Cutaneous papillary squamous cell carcinoma. A report of two cases

Several histologic patterns of squamous cell carcinomas (SCC) have been described, including classical, adenoid, verrucous, and clear cell. We report 2 cases of an unusual purely exophytic papillary growth pattern. Both tumors occurred on sun-exposed skin of elderly patients and exhibited rapid growth. The tumors were red-tan and fungating, raising the clinical differential diagnoses of pyogenic granuloma, SCC, metastatic carcinoma or amelanotic melanoma. Histologically there was a prominent papillary growth pattern with several layers of notably atypical squamous epithelium overlying a fibro-vascular core in both cases. Mitoses were frequent. The tumors lacked deep invasion, although focal invasion of the stalk was present. These tumors were histologically distinct from verrucous carcinoma, verrucous Bowen's disease, and previously described adnexal carcinomas. The lack of deep invasion and the absence of local recurrence or metastatic disease after 18 months follow-up suggest that this histologic variant is a low-grade malignancy, although study of more cases and longer follow-up will be necessary to accurately assess the biology of this papillary variant of SCC. We believe that this growth pattern has not yet been described and a pure papillary form must be included as one of the histological subtypes of cutaneous SCC.     

Primary cutaneous myxoid spindle cell squamous cell carcinoma: a clinicopathologic study and review of the literature

Mucocutaneous squamous cell carcinoma (SCC) may rarely exhibit intracellular mucin production. Extracellular mucin production is an even rarer finding in SCC that is not well documented in the literature. Here, we report six cases of primary cutaneous and mucocutaneous SCC with prominent extracellular stromal mucin deposition and an epithelial spindle cell component. We propose the term ‘yxoid spindle cell SCC’ (MSC SCC) to describe the histologic characteristics of these six cases. We also propose a set of histologic and immunohistochemical findings for distinguishing MSC SCC from primary cutaneous and metastatic spindle cell neoplasms including other sarcomatoid carcinomas, myxoid sarcomas and the spindle cell variant of atypical fibroxanthoma (AFX). The criteria can also help discern MSC SCC from spindle cell melanomas, which may rarely show a prominent myxoid stroma. Given the small numbers of cases reported to date, the presence of prominent myxoid stroma in primary cutaneous spindle cell SCC has unknown prognostic significance at this time. Yang A, Hanley A, Velazquez EF, Cassarino DS. Primary cutaneous myxoid spindle cell squamous cell carcinoma: a clinicopathologic study and review of the literature.     

Diagnosis and follow-up of keratoacanthoma-like lesions: clinical-histologic study of 43 cases

BACKGROUND: Keratoacanthoma (KA) is easily confused with squamous cell carcinoma (SCC) on a clinical or a histopathologic basis. However, KA undergoes spontaneous regression, whereas SCC does not. OBJECTIVE: Our objective was to study the histopathologic features associated with clinical regression in KA-like lesions to support the therapeutic option. METHODS: Forty-three biopsies of KA-like lesions were taken at patient admission. One month later, surgical excision was performed in 18 growing lesions. Regressing lesions were left untreated. Classic histopathologic features and diagnosis were blindly recorded in both biopsies and surgical specimens. RESULTS: On a clinical and a histologic basis, 32 lesions were assessed as KA and 11 as SCC. Features that indicated malignancy were observed in both groups, but the probability of SCC was 31 times higher in tumors with five or more of such features. Several of the histologically atypical lesions were found to regress. CONCLUSION: SCCs and KAs have more pathologic similarities than differences, especially in the proliferative phase. The combination of the most useful features did not allow the nosologic diagnosis in difficult cases but helped. Differential diagnosis was easier to determine after the 1-month follow up. Complete surgical excision should be indicated in nonregressing and growing lesions.     

