Proliferative Actinic Keratosis: Three Representative Cases

OBJECTIVE: This article describes a new subtype of actinic keratosis that exhibits proliferative characteristics both histologically and clinically. We describe three representative cases occuring in the presence of infiltrative squamous cell carcinoma (SCC) and/or basal cell carcinoma (BCC). METHODS: Histories of each lesion in the three cases discussed were obtained. The lesions were removed by Mohs micrographic surgery. Permanent sections, stained with hematoxylin and eosin, were examined and studied under light microscopy. RESULTS: All three lesions had failed conventional treatment with liquid nitrogen and/or 5-fluorouracil (5-FU). Histologic examination of the lesions revealed sheets of dysplastic cells growing along the basal layer of the epidermis and migrating down hair follicles and sweat ducts. An associated infiltrative SCC and/or BCC was found in each case. CONCLUSIONS: Proliferative actinic keratosis is resistant to standard therapies because of deep migration of abnormal cells along hair follicles and sweat ducts. It has a strong propensity to develop infiltrative SCC and may occur concomitantly with BCC.     

Gouty Tophi: A Squamous Cell Carcinoma Mimicker?

BACKGROUND: Digital lesions can have a broad differential diagnosis. Squamous cell carcinoma (SCC), the most common digital malignant neoplasm, must be excluded as the cause of persistent digital lesions causing nail dystrophy. OBJECTIVE: To describe a patient with a periungual hyperkeratotic lesion on the left fifth digit which, upon initial dermatopathologic examination, appeared to be a malignancy. However, on further biopsy, the lesion proved to be a gouty tophus. METHODS: Case report and literature review. RESULTS: An 84-year-old white man presented with a hyperkeratotic papule on the lateral proximal nail fold of the left fifth digit, which resulted in nail dystrophy for 1 year. Similar lesions were present on several other digits which did not affect the nail plate. Initial biopsy was consistent with actinic keratosis and was treated with cryotherapy. When the lesion persisted, repeat biopsy was performed, demonstrating fragments of squamous epithelium with focal atypia and an infiltrative growth pattern. SCC could not be excluded and the patient was referred for Mohs micrographic surgery (MMS) consultation. An excisional biopsy was performed and a white chalky material was observed at the base of the defect. Histopathology confirmed a gouty tophus. The patient was referred to his primary care physician and was treated with allopurinol. CONCLUSION: This is the first report of gouty tophus of the periungual region presenting as a hyperkeratotic lesion. Initial clinical diagnosis favored SCC and histologic evidence suggested a possible early SCC. This lesion can be confused with digital squamous cell carcinoma. The presence of pseu- docarcinomatous hyperplasia may complicate accurate diagnosis.     

Delayed Wound Healing After Three Different Treatments for Widespread Actinic Keratosis on the Atrophic Bald Scalp

BACKGROUND: Actinic keratosis is an exceedingly common premalignant lesion that can develop into squamous cell carcinoma. There is an increasing prevalence of actinic keratosis with increasing age. Numerous treatment options are available for the treatment of actinic keratosis on the scalp. Although we know that atrophic skin heals slowly, one should be careful but should not hesitate to treat. OBJECTIVE: We present three patients with widespread actinic keratotic lesions on the atrophic bald scalp who received different treatments. METHODS: Patient 1 was treated with medium-depth chemical peel, patient 2 with cryopeel, and patient 3 with CO2 laser resurfacing. In all patients, the entire surface area was treated. RESULTS: Despite the different treatment methods used, all three patients had severely delayed wound healing as a complication. Remarkably, all patients had a prolonged period of re-epithelialization. CONCLUSION: Care has to be taken in patients with widespread actinic keratosis on the atrophic bald scalp when treating the entire surface area regardless the treatment modality.     

Evaluation of the prognostic significance of follicular extension in actinic keratoses

Objective: To determine the prognostic significance of follicular extension in actinic keratosis. Design: Retrospective, case-controlled study. Setting: Mount Sinai Dermatopathology Services. Patients/participants: Out of a randomly selected pool of 1,000 biopsies, 104 cases of actinic keratosis with follicular extension and 104 cases of actinic keratosis without follicular extension were chosen for the study (56.7% male; mean [SD] age, 67.5 [11.8] years; age range, 28-93). Main outcome measures: Presence of follicular extension and location of the actinic keratosis. Age and gender of the patient. Number of previously diagnosed squamous cell carcinomas, basal cell carcinomas, and melanomas per patient. Results: Patients with follicular extension of actinic keratosis were 1.8 times more likely to have a previous history of invasive carcinoma than patients without follicular extension. Patients with follicular extension were 11 times more likely to have a previous history of invasive melanoma than patients with actinic keratoses without follicular extension. Patients with follicular extension were more likely to be male, had an older average age, and more often presented with lesions on their leg when compared to patients with actinic keratoses lacking follicular extension. Conclusion: Patients presenting with actinic keratoses with follicular extension were more likely to have increased risk factors for skin cancer. These findings have implications for identifying patient factors predictive of progression of actinic keratosis to invasive carcinoma, providing potentially valuable patient screening guidelines.     

