Progressive decreases in nuclear retinoid receptors during skin squamous carcinogenesis.

Retinoids are essential for normal skin growth, differentiation, and apoptosis and are active pharmacologically in the prevention and treatment of skin cancers and other lesions. Retinoid effects are mediated mainly by retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which act as transcription factors to alter gene expression. Using in situ hybridization, we analyzed the expression of RARs and RXRs in normal sun-exposed skin (n = 85), squamous cell carcinoma (SCC; n = 28), and actinic keratosis [AK (a precursor to SCC); n = 38]. The expressions of five receptors (RAR-alpha and -gamma and RXR-alpha, -beta, and -gamma) were moderate to very strong in normal skin, with higher expressions in spinous and granular layers than in the basal layer. RAR-beta expression was weak or absent in normal and lesion samples. All five receptors expressed in the skin were suppressed progressively from normal skin to premalignant skin (AK) to invasive skin SCC. Specific receptor decreases in lesions relative to normal skin ranged from 75% (RXR-beta) to 96% (RAR-alpha) in SCC and from 37% (RAR-gamma) to 68% (RXR-beta) in AK. The degree of suppression of RXR-alpha and RAR-gamma, the two predominant retinoid receptors in skin, was relatively less for RXR-alpha (58% versus 86%; P = 0.015) and relatively greater for RAR-gamma (37% versus 89%; P = 0.0001) between AK and SCC, suggesting that suppression of RXR-alpha may be an earlier event and expression of RAR-gamma may be a later event of multistep squamous skin carcinogenesis. Our results indicate that suppressed expression of retinoid receptors occurs early (in AK) and is associated with progression of squamous skin carcinogenesis to SCC.

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.

Fine needle aspiration diagnosis of transitional cell carcinoma metastatic to the brain. A case report.

BACKGROUND: Transitional cell carcinoma (TCC) rarely metastasizes to the brain. In this case, aspiration of a cystic brain lesion was performed and a cytologic diagnosis made. To the best of our knowledge, this is the first reported case of TCC metastatic to the brain diagnosed by fine needle aspiration. CASE: A 72-year-old male with a past medical history of invasive TCC, colonic adenocarcinoma and prostatic adenocarcinoma presented with a large, right, temporal, cystic mass. Fine needle aspiration was performed intraoperatively, and a cytologic diagnosis of metastatic TCC was rendered and confirmed by subsequent tissue examination. CONCLUSION: Intraoperative fine needle aspiration of cystic tumors can be useful in identifying the primary site. The cytologic features of intracerebral metastatic TCC can differ significantly from those observed in urinary tract specimens of high grade TCC. A predominance of large fragments of malignant cells with numerous mitotic figures and apoptotic bodies was seen in the former. The background showed high grade, single transitional cells similar to those observed in urinary tract samples of TCC.

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.

Expression of the human erythrocyte glucose transporter Glut1 in cutaneous neoplasia.

BACKGROUND: The increased glucose uptake seen in cancer cells correlates with the expression of human erythrocyte glucose transporter (Glut1) protein in certain human malignancies. OBJECTIVE: Our purpose was to determine Glut1 expression in cutaneous neoplasms. METHODS: A polyclonal anti-Glut1 antibody (MYM) and a standard ABC immunoperoxidase technique were used to determine Glut1 expression in invasive squamous cell carcinomas (SCCs), SCC in situ, basal cell carcinomas (BCCs), melanomas, actinic keratoses (AKs), seborrheic keratoses, common acquired nevi, and scars with regenerative epidermal hyperplasia. RESULTS: All of the cases of SCC in situ, 14 of 15 (93%) of the SCC, and 13 of 15 AKs (87%) showed intense membranous staining for Glut1. Glut1 staining was present in the epidermis of 8 of 15 scars (53%) but was not detected in any BCC, even in areas of focal keratinization and squamous metaplasia. Glut1 reactivity was absent in the melanomas and seborrheic keratoses. CONCLUSION: Glut1 expression in a cutaneous lesion strongly suggests a proliferative lesion of the squamous cell type.

A pilot study comparing toluidine blue and hematoxylin and eosin staining of basal cell and squamous cell carcinoma during Mohs surgery.

