Loss of CDKN2A and p14ARF expression occurs frequently in human nonmelanoma skin cancers.

BACKGROUND: The CDKN2A locus on human chromosome 9p21 encodes two proteins named p16INK4a and p14ARF, known to function as tumour suppressors via the retinoblastoma (Rb) or the p53 pathway. The p53 tumour suppressor gene is the most commonly mutated gene in human and mouse cancers. Disruption of the p53 and Rb pathways is a fundamental trend of most human cancer cells. Recent studies have shown that the CDKN2A gene plays an active role in the p53 and Rb tumour suppressor pathways. Genetic abnormalities in CDKN2A have been well documented in human melanoma, but their involvement in nonmelanoma skin cancer (NMSC) is less clear. OBJECTIVES: To determine whether genetic abnormalities in CDKN2A and p53 genes play a role in the development of NMSC. METHODS: We analysed 40 primary NMSCs in 40 patients (21 squamous cell carcinomas, 17 basal cell carcinomas and two actinic keratoses) for p16INK4a and p14ARF protein expression and for genetic alterations in exons 1alpha, 1beta and 2 of CDKN2A. RESULTS: Immunohistochemical analysis revealed loss of expression of p16INK4a and p14ARF proteins in 38 and 39 of 40 NMSCs, respectively. Amplification of genomic DNA by polymerase chain reaction revealed homozygous deletion of exon 1beta in 20% of tumours and of exon 2 in 82.5% of tumours. Of 22 NMSCs with p53 mutations, 13 (59%) had ultraviolet (UV) signature mutations in the p53 gene; all of them were strongly positive for p53 immunostaining. CONCLUSIONS: In addition to mutations in the p53 gene, loss of expression of CDKN2A via deletion also plays an important role in the pathogenesis of human NMSC. While p53 mutations are induced by UVB, deletions in CDKN2A could arise spontaneously, perhaps during tumour progression.

Axillary basal cell carcinoma: literature survey and case report.

BACKGROUND: Primary basal cell carcinoma (BCC) in the axilla has rarely been reported in the literature. No systematic review has yet been conducted. OBJECTIVE: To present a case of basal cell carcinoma of the axilla. This is a rare presentation of a common disease in a non-sun-exposed part of the body. METHODS: An extensive literature search for axillary BCCs was performed. An additional case is reported. RESULTS: Only 14 cases of primary axillary BCC have been reported in the literature. Metastatic axillary BCC is also rarely reported. CONCLUSION: BCC in the axilla is extremely uncommon. Factors other than sun exposure are likely involved in tumorigenesis.

Granular cell tumor treated with Mohs micrographic surgery: report of a case and review of the literature.

BACKGROUND: Granular cell tumors are uncommon soft tissue neoplasms of neural origin that most often arise in the oral cavity. Penile lesions are distinctly uncommon. Mohs micrographic surgery (MMS) is a highly effective treatment for several cutaneous neoplasms when tissue conservation is crucial. OBJECTIVE: To examine the use of MMS for this soft tissue malignancy. METHODS: We report only the eighth granular cell tumor of the penis. The literature was reviewed regarding the use of MMS for these neoplasms. RESULTS: MMS was performed to minimize the destruction of normal tissue in treating this patient's granular cell tumor. Only one previous article documented the use of MMS for this soft tissue tumor. CONCLUSION: Although utilized infrequently to treat granular cell tumors, MMS may prove beneficial when lesion location or size render tissue conservation or assuredness of cure paramount.

Single-handed needle holder loading: a safer and more efficient cuticular stitch.

BACKGROUND: Needle sticks are one of the most common and feared occupational hazards that surgeons face. OBJECTIVE: To devise a safer and more efficient suturing method. METHODS: A cuticular stitch that minimizes direct contact with the needle is described. The literature is searched for similar suturing methods. RESULTS: Decreased direct contact with the needle lowers the risk for inadvertent sticks. Efficiency is improved when superfluous steps are eliminated from the suturing technique. CONCLUSION: Single-handed needle holder loading enhances safety while optimizing efficiency during the placement of cuticular stitches.

Neglected microcystic adnexal carcinoma: the second reported case in a black patient.

