Topibal nitrogen mustard induced carcinogenesis.

Mycosis fungoides is a rare malignant lymphoma that primarily affects the skin. Lymph node and visceral involvement may follow. The disease is chronic in course, displaying numerous clinical variations. Two cases of mycosis fungoides complicated by the development of cutaneous squamous cell carcinoma will be discussed. One of the two patients developed metastatic squamous cell carcinoma from an initial primary cutaneous lesion. Both patients were treated for long periods with topical nitrogen mustard in addition to systemic therapy. The question of topical nitrogen mustard induction of squamous cell carcinoma is raised.     

Aggressive intranasal carcinoma mimicking infection or inflammation

In a twenty-year period we have treated five patients with intranasal squamous cell carcinomas who initially were thought to have benign cutaneous disorders of the nasal skin. Advanced squamous cell carcinoma requiring total rhinectomy, often with extensive contiguous midface excision, was found in all patients. Three of these five patients died of their disease. In one patient, a red nose resembling acne rosacea was present. In the four others, chronic cellulitic or ulcerative cutaneous involvement was caused by squamous cell carcinoma. These cases emphasize the need for intranasal examination and appropriate radiologic studies to exclude intranasal carcinoma in patients with apparently unresponsive cutaneous nasal disease.     

Sunlight-skin cancer association in the dog: A report of three cases

Squamous cell carcinoma is one of the most frequently recognized neoplastic diseases of the canine integument, although few risk factors influencing tumor development have been clearly defined. Three dogs with cutaneous squamous cell carcinomas are reported. Tumors developed in lightly-pigmented, glabrous following chronic sunlight exposure and long period of dermatosis. Microscopic examination of tissues from the three dogs showed progressive development of epithelial hyperplasia through stages of solar keratosis-like lesions to invasive and metastatic squamous cell carcinoma.     

Cutaneous squamous cell carcinoma of the lower limbs in Goiânia, Goiás, Brazil

BACKGROUND: Cutaneous squamous cell carcinoma is a common malignant neoplasm that affects areas that are exposed to the sun in fair-skinned people. It occurs less frequently on the lower limbs where other etiological factors are involved. OBJECTIVE: To determine the epidemiological aspects of cutaneous squamous cell carcinoma of the lower limbs in Goiania. METHODOLOGY: Forty-three cases of cutaneous squamous cell carcinoma of the lower limbs from the Cancer Registry of the Population Base of Goiás, for the period between 1995 and 1999, were included in the study. RESULTS: Among the cases of cutaneous squamous cell carcinoma registered in this 5-year interval, 43 (4.6%) represented cases affecting the lower limbs. Of these individuals, seven (16.3%) were male and 36 (83.7%) female (P < 0.001). Those in the age group of 60 years and above represented 90.7% of the cases (P < 0.001). None of the patients had metastasis. CONCLUSION: Cutaneous squamous cell carcinomas on the lower limbs are more frequently seen in women older than 60 years of age, and they rarely metastasize.     

Parotideal lymph node metastasis in squamous cell carcinoma of the skin

BACKGROUND: Metastatic involvement of the parotideal lymph nodes from cutaneous squamous cell carcinoma is rare in occurrence, but has a high prognostic value. The aim of the present study was to define a patient group with a high risk for development of regional metastasis and to determine the follow-up course and therapy of metastasis in these patients. MATERIAL AND METHODS: Nineteen patients treated with malignancies of the parotid gland over a time period of four years were analyzed prospectively. RESULTS: In 6 out of 19 patients the parotideal tumor proved to be a lymph node metastasis of previously treated poorly differentiated squamous cell carcinoma of the skin. The diameter of the primary tumor was at least 1.5 cm in 5 out of 6 cases. The time interval between detection of metastatic involvement of the parotid gland and diagnosis of a preexisting skin cancer was approximately 7 months. Metastastic infiltration of cervical lymph nodes could be shown in 4 patients. In one patient pulmonary metastases were detected. CONCLUSION: On the basis of data from the literature and the results presented here, patients who are at high risk for regional metastasis were defined. Clinical examination of the parotid gland and cervical lymph nodes should be performed frequently in these patients at least for 18 months after primary tumor diagnosis. Parotideal lymph node metastases of a squamous cell carcinoma of the head skin should have similar treatment to primary squamous cell carcinoma of the parotid gland provided that a curative option exists.     