BACKGROUND: Hematoxylin and Eosin (H&E) is the most common stain used for Mohs frozen sections. Toluidine blue (T-blue) is a metachromatic stain that has been frequently utilized for this purpose. OBJECTIVE: To compare the cytologic and stromal staining patterns of each stain for Mohs frozen sections of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), and to identify the advantages and disadvantages of each technique. RESULTS: T-blue revealed stromal change associated with the presence of BCC and SCC. H&E provided more prominent visibility of individual cell keratinization and necrosis, which are common features seen in SCC. CONCLUSION: We found T-blue to be fast and effective in identifying mucopolysaccharides in stroma associated with basal cell carcinoma. For this reason, T-blue is our preferred stain for BCCs, while H&E can provide greater ease of identification of histologic features of SCCs.

Desmoplasia and neurotropism. Prognostic variables in patients with stage I melanoma.

BACKGROUND: Desmoplastic melanomas with and without neurotropism are thought to be more clinically aggressive than other melanomas of comparable thickness. This study evaluates the prognostic significance of desmoplasia and neurotropism in Patients with Stage I cutaneous melanoma completely excised at the initial presentation of disease and prospectively studied for a minimum of 8 years. METHODS: Desmoplasia and neurotropism were evaluated as single prognostic predictors in survival outcome of cutaneous Stage I melanomas and as variables in the University of Pennsylvania Pigmented Lesion Study Group 8-year survival model for Stage I melanoma. In addition, the clinical presentation and follow-up of melanomas with desmoplasia and/or neurotropism was compared with that of other types of cutaneous Stage I melanoma in patients also followed for a minimum of 8 years. RESULTS: Neurotropism was associated with a statistically significant decrease in survival in patients with melanomas with desmoplasia. A decrease in survival also was observed in other types of melanoma with neurotropism, but the difference was not statistically significant. Melanomas with neurotropism had a statistically significant increase in local recurrence. Desmoplasia was not associated with a statistically significant decrease in survival. CONCLUSION: Desmoplasia is not associated with a statistically significant decrease in the prognosis of patients with primary cutaneous Stage I melanoma. The more clinically aggressive behavior of desmoplastic melanomas observed in previous studies may be secondary to initial misdiagnosis and/or inadequate margin assessment of these lesions. Neurotropism, however, is associated with a statistically significant decrease in survival in patients with desmoplastic melanomas and is most likely associated with decreased reduces patient survival in other melanoma types. Neurotropism is also related to an increase in the frequency of local recurrence of melanoma.

Invasive fungal dermatitis in the < or = 1000-gram neonate.

OBJECTIVE: In 1991, we noted the emergence amongst our extremely low birth weight neonates of a new clinical entity, invasive fungal dermatitis, characterized by erosive, crusting lesions and a high rate of subsequent systemic fungal infection. We sought to define this condition and examine potential risk factors. METHODS: Sixteen neonates with invasive fungal dermatitis were seen during a 2-year period in three Baylor College of Medicine affiliated intensive care nurseries. Seven were confirmed cases, with skin biopsy evidence of invasion beyond the stratum corneum. Nine had a consistent clinical course and a positive potassium hydroxide examination of skin scrapings or isolation of fungi from skin or systemic cultures. Three controls were matched to each case by hospital, date of admission, and birth weight. Data was collected by retrospective chart review. RESULTS: Invasive fungal dermatitis occurred in 5.9% of at-risk infants. Case patients had a mean birth weight of 635 g and developed skin lesions at a mean age of 9 days (range, 6 to 14). Candida albicans was the most commonly implicated pathogen, but other Candida species, Aspergillus, Trichosporon beigelii, and Curvularia were also seen. Disseminated infection occurred in 69%, all due to Candida sp. Case patients were significantly more premature than controls (mean gestation, 24.4 vs 25.9 weeks) and were more likely to be delivered vaginally (81% vs 50%). Postnatal steroids were administered to cases (81%) more often than controls (46%). Case patients had more prolonged hyperglycemia (as assessed by insulin administration) than controls (mean 4.3 vs 2.0 days). CONCLUSIONS: Invasive fungal dermatitis is a disease of the smallest, most immature neonates and is associated with vaginal birth, steroid administration, and hyperglycemia. We speculate that the skin serves as a portal of entry for colonizing fungal species and may thus lead to disseminated infection. Methods to improve skin barrier function may be useful in preventing this disorder.

Phagocytosis by zippers and triggers.