Aggressive squamous cell carcinomas in persons infected with the human immunodeficiency virus

OBJECTIVES: To illustrate the potential for aggressive growth of cutaneous squamous cell carcinomas (SCCs) in patients infected with the human immunodeficiency virus (HIV) and to determine the factors associated with increased morbidity and mortality from aggressive SCCs in HIV-infected patients. DESIGN: Retrospective nonrandomized case series. SETTING: University-based dermatologic referral center. PATIENTS: A consecutive sample of 10 patients infected with HIV who had "aggressive" SCC based on the following criteria: diameter larger than 1.5 cm, rapid growth rate, local recurrence, and/or evidence of metastasis. MAIN OUTCOME MEASURES: Morbidity and mortality. RESULTS: Five patients died of metastatic SCC within 7 years of their initial diagnosis despite treatment. Human immunodeficiency virus stage and the degree of immunosuppression were not associated with increased morbidity and mortality. Patients initially undergoing combination surgery and radiation therapy or radical neck dissection had the best outcomes. CONCLUSIONS: Patients infected with HIV can develop rapidly growing cutaneous SCCs at a young age, with a high risk of local recurrence and metastasis. High-risk SCCs should be managed aggressively and not palliatively in patients infected with HIV.     

Comparative stages of expression of human squamous carcinoma cells and carcinogen transformed keratinocytes

The mouse monoclonal antibody OSU 22-3 was prepared using cells from a squamous cell carcinoma (SCC) as an immunogen. This antibody reacts with an antigen found on squamous cell carcinomas but does not react with normal keratinocytes. This antibody and two antibodies that react with normal keratinocytes were used as markers of malignant and normal phenotypes. These markers were used to evaluate several spontaneous and carcinogen initiated SCC tumors and to identify the expression of an antigen associated with a malignant phenotype. A variety of subpopulations in carcinogen initiated tumors and spontaneous SCC tumors were noted. The subpopulations that reacted only with MoAb OSU 22-3 exhibited features of anchorage independent growth and cellular invasiveness, and formed progressively growing tumors in nude mice. Other SCC spontaneous tumor cell subpopulations reacted with the antibodies associated with normal keratinocytes. These cells did not proliferate in vitro and did not form tumors in the nude mouse. There were other carcinogen transformed cells which reacted with MoAb OSU 22-3 but not with the antibodies associated with normal keratinocytes. These cells exhibited anchorage independent growth and cellular invasiveness but did not form tumors in nude mice. We conclude from this work that human SCC tumors contain multiple cell populations. These cell populations have varied growth properties and express surface antigens that may indicate their malignant vigor. Carcinogen transformed keratinocytes do exhibit some of the characteristics of SCC tumor phenotypes but not the property of malignant progressively growing cells on a routine and consistent basis. This feature is transiently and inconsistently expressed in a surrogate host by populations prepared from spontaneous SSC tumors.     

Basal cell carcinoma in chronic arsenicism occurring in Queensland, Australia, after ingestion of an asthma medication

BACKGROUND: Ingestion of trivalent inorganic arsenic has long been recognized as a cause of basal cell carcinomas (BCCs) and has been reported most often in Taiwan and Singapore. OBJECTIVE: Our purpose was to study the clinical and histologic characteristics of BCCs occurring in Australian Caucasians as a consequence of chronic arsenicism due to ingestion of an arsenic-containing medication. METHODS: Self-referred persons with a history of ingestion of Bell's Asthma Medication were interviewed, and skin examinations were performed. Local age- and sex-matched patients with BCCs were used to compare the distribution and histologic subtypes of BCCs in arsenic-exposed and sporadic cases. RESULTS: Thirty-six persons (21 male, 15 female; mean age, 57 years) participated, all of whom had been exposed to the asthma medication early in life (mean age, 13 years) for a mean duration of 5 years. Each person had at least one cutaneous sign of chronic arsenicism, either self-reported or on examination, and all except one had a history of either BCC or squamous cell carcinoma of the skin, with self-reports of 20 to 2000 skin lesions removed per person. The mean age at first presentation with a BCC was 33 years, but neither latency nor number of skin lesions appeared to be related to duration of exposure to arsenic. BCCs in persons exposed to arsenic occurred more often on sun-protected sites compared with BCCs in age- and sex-matched sporadic cases (P <.001), but the distribution and histologic subtypes between these two groups were similar. CONCLUSION: We have described BCCs in arsenic-exposed Australians and shown that they occur predominantly in sun-protected locations. Although the reported number of skin lesions is very high, the latency and number do not appear to be related to the duration of arsenic exposure. The histologic types of the BCCs occurring in arsenic-exposed persons are not different from sporadic BCCs.     