Cutaneous malignancy and human immunodeficiency virus disease

Certain skin cancers occur with increased frequency or altered course in patients infected with HIV. Malignant melanoma and squamous cell carcinoma are examples of cutaneous malignancies that have a more aggressive course in patients with HIV. Others, such as basal cell carcinoma, appear more frequently in this population but do not appear to be more aggressive. The incidence of HIV-associated Kapsosi's sarcoma has markedly decreased since the advent of HIV antiretroviral therapy. Our understanding of the pathogenesis of this malignancy and its unique management issues are fully reviewed. Cutaneous T-cell lymphoma (CTCL) is rare in this population. Other types of cutaneous lymphoma and HIV-associated pseudo-CTCL are discussed. This article addresses prevention, treatment, and follow-up strategies for this at-risk population. LEARNING OBJECTIVE: At the completion of this learning activity, participants should be familiar with the unique epidemiology, clinical course, and management of cutaneous malignancy in patients infected with HIV.     

Human papillomavirus infection and skin cancer risk in organ transplant recipients

Warts and squamous cell carcinomas are important cutaneous complications in organ transplant recipients. The role of infection with human papillomaviruses (HPV) in the development of cutaneous squamous cell carcinoma is still unclear. An extremely diverse group of HPV types, mainly consisting of epidermodysplasia-verruciformis (EV)-associated HPV types, can be detected in benign, premalignant, and malignant skin lesions of organ transplant recipients. Frequently, there are multiple HPV types present in single skin biopsies. Typically, the prevalence of viral warts rises steadily after transplantation and a strong association exists between the number of HPV-induced warts and the development of skin cancer. The interval between the transplantation to the development of warts is clearly shorter than the interval from transplantation to the diagnosis of the first skin cancer. A comparison of transplant recipients with and without skin cancer, however, showed an equally high prevalence of EV-HPV DNA in keratotic skin lesions in both groups of patients and the detection rate and spectrum of HPV infection in hyperkeratotic papillomas, actinic keratoses, and squamous cell carcinomas was also similar. HPV DNA can frequently be detected in patients with hyperproliferative disorders like psoriasis and antibodies against HPV in patients with regenerating skin (e.g., after extensive second degree burns). Latent infection with EV-HPV seems to be widespread. The hair follicle region might be the reservoir of EV-HPV. The E6 protein from a range of cutaneous HPV types effectively inhibits apoptosis in response to UV-light induced damage. It is therefore conceivable that individuals who are infected by EV-HPV are at an increased risk of developing actinic keratoses and squamous cell carcinomas, possibly by chronically preventing UV-light induced apoptosis.     

Risk factors for squamous cell carcinoma of the skin with two illustrative cases and literature review

Non-melanoma skin cancers, including basal cell carcinoma and squamous cell carcinoma are most frequently observed neoplasms worldwide. Their incidence has steadily been growing. Cutaneous squamous cell carcinoma is more common than basal cell carcinoma in dark complexion individuals. Every year, more than one million new cases of non-melanoma skin cancers (NMSC) are identified in the United States, which is roughly estimated to account for 50% of all cancers in this country. In this article, two illustrative cases are presented, which demonstrate the risk factors for cutaneous squamous cell carcinoma development, emphasizing the relationships and synergistic interactions in the process of carcinogenesis.     

Human papillomavirus type 16 in a homosexual man. Association with perianal carcinoma in situ and condyloma acuminatum.

BACKGROUND--The association of anal carcinoma with human papillomavirus (HPV) type 16 infection is well documented. Anal carcinoma is also frequently associated with a history of anogenital condylomata. More than 90% of anogenital condylomata contain HPV type 6 or 11. It is rare for a condylomatous lesion to contain HPV 16. We report the unusual case of a homosexual man, testing positively for human immunodeficiency virus, with carcinoma in situ evolving within perianal condylomata infected with HPV 16. OBSERVATIONS--Microscopic examination of tissue specimens from ulcerated verrucous lesions on the perianal mucosa revealed changes of classic condylomata acuminata with contiguous focal squamous cell carcinoma in situ. Testing for HPV DNA by in situ hybridization identified HPV 16 in both the condylomatous and carcinoma in situ areas. CONCLUSIONS--The association of HPV 16-infected condylomata and adjacent carcinoma in situ implies that cutaneous genital condylomata may progress to high-grade lesions. Given that homosexual men are at high risk for perianal carcinomas, HPV typing of perianal condylomata specimens may help identify immunocompromised patients who are at risk for the development of carcinomas.     