Two mechanisms have been considered for particle phagocytosis. According to the zipper mechanism, ingestion occurs by sequential engagement of a phagocyte's membrane against the particle surface, and pseudopod advance proceeds no further than receptor-ligand interactions permit. In contrast, in the trigger mechanism particle binding initiates an all-or-none phagocytic response. Although the weight of experimental evidence has favoured the zipper mechanism, recent observations of bacterial entry into epithelial cells and macrophages indicate an indiscriminate, triggered response. This prompts a reconsideration of the underlying mechanisms.

p53 Protein expression in squamous cell carcinomas from sun-exposed and non-sun-exposed sites.

BACKGROUND: In sun-exposed nonmelanoma skin cancers, observation of specific p53 gene mutations implicate the role of UV radiation-induced mutations in the pathogenesis of these tumors. Immunohistochemical p53 protein overexpression and p53 gene mutation have been frequently considered related events. OBJECTIVE: We investigated the differences in p53 immunostaining in squamous cell carcinomas (SCCs) with varying degrees of differentiation, from both chronically sun-exposed and sun-protected sites of the skin. METHODS: Twenty-six SCCs (15 UV-related and 11 UV-unrelated) and five specimens of Bowen's disease (in situ SCC) from sun-exposed skin were examined by means of BP53-12-1 monoclonal antibody immunohistochemistry. RESULTS: p53 Immunoreactivity was observed in 66.7% of sun-exposed, 54.5% of non-sun-exposed invasive SCCs (Fisher's exact test, p = 0.689), and 80% of Bowen's disease specimens. In 50% of all samples, p53 positivity was more prominent in the proliferating periphery of the tumor with gradual loss of positivity as the cells differentiated. CONCLUSION: The reliability of p53 immunohistochemistry needs further molecular genetic studies.

Epithelioid sarcoma: a clinicopathologic and prognostic study of 26 cases.

Twenty-six cases of epithelioid sarcoma having a minimum of 5 years follow-up are presented. The patients ranged in age from 11 to 64 years; 18 were between 20 and 40 years of age. Males predominated (18:8). The most common tumor locations were the fingers (6 cases), the wrist (5 cases), and the hand (4 cases). All tumors were typical histologically, with medium-sized to large epithelioid and plump spindle cells, a predominantly nodular growth pattern, and intranodular collagen. Features seen in a minority of cases included hyalinized collagen, calcification, myxoid areas, and focal small cells. The major factor related to distant metastasis and death from tumor proved to be tumor size; all 7 patients with neoplasms > or = 5 cm died of tumor, and 6 had distant metastases, whereas only 2 of 10 patients with smaller tumors developed distant metastases and died (of patients with neoplasms of unknown size, 3 died of tumor and 2 of those along with 1 other had distant metastases). Five patients had regional lymph nodes involved (4 with tumors > or = 5 cm, 1 with tumor of unknown size), and all died. Local recurrence was primarily associated with treatment by excision alone (9 of 10 cases) rather than amputation (2 of 8 cases) or excision and radiation (2 of 8 cases); recurrences were often controlled by subsequent amputation. When tumor size and treatment were taken into account, histological variables including mitotic rate, tumor necrosis, and perineural invasion were not significantly related to recurrence, metastasis, or patient survival.

Sarcomatoid collecting duct carcinoma: a clinicopathologic and immunohistochemical study of five cases.

Sarcomatoid renal cell carcinoma is a well-known entity, but sarcomatoid collecting duct carcinoma has not been reported. We recently encountered five cases. The patients were men whose ages ranged from 59 to 82 years (mean age, 68 years). All presented with gross hematuria and three had abdominal fullness. Tumor size ranged from 6 to 9 cm in greatest dimension. The Fuhrman's nuclear grade of the carcinomatous components was 3 in three cases and 4 in two. The sarcomatoid areas were composed of pleomorphic spindle cells forming a malignant fibrous histiocytomatous pattern in four cases and a fibrosarcomatous pattern in one. The immunohistochemical findings in the carcinomatous and sarcomatoid components were identical. Wide-spectrum anti-cytokeratin cocktail, epithelial membrane antigen, and vimentin antibodies demonstrated immunoreactivity, while Leu-M1 did not react in all five cases. Three of the five tumors were positive for Ulex europaeus agglutinin I lectin. One sarcomatoid carcinoma reacted with monoclonal antibody to high molecular weight keratins, and all five tumors reacted with a monoclonal antibody to low molecular weight keratins. Two patients died at 5 months and 13 months after diagnosis, two are alive with metastatic disease at 1 and 14 months, and one is alive with no evidence of disease at 36 months.