BACKGROUND: Microcystic adnexal carcinoma (MAC) is a histologically aggressive appendageal neoplasm that often pursues a beguilingly indolent clinical course. MAC has previously been reported only once in a black patient. OBJECTIVE: To present the second MAC ever recorded in a black patient. METHODS: We describe a MAC of substantial dimension occurring in a black patient. The literature was subsequently examined for MAC occurring in ethnic patients. RESULTS: This MAC is remarkable not only for its occurrence in a black patient, but also because it is one of the largest MACs ever recorded (8 cm), it occurs in a relatively less common site (scalp), and its latency period before diagnosis is the longest ever definitively documented (31 years). CONCLUSION: MAC is rare among non-Caucasians. Its relatively indolent clinical growth, especially in sites that are poorly accessible to patient observation, may lead to significant delay in diagnosis and treatment.

Cutaneous metastasis of chordoma.

BACKGROUND: Chordomas are rare neoplasms that arise from the notochord remnant. They develop in the sacrococcygeal (50%) or cervical (15%) region and are generally regarded as a locally aggressive tumor with a slow progressive growth rate and a metastatic incidence ranging from 3 to 48%. Skin involvement by chordoma is rare, but can occur by direct extension, by local recurrence and by metastases. OBJECTIVE: To illustrate by a case report the clinical presentation and management of this disease. METHODS: We present a case of sacral chordoma with metastases over a 10-year period to the lungs, the soft tissue of the chest wall, the triceps tendon, and distant cutaneous metastases to the back and the nose. RESULTS: The cutaneous metastases were treated by excision. CONCLUSION: Chordoma is a slow growing tumor of the notochord remnant that may metastasize to the skin. Physicians and pathologists should be aware of this entity.

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.

Merkel cell carcinoma: spontaneous resolution and management of metastatic disease.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive, cutaneous neoplasm. The primary form of initial treatment is wide surgical excision. The use of Mohs micrographic surgery as the primary form of treatment in MCC has been controversial. The course of MCC is often aggressive, with early metastasis, widespread disease, and death. Despite the poor prognosis, spontaneous regression has occasionally been reported. OBJECTIVE: We describe the clinical course of two patients with Merkel cell carcinoma who underwent treatment with Mohs micrographic surgery for the primary MCC. Metastases were excised in the first case and spontaneously regressed in the second. Both patients are without clinical disease at the time of this report. METHODS: Histopathology, clinical records, and the current literature are reviewed. RESULTS: One patients was without recurrence of MCC for 13 years of follow-up. The other patient experienced clinical spontaneous remission after nodal spread of the disease, with no recurrence for 18 months after clinical remission and 24 months after surgery. CONCLUSION: The treatment of Merkel cell carcinoma with Mohs micrographic surgery (MMS) has been successful for the control of primary skin disease, and is at least comparable to wide excision. Spontaneous regression may occur in the course of this usually relentless and aggressive disease. The explanation for spontaneous regression of MCC is unknown.

The nasal floor transposition flap for repairing distal nose/columella defects.

BACKGROUND: Reconstruction of defects of the distal nose/columella region present a challenge both esthetically and functionally. OBJECTIVE: To describe the use of nasal floor tissue as an inferiorly based transposition flap for closure of distal nose/columella defects. METHODS: Mohs micrographic surgery for excision of basal cell carcinoma was performed on the distal nose/columella area of a patient. The resultant defect was closed using an inferiorly based transposition flap elevated from the nasal floor. Other closure options for this region are discussed. CONCLUSION: The nasal floor flap allowed the reconstruction of a properly contoured columella and distal nose.

A c-rasHa mutation in the metastasis of a human papillomavirus (HPV)-18 positive penile squamous cell carcinoma suggests a cooperative effect between HPV-18 and c-rasHa activation in malignant progression.

BACKGROUND: Human papillomaviruses (HPV) have been implicated in the etiology of anogenital squamous epithelial tumors. Of the 65 HPV strains, subtypes HPV-16 and HPV-18 frequently are associated with malignant conditions and are capable of transforming keratinocytes in vitro. However, additional cellular changes are necessary to confer tumorigenicity to HPV-infected cells. Secondary events implicated in the progression to malignancy include loss of tumor suppressor genes such as p53 and/or activation of cellular oncogenes such as c-rasHa. METHODS: Polymerase chain reaction (PCR) was used to identify HPV-16 or HPV-18 genetic sequence in primary penile squamous cell carcinoma and two inguinal lymph node metastases. p53 and c-rasHa loci were analyzed by sequencing of PCR-amplified genomic DNA. RESULTS: HPV-18 but not HPV-16 infection was found in the primary carcinoma and in inguinal metastases occurring 5 and 7 years after the initial lesion. Sequence analysis did not identify any p53 mutations in the primary carcinoma or its metastases. However, although the primary lesion and the 5-year metastasis encoded wild-type c-rasHa, the 7-year metastasis had a missense mutation within c-rasHa codon 61. CONCLUSIONS: To the authors' knowledge, this is the first report of an activating c-rasHa mutation associated with squamous cell carcinoma of the penis. The presence of activated c-rasHa in the second metastasis but not in the first metastasis or the primary lesion suggests that activation of c-rasHa may be a late event in the malignant progression of HPV-18-associated penile squamous cell carcinoma. Analysis of additional samples from primary lesions and their resultant metastases is necessary to elucidate the incidence and significance of c-rasHa activation in penile squamous cell carcinoma.