"High single-dose'' European PUVA regimen also causes an excess of non-melanoma skin cancer

We report the results of a long-term (12.8 years) follow-up study of the detection of malignant and benign skin tumours in patients with psoriasis, who were treated with PUVA according to the European, 'high single-dose' regimen. A total of 13 squamous cell carcinomas (SCC) and 24 basal cell carcinomas (BCC) were diagnosed in 11 of 260 patients. The incidence of both SCC and BCC was increased in comparison with the general Dutch population. The ratio of SCC to BCC in the general population was 1:8 but was 1:2.5 in our study group. A positive correlation was observed between the development of SCC and the total UVA dosage, the age of the patient at the start of the PUVA treatment and a history of arsenic use. This dose-related increase in the incidence of SCC, reported in studies from the U.S.A., has not been found in earlier European studies. The average time period between the start of PUVA therapy and the diagnosis of the first malignant skin tumour was 6.0 years for SCC and 4.7 years for BCC. Among the 49 benign skin tumours were actinic keratoses, a keratoacanthoma and 'PUVA keratoses', a newly described hyperkeratotic lesion, especially found in PUVA-treated patients.     

Transformation-specific matrix metalloproteinases (MMP)-7 and MMP-13 are expressed by tumour cells in epidermolysis bullosa-associated squamous cell carcinomas

BACKGROUND: Patients with recessive dystrophic epidermolysis bullosa (RDEB) have an increased risk of developing rapidly progressive and metastatic cutaneous squamous cell carcinomas (SCC). It is unclear why these SCC behave more aggressively than sporadic SCC. Matrix metalloproteinases (MMP) are a family of endopeptidases that contribute to growth, invasion and metastasis of SCC. The role of MMP in RDEB-associated SCC is not known. OBJECTIVES: To investigate the expression of MMP-7, MMP-13 and MMP-9 in RDEB-associated SCC in comparison with sporadic SCC and Bowen's disease. METHODS: Immunohistochemical analysis of 25 RDEB-associated SCC, 61 sporadic SCC and 28 sporadic lesions of Bowen's disease was carried out using monoclonal antibodies for MMP-7, MMP-9, MMP-13 and E-cadherin and syndecan-1. RESULTS: MMP-7 was detected in all RDEB-associated SCC, in tumour cells within the invasive edge, where E-cadherin and syndecan-1 were markedly diminished or absent. MMP-7 expression was also observed in 98% of sporadic SCC and in 68% of Bowen's diseases. MMP-7 staining was significantly stronger in RDEB-associated SCC than in sporadic SCC, and was most abundant in poorly differentiated tumours. MMP-13 was detected in tumour cells in 96% of RDEB-associated SCC and in all sporadic cutaneous SCC. MMP-9 was detected in the inflammatory cells in all SCC examined. CONCLUSIONS: These results identify MMP-7 and MMP-13 as tumour cell-specific markers for SCC progression and as potential therapeutic targets in RDEB-associated SCC. The pattern of immunolabelling suggests that MMP-7 may shed E-cadherin and syndecan-1 from the SCC cell surface.     

Solar keratoses: analysis in a dermatological practice in Australia

Two hundred consecutive patients with solar keratoses (SK) seen in a private dermatology practice had on average 61.9 SK compared with eight reported in the general population. Non-melanoma skin cancer was present in 41% of patients and 17% had squamous cell carcinoma (SCC). The ratio of basal cell carcinoma to SCC in the cohort was 1.7:1. The commonest site of SK was the upper limbs but the greatest density of lesions was on the face, particularly the nose. Squamous cell carcinomas were most commonly found on the upper and lower limbs. Basal cell carcinomas were most common on the head and neck.     

Cisplatin combination chemotherapy in squamous cell carcinoma and adenoid cystic carcinoma of the skin

Seven patients with skin cancers, six with squamous cell carcinoma (SCC) and one with adenoid cystic carcinoma, were treated with cisplatin in combination with vindesine or adriamycin. Partial response was observed in three patients with squamous cell carcinomas: two cases with metastatic lung lesions and one with a primary skin lesion and lymph node metastasis. Two of the responding SCC had been resistant to previous chemotherapy, including peplomycin and mitomycin C. Multiple metastatic lesions of adenoid cystic carcinoma of the skin completely regressed after two courses of the combination chemotherapy with cisplatin and adriamycin. This report showed that cisplatin combination chemotherapy may be useful for the treatment of cutaneous squamous cell carcinoma, which is resistant to peplomycin, and adenoid cystic carcinoma of the skin.     