Invasive squamous cell carcinoma with sporotrichoid metastasis in a patient with cutaneous T cell lymphoma treated with chronic extracorporeal photopheresis.

An 83-year-old Caucasian man with cutaneous T-cell lymphoma developed an aggressive squamous cell carcinoma of the left forearm, which recurred and metastasized after Mohs micrographic surgery and systemic chemotherapy with cis-platin and 5-fluorouracil. He was treated with extracorporeal photopheresis, radiation therapy, PUVA photochemotherapy, and interferon therapy for cutaneous T-cell lymphoma. Aggressive squamous cell carcinoma can occur in the setting of extracorporeal photopheresis.     

Secondary malignant neoplasms in 71 patients with Sézary syndrome

BACKGROUND: Sézary syndrome (SS) is characterized by a malignant proliferation of CD4+ve T cells, which may result in a degree of immunoparesis. Immunosuppression is associated with an increased incidence of internal malignant neoplasms and a high rate of nonmelanoma skin cancer, particularly squamous cell carcinoma. Therefore, we reviewed the incidence of secondary malignant neoplasms in patients with SS. OBSERVATIONS: Of 71 patients with SS, 16 (23%) developed 19 secondary and tertiary malignant neoplasms. These malignant neoplasms included 8 cutaneous squamous cell carcinomas, 2 squamous cell carcinomas of the oral mucosa, and 9 other internal malignant neoplasms. The incidence of internal malignant neoplasms was twice that reported in patients of similar age treated for Hodgkin disease (P = .02). Furthermore, the incidence of cutaneous squamous cell carcinoma in the cohort was 42 times that observed in a study conducted in England of an age-matched population (1657 per 1 x 10(5) vs 39 per 1 x 10(5) person-years [95% confidence interval, 626-2856]). CONCLUSIONS: A number of therapeutic modalities for SS are known to be carcinogenic. We compared the different therapeutic modalities received by our patients and found no significant difference between the total cohort of patients with SS and the patients who developed secondary malignant neoplasms. These data indicate that the high incidence of secondary malignant neoplasms in patients with SS is due, at least in part, to the disease itself. The clonal proliferation of CD4+ve T cells and the relative lymphopenia (compared with a healthy population) of nonneoplastic T cells may result in compromised immunosurveillance, so that early neoplasia, whether arising spontaneously or as a result of therapy, are not dealt with appropriately.     

Treatment of cutaneous squamous cell carcinomas by intralesional interferon alfa-2b therapy.

BACKGROUND AND DESIGN--Intralesional recombinant interferon alfa-2b has been shown to be effective in the treatment of actinic keratoses and basal cell carcinomas. This open-label study was designed to evaluate the effectiveness and cosmetic result of this therapy on actinically induced, primary cutaneous squamous cell carcinomas. Thirty-six squamous cell carcinomas (28 invasive lesions and 8 in situ lesions) ranging in size from 0.5 to 2.0 cm in the longest dimension were treated with interferon alfa-2b 1.5 million units injected intralesionally three times per week for 3 weeks. Eighteen weeks following therapy, the treatment sites were excised and examined for histologic evidence of remaining tumor. RESULTS--Thirty-three (97.1%) of 34 evaluable lesions revealed an absence of squamous cell carcinoma histologically after therapy, although three biopsy specimens (8.8%) obtained after treatment showed actinic keratoses, for an overall complete response rate of 88.2%. The lesion not eliminated after treatment was an invasive squamous cell carcinoma. The investigators and patients independently judged 93.9% of cases to have a very good or excellent cosmetic result. Adverse reactions were limited to those influenzalike symptoms well recognized to occur with interferon therapy and these were well tolerated. Only one patient discontinued therapy due to side effects. CONCLUSIONS--This trial demonstrates that intralesional interferon is effective in the treatment of small sun-induced squamous cell carcinomas with well-tolerated side effects and a highly acceptable cosmetic result.     

Cutaneous squamous cell carcinomas and papillomaviruses in renal transplant recipients: a clinical and molecular biological study.