Syringoma resembling confluent and reticulated papillomatosis of Gougerot-Carteaud.

We report the case of a 31-year-old woman with a rare presentation of syringoma resembling confluent and reticulated papillomatosis of Gougerot-Carteaud. The lesions have been unresponsive to treatment with topical steroids and retinoic acid.

Pain as an atypical presentation of squamous cell carcinoma.

BACKGROUND: Cancer of the skin may be difficult to diagnose clinically if there are minimal skin findings on examination. OBJECTIVE: To remind physicians that the symptoms of squamous cell carcinoma (SCC) may precede physical signs of the tumor. METHODS: Perineural invasion of SCC was confirmed by histologic examination of surgical specimens. RESULTS: We present two patients whose initial presentation of SCC was facial pain due to extensive perineural invasion. Their diagnoses were delayed until skin lesions eventually became evident months later. CONCLUSION: Early detection can be lifesaving, thus emphasizing the importance of including skin cancer in the differential for facial pain or paresthesia.

High rate of malignant transformation in hyperkeratotic actinic keratoses.

BACKGROUND: Controversy exists over the rate of malignant transformation of actinic keratoses (AKs) and, therefore, which treatment is indicated. Furthermore, it is not known to what degree each of the separate clinical subtypes of AKs become malignant. OBJECTIVE: Our purpose was to examine clinically diagnosed hyperkeratotic AKs and classify them histologically. METHODS: Fifty papular hyperkeratotic AKs on the dorsum of the hand, wrist, and arm, less than 1 cm in diameter, were identified in 43 patients. Histologic evaluation was conducted in a blinded fashion by two observers. RESULTS: Histologic examination showed 18 lesions (36%) to be invasive squamous cell carcinoma, whereas another seven (14%) were squamous cell carcinoma in situ. Proliferative AKs were the next most common lesion identified (26%), followed by hypertrophic (10%) and lichenoid (4%) AKs. Basal cell carcinomas (4%) and other benign lesions (6%) comprised the rest of the biopsy specimens. CONCLUSION: It is possible to predict clinically, with greater certainty than previously realized, which AKs have a greater tendency toward malignant change. Clinical hyperkeratotic AKs less than 1 cm in diameter on the dorsum of the hand, wrist, or forearms of white patients have a malignancy rate of 50%. Lesions with this clinical description should be removed by shave biopsy, then by 35% trichloroacetic acid, then liquid nitrogen to a width and depth of 3 mm.

Repair of defects of the nasal ala.

BACKGROUND: Alar defects present a reconstructive challenge. OBJECTIVE: To define closure options for alar defects of variable thickness and location. METHODS: The repair options for closure of alar defects are reviewed and discussed with regard to depth of defect and complexity of reconstruction. CONCLUSION: Surgeons repairing defects of the nose should develop a variety of reconstructive approaches for the ala including but not limited to those presented here.

An assessment of the suitability of Mohs micrographic surgery in patients aged 90 years and older.

BACKGROUND: One option for the treatment of cutaneous tumors in the very elderly has been simple observation. However, the combination of an increasing elderly population and a concomitant high incidence of skin cancer will make this problem more common. OBJECTIVE: To assess the suitability of Mohs micrographic surgery as a treatment modality for skin cancer in the 90 years and older age group. METHODS: A group of patients who underwent Mohs surgery from January 1988 to August 1996 aged 90 years and older was identified, and tumor type, site, comorbid medical conditions, medications, and surgical complications were recorded. RESULTS: A total of 106 basal cell carcinomas (BCCs), 33 squamous cell carcinomas (SSC), six melanomas, and one basosquamous carcinoma were resected from 115 patients with an average age of 92.4 years. The overall ratio of BCC/SCC was 3.2 BCCs occurred most commonly on the face; SCCs were found more frequently on the cheeks. Patients had an average of 1.9 comorbid medical conditions and took an average of 2.3 regular medications. One complication occurred. CONCLUSION: Mohs surgery is a safe and effective therapy for those over 90 years of age.