Malignant transformation in congenital sebaceous naevi in childhood.

Sebaceous naevi are uncommon congenital skin lesions with a well-recognised potential for neoplastic change. They should be considered premalignant lesions as malignant degeneration, most commonly basal cell carcinoma and squamous cell carcinoma, occurs with a lifetime risk of between 5% and 22%. This incidence is equal to that of actinic keratosis and exceeds that of oral leukoplakia. Such change, however, is rare before puberty. Basal cell carcinoma may develop in children with naevoid basal cell carcinoma syndrome, xeroderma pigmentosum and rarely de novo but sebaceous naevus is the only solitary lesion in childhood associated with the development of basal cell carcinoma. We present two cases of malignant transformation in a congenital sebaceous naevus occurring in childhood and review the literature and discuss the evidence upon which to base management guidelines.     

Giant tricholemmal squamous cell carcinoma with cranial infiltration

Tricholemmal squamous cell carcinoma is a rare variant of squamous cell carcinoma thought to follow a more benign course. The authors present the case of a 67-year-old man with a giant tricholemmal squamous cell carcinoma on his scalp. Further investigations demonstrated a skull destruction and cranial invasion. Curative treatment was impossible, but tumor mass reduction and wound closure by sandwich split-thickness skin mesh graft transplantation using a dermal template was performed. Problems of advanced squamous cell carcinoma on the scalp are discussed.     

La photothérapie dynamique topique

Topical photodynamic therapy is the destruction of skin lesions by exposure to light after prior application of a precursor in porphyrin biosynthesis: delta-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL). Metvixia® (MAL) was recently authorized in France for the topical photodynamic therapy of actinic keratosis, superficial basal cell carcinoma (except for lesions on the face) and cutaneous squamous cell carcinoma in situ. But other indications for the use of this procedure are beginning to emerge, including other cancers (like extramammary Paget’s disease), infective and inflammatory dermatoses. Photodynamic therapy can be an effective treatment for multiple lesions with an excellent cosmetic result. In conclusion, this technique represents an interesting alternative therapy and could have a place in the management of proctological disease.     

The prognostic molecular factors in precancerous lesions and nonmelanotic skin carcinoma

The most common cutaneous carcinoma, which includes basal cell carcinoma (BCC) and squamous cell carcinomas (SCC), accounts for approximately 90% or more of all skin malignancies. Actinic keratosis, bowenoid type of actinic keratosis, Bowen's disease or SCC in situ have been considered precursors of skin SCC. Authors present the histopathological criteria of precursors of skin SCC, variants invasive SCC and BCC. Also, one discusses about the roles of immunohistochemical staining of gene products in evidence of molecular changes in cell that might occur according to the transformation from precancerous lesions to SCC.     

Predictive pathological factors of lymph nodes involvement in the squamous cell carcinoma of the penis

Objectives:To evaluate the predictive role ofprimary tumor histopathological features inpredicting inguinal lymph nodes involvement inpatients with penile squamous cell carcinoma.Material and methods:We retrospectivelyanalysed pathological records from 30consecutive patients who underwent penectomyfor invasive squamous cell carcinoma of thepenis. All histological specimens were reviewedby the same pathologist. We considered thefollowing histological parameters: histologicalgrading, growth pattern, deph invasion, tumourthickness, nuclear grading, poorlydifferentiated cancer rate, vascular andlymphatic embolization, eosinophilic andmononuclear infiltration and pathologicalstage.Results:Lymph nodes involvement occurred in 5patients who underwent `early' lymphadenectomyand in other 4 ones during oncologicalsurveillance. Lymph nodes metastasis resultedsignificantly correlated with histologicalgrading (p = 0.005), lymphatic (p = 0.005) andvenous (p = 0.02) embolization, corporacavernosa (p = 0.03) and urethra (p = 0.03)infiltration. Histological grading andlymphatic embolization were independentpredictive variables of lymph nodes involvement(p = 0.02).Conclusions:The histological grading andlymphatic embolization have to be considered asimportant parameters to select patients withpenile squamous cell carcinoma to undergo an`early' lymphadenectomy.     