Papillomaviruses are strongly implicated in squamous cell carcinomas arising on mucosal surfaces of normal individuals, and in the skin carcinomas of epidermodysplasia verruciformis suffers. Renal transplant recipients often have numerous skin warts and, in Australia particularly, a very high risk of developing cutaneous squamous cell carcinoma. To determine the magnitude of this risk, and to test whether papillomaviruses are specifically associated with these cancers, we examined 188 renal transplant recipients for skin cancers and tested 235 biopsy specimens of (histologically proven) squamous cell carcinomas for the presence of viral DNA. The risk of developing squamous cell carcinoma increased with duration of transplant: the probability being 25% after 9.5 years (standard error = 1.3 years) rising to 50% at 20.6 years (standard error 6.8 years). Factors which did not appear to affect the risk of tumour development included the patients sex and their skin type. However the age at transplant significantly altered the risk with patients transplanted at greater than 35 years developing tumours about four times more rapidly than patients less than or equal to 35 years. Extensive hybridisation tests for the presence of papillomavirus DNA in squamous cell carcinomas were negative, as was the polymerase chain reaction amplification method using general L1 gene oligonucleotide primers. Our data do not support a role for papillomavirus in the maintenance of cutaneous squamous cell carcinoma.     

High‐risk cutaneous squamous cell carcinoma in a Japanese allogeneic bone marrow transplant recipient on long‐term voriconazole

Cutaneous squamous cell carcinomas arise as secondary cancers in hematopoietic stem cell transplant survivors. They have been documented primarily in Western cohorts and relatively little is known about their occurrence in Asian hematopoietic stem cell transplant recipients, with no reports of squamous cell carcinomas with high‐risk features in Asian patients. We describe a case of a cutaneous squamous cell carcinoma with high‐risk features on the scalp of a Japanese bone marrow transplant recipient approximately 6.5 years post‐transplant, who was on long‐term voriconazole. The history of a photodistributed erythema followed by the appearance of multiple actinic keratoses and solar lentigines, together with the rarity of cutaneous squamous cell carcinomas in Asian hematopoietic stem cell transplant cohorts revealed in our literature review, suggest that voriconazole use contributed to the development of high‐risk squamous cell carcinoma in our patient.     

European guidelines for topical photodynamic therapy part 2: emerging indications – field cancerization,photorejuvenation and inflammatory/infective dermatoses

In addition to established indications in non‐melanoma skin cancer in immunocompetent patients, photodynamic therapy (PDT) has been studied for the treatment, and possible prevention, of superficial skin cancers in immunosuppressed patients. As a topical photosensitizer can be applied over large areas, PDT is also increasingly used for field cancerization in photodamaged skin, with evidence of potential to delay the development of actinic keratoses and basal cell carcinoma, although direct evidence of prevention of invasive squamous cell carcinoma remains limited. PDT has been studied in patch/plaque‐stage cutaneous T‐cell lymphoma, with efficacy more likely in unilesional disease. Accumulating evidence supports the use of PDT in acne and several other inflammatory/infective dermatoses including cutaneous leishmaniasis, although protocols are still to be refined. Despite proven efficacy, PDT is not widely used in viral/genital warts, where pain during treatment can be intense. PDT is a therapeutic option for photorejuvenation, with improvement in fine wrinkles, mottled hyperpigmentation, roughness and sallowness reported.     

Emerging dermatologic issues in the oncology patient

The spectrum of skin diseases that occurs in the oncology patient differs somewhat from that seen in other immunosuppressed populations. We review the cutaneous manifestations of invasive mold infections in the leukemia/lymphoma population. Aspergillus mold infections are now the leading infectious cause of death in this population. We also review the pustular eruption caused by a new class of chemotherapy for solid malignancies. An update on cutaneous graft-versus-host disease appears elsewhere in this journal. Cutaneous squamous cell carcinomas and basal cell carcinomas occur more frequently in the chronic lymphocytic leukemia and non-Hodgkin's lymphoma population; this is discussed, as is the more aggressive clinical course of these tumors.     

