in a dose-dependent suppression of cell proliferation (approximately up to 30%) in vitro, as measured by a tetrazolium salt (WST-1)-based colorimetric assay. RNA levels for VDR, 25-OHase, 1 alpha-OHase, and 24-OHase were significantly elevated in SCCs as compared to HS, as measured by real-time polymerase chain reaction. CONCLUSIONS: Our findings demonstrate that modulation of VDR expression and local synthesis or metabolism of vitamin D metabolites may be of importance for growth regulation of SCCs. Additionally, SCCs represent potential targets for therapy with new vitamin D analogs that exert little calcemic side effects or for pharmacological modulation of calcitriol synthesis/metabolism in these tumors.     

Lymphatic mapping and sentinel lymphonodectomy in recurrent cutaneous squamous cell carcinomas

There are subsets of cutaneous squamous cell carcinoma (SCC), including recurrent tumours, that have a high-risk for both local recurrence and metastasis. Since the presence of regional lymph node metastases carries a poor prognosis, the early evaluation of the nodal status is crucial for staging and treatment planning. Recent trials have shown that the lymphatic mapping (LM) and sentinel lymphonodectomy (SLNE) may be successfully employed to screen nodal basins in patients with high-risk cutaneous SCCs at clinical stage N0. We report our experience with this procedure in five selected patients affected with recurrent cutaneous SCCs. A metastatic sentinel lymph node (SLN) was found in 1 of the 5 cases. No false negative result was observed. SLNE is a feasible and minimally invasive staging procedure in patients with high-risk cutaneous SCCs. It may select patients with clinically occult metastases in the regional nodal basins, who can be submitted to therapeutic lymph node dissection (LND), avoiding the morbidity of a prophylactic LND in patients without metastases in SLNs.     

Merkel cell carcinoma and multiple cutaneous squamous cell carcinomas in a patient with pityriasis rubra pilaris

A 79-year-old female was diagnosed with Merkel cell carcinoma (MCC) and multiple cutaneous squamous cell carcinomas (SCC) occurring on a background of pityriasis rubra pilaris. At the time of initial diagnosis and treatment for upper limb MCC, axillary nodal metastases were clinically evident. In the ensuing months, she developed multiple rapidly progressing SCC and eventually a left arm soft tissue deposit of metastatic MCC. Treatment involved multiple courses of fractionated radiotherapy. The salient clinical features and supporting evidence for this case are presented.     

LC3A-positive "stone-like" structures in cutaneous squamous cell carcinomas

This study was set to investigate the relation between autophagic activity and the aggressiveness of cutaneous squamous cell carcinomas (SCC), as indicated by tumor thickness and proliferative activity. The anti-LC3A antibody, recognizing both the soluble and the autophagosome-bound forms of the protein, and a standard immunohistochemical technique were applied to 75 cutaneous SCC of variable tumor thickness. The study was complemented by staining for MIB1. Three patterns of LC3A reactivity were recognized: diffuse cytoplasmic, cytoplasmic/perinuclear, and "stone-like" structures (SLS), that is, large, rounded, densely stained amorphous material, 5 μm on average, enclosed within cytoplasmic vacuoles. Higher numbers of SLS were counted in >6-mm-thick SCC compared with the intermediate-thickness tumors (2.1-6 mm) and the <2-mm-thick tumors; the mean recorded values, being 8.8, 4.55, and 1.55, respectively, were statistically significant. The diffuse cytoplasmic staining showed a nearly inverse trend, whereas the perinuclear pattern, expressed in <10% of the total, was not evaluated. With regard to MIB1 proliferation index, this increased with tumor thickness and, in linear regression analysis, was directly linked with SLS counts and inversely with the cytoplasmic pattern. These data suggest that autophagic activity in SCC, when expressed as high LC3A/SLS counts, can be regarded as an indicator of tumor aggressiveness.     