光动力治疗在日光性角化病中的研究进展

日光性角化病（AK）又称光线性角化病，目前被认为是一种皮肤癌前病变，有向鳞状细胞癌转 化的风险，多见于中年以上男性，皮损多见于面部、头皮、前臂伸侧、手背等日光暴露部位。AK的发病主 要与紫外线暴露，特别是与UVB密切相关，还与性别、年龄、遗传易感性、免疫抑制相关。近年来，光动 力治疗（PDT）作为新型的治疗手段逐渐走进人们的视野，并且在AK治疗中得到了广泛应用。本文主要 综述了PDT在AK治疗中的研究进展，明确PDT在NFK治疗中的潜力和作用，并为临床实践和未来研究提 供一定指导。     

Cryopeeling (Extensive Cryosurgery) for Treatment of Actinic Keratoses: An Update and Comparison

BACKGROUND: The treatment of actinic keratoses is the most common procedure in dermatology and liquid nitrogen freezing is the most used method of destruction. Yet it is criticized for its limitations of treating only small areas and its tendency to leave hypopigmented skin. 5-fluorouracil (5-FU) treatment is also widely utilized. It has the advantage of treating large areas, but the disadvantages of length of treatment, morbidity, and only partial effectiveness in removing deep or hyperkeratotic actinic keratoses. OBJECTIVE: Long-term follow-up results are reported on the use of extensive cryosurgery to treat areas of widespread solar damage. The literature is reviewed comparing the advantages and disadvantages versus 5-FU treatment. METHODS: Three hundred and seventy-three patients were initially treated for extensive actinic keratoses in a private dermatology office in an retirement community in Florida. Individual lesions were counted under good lighting conditions with the aid of a 2.5x stereoscopic lens. The treated areas were predominately on the face and scalp areas, although some arms and hands were treated. A total of 34,604 were initially treated by spraying each individual keratosis with liquid nitrogen as well as the entire surrounding skin area. RESULTS: The data show that cryopeeling was approximately twice as effective as 5-FU when measured at 1-3 years postoperatively. In addition, the ease of application, its availability, the low cost of materials, its versatility in treating all forms of actinic keratoses, the reduced healing times, and its predictably good cosmetic results make this procedure a logical choice for treating widespread actinic keratoses. The number of squamous cell carcinoma recorded over the entire 6. 5-year study was 33 with no metastases, much lower than predicted for patients with actinic keratoses left untreated. CONCLUSION: Extensive cryosurgery (cryopeeling) is a highly effective method for removing actinic keratoses and preventing recurrences. The subsequent incidence of squamous cell carcinoma is also greatly reduced.     

Correlations among Neural Cell Adhesion Molecule, Nerve Growth Factor, and Its Receptors, TrkA, TrkB, TrkC, and p75NGFR, in Perineural Invasion by Basal Cell and Cutaneous Squamous Cell Carcinomas

BACKGROUND: Neural cell adhesion molecule; nerve growth factor; and its receptors TrkA, TrkB, TrkC, and p75(NGFR) regulate unique survival pathways in the cells of different noncutaneous malignancies exhibiting a perineural invasive phenotype. Their expression is currently unknown in basal cell carcinoma and cutaneous squamous cell carcinoma exhibiting perineural invasion. OBJECTIVE: The objective was to evaluate neural cell adhesion molecule, nerve growth factor, TrkA, TrkB, TrkC, and p75(NGFR) expression when perineural invasion occurs in basal cell carcinoma and cutaneous squamous cell carcinoma. METHODS: Four basal cell carcinomas and five cutaneous squamous cell carcinomas that were perineural invasion-positive and four basal cell carcinomas and three cutaneous squamous cell carcinomas that were perineural invasion-negative were evaluated for the expression of neural cell adhesion molecule, nerve growth factor, TrkA, TrkB, TrkC, and p75(NGFR) by immunohistochemical staining. RESULTS: For neural cell adhesion molecule, six of eight basal cell carcinomas and two of eight cutaneous squamous cell carcinomas stained positive. For nerve growth factor, seven of nine perineural invasion-positive and six of seven perineural invasion-negative tumors stained moderately or greater. For TrkA, B, and C, the perineural invasion-positive cutaneous squamous cell carcinomas generally stained darker than the perineural invasion-negative cutaneous squamous cell carcinomas. For p75(NGFR), four of five perineural invasion-positive cutaneous squamous cell carcinoma stain patterns indicated that p75(NGFR) expression was higher perineurally than elsewhere in the tumor. CONCLUSION: In basal cell carcinoma and cutaneous squamous cell carcinoma, the presence of neural cell adhesion molecule may determine tumor aggression and increased levels of nerve growth factor and TrkA, B, and C may reflect unique survival pathways. Higher levels of expression of Trk receptors in cutaneous squamous cell carcinoma cells may predict perineural invasion and the increased p75(NGFR) expression found in cutaneous squamous cell carcinoma perineurally may allow p75(NGFR) immunohistochemical staining to be used for detecting sites of perineural invasion.     