Primary cutaneous adenosquamous carcinoma: a case report and review of the literature

BACKGROUND: Adenosquamous carcinoma (ASC) of skin is a rare but distinctive neoplasm that usually exhibits an aggressive course. To date, 13 well-documented and undisputed cases of primary cutaneous ASC have been reported. This term has been used for tumors with better prognosis, such as mucoepidermoid carcinomas and acantolytic squamous cell carcinomas, originating confusion. We report a primary cutaneous ASC and review the literature. METHODS: In this report a woman with primary ASC of the skin was studied. Histopathological examination and immunohistochemical stains were performed. RESULTS: The tumor had two components: conventional squamous cell carcinoma merging with adenocarcinoma. After a local recurrence and lymph node metastases, the patient has no evidence of disease 8 months later. CONCLUSIONS: Pathologists should reserve the term ASC for tumors exhibiting the above mentioned appearance. In such circumstances, a metastatic origin must always be excluded.     

Somatic mutations of Fas (Apo-1/CD95) gene in cutaneous squamous cell carcinoma arising from a burn scar

Fas (Apo-1/CD95) is a cell-surface receptor involved in cell death signaling, and recent reports have suggested that defects within the Fas receptor pathway such as Fas mutation play an important part in the development and progression of human tumors. Burn scar-related squamous cell carcinoma of skin is a unique subtype of cutaneous squamous cell carcinoma, and tends to be more aggressive in nature than conventional squamous cell carcinoma. The molecular mechanisms underlying the development and progression of burn scar-related squamous cell carcinoma, however, are not clear. In this study, we analyzed the entire coding region and all splice sites of the Fas gene for the detection of the somatic mutations in a series of 50 conventional squamous cell carcinomas and 21 burn scar-related squamous cell carcinomas by polymerase chain reaction, single strand conformation polymorphism, and DNA sequencing. We detected mis-sense mutations in three of 21 burn scar-related squamous cell carcinomas (14.3%), whereas no mutation was detected in 50 conventional squamous cell carcinomas. Of the three Fas mutations detected in the burn scar-related squamous cell carcinomas, one was found in Fas ligand-binding domain, another one was identified in the death domain known to be involved in the transduction of an apoptotic signal, and the other one was found in the transmembrane domain. Our data show that some burn scar-related squamous cell carcinomas have Fas gene mutations in important regions for the apoptosis function and suggest that these mutations might be involved in the pathogenesis of burn scar-related squamous cell carcinomas. In addition, our results provide an important clue to understanding the difference between burn scar-related squamous cell carcinoma and conventional squamous cell carcinoma at the molecular level.     

Absence of human herpesvirus 8 and Epstein-Barr virus genome sequences in cutaneous epithelial neoplasms arising in immunosuppressed organ-transplant patients

Recent studies have implicated herpesvirus 8 and Epstein-Barr virus in the development of cutaneous malignancies in immunosuppressed patients. In order to examine the strength of this association, we examined 37 malignant, pre-malignant and benign cutaneous epithelial neoplasms removed from immunosuppressed organ recipients for the presence of human herpesvirus 8 and Epstein-Barr viral genome sequences using polymerase chain reaction (PCR) and in situ hybridization. We examined 2 actinic keratoses, 1 benign keratosis, 11 invasive squamous cell carcinomas, 17 squamous cell carcinomas in situ and 6 basal cell carcinomas. We also examined 4 basal cell carcinomas, 1 invasive squamous cell carcinoma and 3 squamous cell carcinomas in immunocompetent hosts. In contrast to findings reported by other investigators, we were unable to detect viral genome sequences in any of the biopsies examined. Our findings suggest that human herpesvirus 8 and Epstein-Barr virus likely do not play an etiologic cogenesis in immunocompromised patients.     

Occurrence of Hodgkin's disease and cutaneous B-cell lymphoma in the same patient: a report of two cases

The occurrence of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) in the same patient is well known. The most frequent observation has been the development of large B cell lymphoma in patients affected with the nodular form of lymphocytic predominant HD. A less common situation is the development of NHL among patients successfully treated for HD. In such patients the second lymphoma has been thought to be related to the previous therapy or the immunodeficiency state that can accompany HD. Histologically, these NHL lymphomas often are intermediate to high grade and frequently extranodal. We report two patients successfully treated for HD who also developed NHL of the skin. Both patients presented with strikingly similar findings regarding to sex, age and subtype of HD. Clinical, histopathological and immunophenotypical findings were consistent with cutaneous low-grade B cell lymphoma of the marginal zone type. Both cases remain in complete remission of HD after standard therapy. In both patients the cutaneous lymphoma followed an indolent clinical course after a long follow-up period. This observation expands the spectrum of alterations possibly related to HD.