Clinical aspects of epidermodysplasia verruciformis and review of the literature

BACKGROUND: Epidermodysplasia verruciformis (EV), is an unusual genodermatosis characterized by persistent human papilloma virus infection with an autosomal recessive inheritance pattern. Clinically, it is characterized by flat wart-like lesions, scaly hypo- and hyperpigmented macules and/or patches, which resemble pityriasis versicolor, and development of early beginning nonmelanoma cutaneous carcinomas. METHODS: The epidemiological and clinical features of seven cases with EV that have been followed up for 5 years were included in the study. RESULTS: Seven cases consisted of four males and three females. All seven cases were working outdoors. Three cases were the product of consanguineous marriages. The onset of the lesions was between the ages of 1-20 years (the average age was 9.29 years). The initial appearance of cutaneous tumors were between the ages 15-34 years (average age: 21.28 years). Six of seven cases had malignant cutaneous tumors, of which histopathological examination revealed squamous cell carcinoma (SCC). Three of our cases had radiotherapy previously for the existing SCCs. These cases had more early malignant transformations. CONCLUSION: Radiotherapy applied against the SCC previously, together with sunlight exposure may cause early malignant transformation of skin lesions and the destructive tumors.     

Expression of vascular endothelial growth factor in basal cell carcinoma and cutaneous squamous cell carcinoma of the head and neck

BACKGROUND: Basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) can both arise from any cutaneous epithelial surface. BCC are slow growing and rarely metastasise, whereas SCC are usually more aggressive. It is likely that the angiogenic process plays a key role in determining rate of growth and propensity for dissemination. Angiogenesis is a complex process requiring many factors and a pivotal group of proteins involved in this process is vascular endothelial growth factor (VEGF). METHODS: Immunohistochemical expression of VEGF was assessed in 44 cases of BCC and 41 cases of cutaneous SCC from the head and neck region. RESULTS: VEGF was expressed by blood vessel endothelial cells in both adjacent skin and tumour, and in the basal keratinocyte layer of epidermis. In BCC, VEGF was expressed by tumour epithelial cells, predominantly at the invasive tumour front, in 24/44 cases and its expression was significantly greater than in adjacent skin (p = 0.038). More widespread VEGF expression was found in 32/41 cases of SCC, and it was significantly associated with the degree of tumour differentiation (p < 0.001). CONCLUSIONS: The patterns of VEGF expression in BCC and SCC may help to explain the different behaviour that is usually seen with these tumours.     

Skin metastasis of head and neck carcinoma predictive for dismal outcome

A 64-year-old female with locally advanced oropharyngeal carcinoma presented with an innocuous appearing macule on the abdomen. The lesion rapidly enlarged over 2 weeks into an inflammatory 5 cm fleshy nodule that was diagnosed as squamous cell carcinoma (SCC) and was found to overexpress epidermal growth factor receptor (EGFR). A fatal outcome occurred 3 months after the initial diagnosis of cancer, in spite of chemotherapy and treatment with EGFR inhibitors (cetuximab). Cutaneous metastases occur in 10 percent of squamous cell carcinomas of the head and neck. Contiguous cutaneous metastases in the head and neck areas are by far the most common. Conversely, isolated infradiaphragmatic cutaneous metastases are exceedingly rare and are associated with an aggressive clinical course. In a patient with cancer, the possibility of distant skin metastasis should be considered whenever new cutaneous nodules appear.     

Squamous cell carcinoma arising in discoid lupus erythematosus lesions of the ears infected with human papillomavirus

We describe a 51-year-old white man with discoid lupus erythematosus (DLE) of the head, neck, trunk, and upper extremities of more than 20 years' duration who developed rapidly progressive squamous cell carcinoma (SCC) of the bilateral ear helices. Human papillomavirus (HPV) was detected from excised specimens from the ears via tissue immunohistochemistry. Human papillomavirus infection of discoid lesions may be responsible for the rapid progression of SCC of this patient's bilateral ear helices.     