Perianal squamous cell carcinoma: A case report

Introduction and importancePerianal carcinomas, though rare, are usually squamous cell carcinoma. Current literature recommends surgical excision for tumors staged T1-T2, N0 without external anal sphincter involvement, however our case demonstrated that tumors with superficial involvement of external sphincter fibers can be resected completely.Case presentationA 45-year-old Caucasian male presented with a perianal mass found to be squamous cell carcinoma. Initial imaging suggested the anal sphincter was spared, however intraoperatively tumor cells were found involving superficial external sphincter fibers and a portion was excised to ensure complete removal.Clinical discussionPerianal squamous malignancies are often misdiagnosed as more benign conditions. Treatment aims to preserve sphincter function and depends on tumor stage along with anatomical involvement.ConclusionDespite superficial muscle infiltration, the T2N0 perianal lesion was curable with surgical resection alone without recurrence or functional deficits reported one year later. This suggests surgical management may be possible in some cases with sphincter involvement.     

An organ culture system designed to study interaction of fetal rat calvaria with human head and neck squamous cell carcinoma

The development of permanent cell lines of human head and neck squamous cell carcinoma in culture has enabled these cell lines to be used to investigate the interaction of the tumor cells with bone. After the squamous carcinoma lines on fetal rat skulls were implanted the explants with their added tumor were maintained in long-term tissue culture by use of the procedures developed for growing these tumor cells. Results confirm direct interaction with the bone by the malignant cells. Specific surface and cytoplasmic markers have been demonstrated by use of monoclonal antibodies against the tumor cells. Furthermore, tumor angiogenesis without the addition of any endogenous endothelial components has been verified. Investigations into the degree of bone infiltration and susceptibility of these interacting tumor cells to various factors, radiation therapy, and chemotherapeutic agents have been carried out. The establishment of a model system for bony invasion by squamous cell carcinoma of the head and neck permits the investigation of the mechanism of tumor invasion and the study of various potential treatment modalities.     

Signet-Ring Cell Carcinoma of the Esophagus Associated with Barrett's Epithelium: Report of a Case

We herein report a case of infiltrative esophageal signet-ring cell carcinoma resembling gastric signet-ring cell carcinoma. Grossly, the tumor was a diffusely infiltrative carcinoma involving the lower esophagus measuring 11 cm in diameter. The tumor extensively metastasized to the cervical, mediastinal, and abdominal lymph nodes, and the patient died of peritonitis and pleuritis carcinomatosa soon after undergoing a radical esophagectomy. Histologically, the tumor was signet-ring cell carcinoma covered with normal squamous epithelium. However, the most superficial part of the tumor center contained a region of Barrett's mucosa with incomplete-type intestinal metaplasia and a well-differentiated adenocarcinoma component with goblet cells. The expression of cytokeratins 7 and 20 also indicated that both the Barrett's mucosa and the signet-ring cell carcinoma had an esophageal origin. Esophageal signet-ring cell carcinoma with diffuse infiltrative growth is quite rare, and may need a special treatment strategy because of its highly aggressive behavior and poor treatment outcome.     

Condylomata acuminata and squamous cell carcinoma

Until recently, condyloma acuminatum has been considered to be a benign growth with no malignant potential. The histologically similar, yet clinically different, giant condyloma accuminatum (Buschke-Lowenstein tumor) has been defined as a mass with downward growth that has no histologic malignant changes, although the clinical course may be malignant. A review of the literature yielded 65 cases of malignant degeneration of this type of tumor and supports the concept that either condyloma acuminatum or the Buschke-Lowenstein tumor may precede or be associated with squamous cell carcinoma. A patient presenting with condyloma acuminatum in whom invasive squamous carcinoma of the penis developed exemplifies the transitory character of the disease.     