Differences in sialyl-Tn antigen expression between keratoacanthomas and cutaneous squamous cell carcinomas

Keratoacanthoma and squamous cell carcinoma are common skin tumors, especially in immunosuppressed transplant recipients, but the distinction between these two types of epidermal neoplasia may be difficult. Sialyl-Tn (Sia-GalNAc-O-Ser/Thr) is a cell surface carbohydrate associated with hyperplasia in squamous epithelium, and correlated with poor prognosis in several human adenocarcinomas. Twenty-seven keratoacanthomas and 29 cutaneous squamous cell carcinomas were examined for the expression of sialyl-Tn and of the Ki67 epitope, the latter a marker for cell proliferation. By immunohistochemistry, basaloid tumor cells at the periphery of tumor nests showed some degree of sialyl-Tn expression in 16 keratoacanthomas (59%), while only three squamous cell carcinomas (10%) showed sialyl-Tn-positive basaloid tumor cells (p<0.001). Keratinized, differentiated tumor cells were more often sialyl-Tn-positive in keratoacanthomas (89%) than in squamous cell carcinomas (31%) (p<0.001). A striking sialyl-Tn-positivity in the basal cell layer was found in a border zone directly adjacent to most tumors of both types (88 and 88%). By immunohistochemical examination of parallel sections and by double immunofluorescence, sialyl-Tn antigen expression was primarily seen in cells that did not express Ki67, although some overlap was present. Keratoacanthomas from transplant recipients did not differ in sialyl-Tn expression compared to those from non-immunosuppressed patients. The results indicate that sialyl-Tn expression is not directly related to cell proliferation, but rather to cellular features of post-mitotic cells, and that sialyl-Tn is not associated with a malignant phenotype. Sialyl-Tn may be linked to tumor regression, as seen in keratoacanthomas.     

Histopathologic features of multiple cutaneous squamous cell carcinomas of the lower extremity

Recent studies suggest cutaneous squamous cell carcinomas (SCCs) of the leg, particularly those occurring multiply in sun exposed skin of nonimmunosuppressed women, are a distinct clinical subtype. There are few reports of the histopathologic features of this subtype. A retrospective chart review of 4 patients with multiple SCCs on the leg was performed and a total of 35 biopsies from the legs examined. Histopathologically, the tumors lacked adjacent actinic keratosis (AK) and often had adjacent basaloid retiform proliferations. Most lesions (all but one) were well differentiated and about 40% could be classified histopathologically as keratoacanthoma. Perineural invasion was absent in all but one case. Using the American Joint Committee on Cancer (AJCC) staging criteria for SCC, 21 tumors were Stage I, and 9 Stage II. During 7–10 years of follow‐up, no recurrence or metastasis occurred. Patients with multiple SCCs on the lower extremities can have a range of histopathologic features, from keratoacanthoma‐like to well‐differentiated SCC.     

Complete response of advanced cutaneous squamous cell and basal cell carcinomas with sequential cemiplimab and sonidegib therapy

A 78-year-old woman was referred to our skin cancer centre with three previous incomplete resections in the left cavum conchae of a deep-infiltrating locally advanced, but still asymptomatic basal cell carcinoma (BCC). The patient noted furthermore two rapidly growing exophytic lesions in the left preauricular and cervical area in the last weeks. The clinical and histological distinction of locally advanced from metastatic cutaneous squamous cell carcinoma (CSCC) lesions was challenging. Imaging analysis with CT scans showed, however, an involvement of the parotid gland as well as multiple small lymph node metastases. The interdisciplinary tumour board decision at our institution recommended a systemic treatment with the PD1-antibody cemiplimab. After 13 cycles with cemiplimab at a dose of 350 mg intravenously every 3-weeks, the patient showed a complete response of the two CSCC lesions with histological confirmation. However, the BCC of the left ear appeared to be unchanged and still asymptomatic. The interdisciplinary tumour board considered this tumour to be no candidate for a curative resection or irradiation. Therefore, the patient was exposed to the hedgehog inhibitor sonidegib with a conventional dose of 200 mg orally per day. After 3 months of treatment, the tumour showed a markable regression and a complete response was confirmed by 3-punch biopsies from this preoperated lesion. Both cemiplimab and sonidegib were excellently tolerated with almost no adverse events apart from a mild fatigue (CTC grade 1) over the first 3 weeks of the cemiplimab therapy. There were no laboratory abnormalities found.