Topical imiquimod therapy for basal and squamous cell carcinomas: a clinical experience

Basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (SCCs) are the most common malignancies in humans. Together, they constitute approximately 95% of nonmelanoma skin cancers (NMSCs). Surgical excision remains the mainstay of therapy of low-risk NMSC, though Mohs micrographic surgery is the gold standard for high-risk NMSC. Both methods produce high cure rates, but they may not be appropriate treatments for elderly patients who are either not surgical candidates or refuse to undergo surgery for their skin cancers. Imiquimod cream 5% is a topical immune response modifier that targets the toll-like receptors 7 and 8 and up-regulates inflammatory pathways targeting diseased tissue. This noninvasive topical therapy may be more appropriate for some patients. Herein, we describe our 5-month clinical experience in mostly elderly subjects with BCC (n=21) or SCC (n= 19) who were not candidates for surgical excision and were treated with topical imiquimod. Most subjects had a history of skin cancer, and the median age of the subjects was 78 years and 79 years in the BCC and SCC groups, respectively. After biopsy alone or biopsy followed by curettage, subjects received imiquimod cream 5% once daily 5 times weekly for 6 weeks. Twenty-three BCC lesions and 22 SCC lesions were included in the analysis. Most of the 45 lesions treated were located on the head and most were in high-risk areas. Approximately 3 months after imiquimod therapy, repeat biopsies showed that only 3 (2 BCCs and 1 SCC) lesion sites had residual tumor. After a median follow-up of 26 months, there was only one additional SCC recurrence. We also present a selection of representative case studies. Imiquimod cream 5% as adjunctive therapy to curettage was safe and well-tolerated in this mostly elderly population. The improved residual tumor and recurrence rates compared with historical rates for electrodesiccation and curettage (ED&C) alone suggest that adjunctive imiquimod therapy may be an appropriate treatment option for patients who desire or require less invasive treatment for NMSCs.     

Sorafenib-induced premalignant and malignant skin lesions

Purpose To review characteristics of patients who develop premalignant and malignant skin lesions while on sorafenib therapy and discuss implications for subsequent treatment of their primary malignancies. Background Sorafenib is a newly developed multitargeted protein kinase inhibitor reported to induce a variety of adverse cutaneous effects, rarely including actinic keratoses, keratocanthomas, and squamous cell carcinomas (SCCs). Methods Published reports of individuals who have developed cutaneous lesions demonstrating atypia of the epidermis are reviewed. In addition, a 77‐year‐old man who developed not only an SCC but also verrucas within one month of taking sorafenib monotherapy for metastatic adenocarcinoma of the lung is described. Results Cutaneous lesions develop most commonly in Caucasian men older than 40 years without previous histories of skin cancer, within two weeks to three years of starting sorafenib therapy. Currently there is no definitive explanation for the relationship between sorafenib and cutaneous neoplasms. Management typically involves treatment of skin lesions with cryotherapy or excision with at least a brief discontinuation of sorafenib. In patients whose primary malignancies were responding well, sorafenib therapy was continued with close follow‐up. Conclusions The possibility of rapidly developing actinic keratoses, keratocanthomas, verrucas, and SCC during treatment with sorafenib, warrants close dermatologic follow‐up and a lower threshold for biopsy and treatment of suspicious cutaneous lesions. Development of a sorafenib‐induced SCC is not an absolute contraindication for continued use of sorafenib therapy; however, the drug should be briefly discontinued until lesions are treated.     

The Histopathologic Differentiation of Keratoacanthoma and Squamous Cell Carcinoma of the Skin

The classification of skin tumors as keratoacanthoma or squamous cell carcinoma may be difficult and, albeit rarely, lesions classified as keratoacanthoma do metastasize. In order to review the reproducibility of the pathologic classification, 100 keratoacanthomas and 100 squamous cell carcinomas of the skin were randomized and reclassified. In 81% of the keratoacanthomas and 86% of the squamous carcinomas the original diagnosis was confirmed. The presence or absence of 10 histologic criteria was recorded for all cases. Almost all of the confirmed keratoacanthomas had invaginating keratin-filled craters with epidermal proliferation at the sides and the bottom of the lesion and significant atypia and mitotic activity was rare. Most of the confirmed squamous cell carcinomas showed considerable cellular anaplasia and pleomorphism and many displayed significant mitotic activity. It is concluded that a definite diagnosis of keratoacanthoma or squamous cell carcinoma can be made objectively on histologic grounds but that some tumors are atypical or borderline lesions which must be indicated in the pathologic report.