Malignant transformation of benign mixed tumor of lacrimal gland to squamous cell carcinoma 19 years after initial surgery: report of a case]

A case of malignant transformation of benign mixed tumor (pleomorphic adenoma) arising from the right lacrimal gland is reported. A 63-year-old man was referred to our clinic because of visual disturbance and protrusion of the right eye in January, 1989. His past history revealed that he had had a benign mixed tumor of the right lacrimal gland resected 19 years ago. On CT scan, an iso-density lesion homogeneously enhanced with contrast medium was found in the right orbit. This tumor was partially cystic and invaded the cranial cavity. On T1 and T2 weighted MRI, the tumor appeared as an iso-intensity area. At surgery, the tumor was subtotally resected via the combined fronto-orbital approach on February 3, 1990. Histological diagnosis of the tumor was squamous cell carcinoma, and it was construed to be a malignant transformation of mixed tumor of the lacrimal gland. Postoperatively he was placed on a course of external radiation therapy (63 Gy in total) in combination with intra-carotid Cisplatin injection therapy. The first sign of the recurrence was seen as multiple metastatic lesions in both lungs about 4 months after the surgery. In December, 1990, protrusion of the left eye and disturbance of ocular movement became progressively worse. On CT scan, recurrent metastatic tumor was seen in the left orbit and paranasal sinuses. Although additional chemotherapy and irradiation brought about a short period of symptomatic relief he succumbed to pneumonia in April 18, 1990. Metastatic squamous cell carcinoma was confirmed in the lung at autopsy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Occurrence of newly discovered human polyomaviruses in skin of liver transplant recipients and their relation with squamous cell carcinoma in situ and actinic keratosis – a single‐center cohort study

To date 14 human polyomaviruses (HPyVs) have been identified. The newly found HPyVs have not been examined with regard to post‐transplant skin carcinogenesis. To determine the occurrences in skin and possible pathological associations of the HPyVs, we studied their genoprevalences in squamous cell carcinoma (SCC) in situ or actinic keratosis and benign skin in liver transplant recipients (LiTRs); and of healthy skin in immunocompetent adults. We used highly sensitive and specific HPyV PCRs of two types. Overall, Merkel cell polyomavirus (MCPyV), human polyomavirus 6 (HPyV6), human polyomavirus 7 (HPyV7), trichodysplasia spinulosa polyomavirus (TSPyV), and Lyon IARC polyomavirus (LIPyV) were found in 58/221 (26.2%) skin biopsies. MCPyV DNA was detected in 5/14 (35.7%) premalignant vs. 32/127 (25.2%) benign skin of LiTRs, and in 12/80 (15%) healthy skin of immunocompetent adults, with no statistically significant difference in viral DNA prevalence or load. TSPyV DNA was found in a single skin lesion. LIPyV, HPyV6 and HPyV7 DNAs occurred exclusively in benign skin. Overall, the viral findings in premalignant versus benign skin were alike. The occurrences of HPyVs in skin of LiTRs and immunocompetent individuals speak against a role for any of the 14 HPyVs in SCC development.     

Imiquimod to Treat Different Cancers of the Epidermis

BACKGROUND: Topical immunomodulatory therapy with imiquimod has been recently used for the treatment of actinic keratoses, intraepithelial carcinoma, and small basal cell carcinoma (BCC) besides the licensed indication of extragenital warts (condyloma). METHODS: We treated several patients with particular epidermal neoplasias such as squamous cell cancer (SCC) and basal cell cancer of sclerodermiform type three times per week for 4 to 12 weeks. RESULTS: We report several novel aspects of the treatment of epidermal cancers with self-applied, nonpainful, immunomodulatory therapy. First, we treated-for the first time-two immunosuppressed renal transplant patients for invasive SCC with imiquimod. Interestingly, systemic immunosuppression did not adversely affect the response to therapy. Second, one patient with the high-risk and aggressive growth pattern of basal cell cancer (sclerodermiform histology) was cured from his disease at a particular location in the face, suggesting sufficient penetration despite scarring. No recurrence was detected in another patient who suffered from 29 BCCs until almost 2-years follow-up. Third, the treatment of actinic keratoses in the face is substantially shorter (in the order of 4 to 6 weeks) as opposed to other skin cancers. Immunomodulatory treatment with imiquimod led to the demarcation of in situ actinic keratosis lesions that could not be identified using the dermatologist's experience, probably because of the existence of exclusive alterations on the molecular level. CONCLUSION: Several novel aspects of immunomodulatory treatment with imiquimod and new indications such as selected cases of sclerodermiform BCC and SCC have been described. The texture of the skin at various different body locations may explain the varying sensitivities to imiquimod when facial skin is compared with skin on the extremities.