Refractory aggressive keratoacanthoma centrifugum marginatum of the scalp controlled with the epidermal growth factor receptor inhibitor erlotinib.

Keratoacanthomas are squamous cell neoplasms known to be abundant in epidermal growth factor receptors (EGFRs). Erlotinib (Tarceva(®); Roche) is a low molecular weight oral quinazoline compound that binds to the intracellular EGFR tyrosine kinase domain and inhibits receptor phosphorylation and downstream signalling. We report a case of refractory, locally aggressive keratoacathoma centrifugum marginatum of the scalp having strong EGFR expression and demonstrating excellent response to erlotinib.

Laryngeal squamous cell carcinoma with infradiaphragmatic presentation of skin metastases.

Distant metastases in squamous cell carcinoma of the larynx have an incidence of 6.5-7.2%, and most commonly involve the lungs, liver and bone. Metastases to the skin are exceedingly rare, with only 30 cases reported in the literature. Skin metastases may represent the first clinical evidence of impending locoregional recurrence, suggest distant metastatic spread, or rarely, be the first sign of 'silent' laryngeal tumour. They are usually considered a poor prognostic sign and most often affect the supradiaphragmatic area, i.e. the head, neck, thorax or upper extremities. Infradiaphragmatic presentation of metastatic laryngeal squamous cell carcinoma is exceptional, with only four cases reported in the literature. Here we present another.

Tufted hair folliculitis: a pattern of scarring alopecia?

We present a patient with pemphigus vulgaris who, over the years, experienced the development of tufted hair folliculitis as a result of scalp involvement. Multiple hairs emerged from widely dilated follicular ostia surrounded by indurated, scarred skin. Histopathologic findings were typical for tufted hair folliculitis. We believe that because a specific host response to scalp injury might be crucial to the development of this rare disorder, it should be regarded as a type of scarring alopecia.

Desmoglein in multiple self-healing squamous epithelioma of Ferguson-Smith--comparison of staining patterns with actinic keratoacanthoma and squamous cell carcinoma of the skin.

BACKGROUND: Multiple self-healing squamous cell epithelioma of the skin (MSSE) is the most common variant of multiple keratoacanthoma. Although the morphology of the lesions in MSSE is similar to classical actinic keratoacanthoma (KA), several distinctive features in clinical presentation and histology have been emphasized. Desmosomes have been shown to be downregulated in certain types of carcinoma. Desmogleins (Dsg) are transmembrane desmosomal glycoproteins that exist as three isoforms. Dsg markers have been found to be reduced or absent in squamous cell carcinoma (SCC) but preserved in KA. OBJECTIVE: This study was designed to determine the pattern of Dsg staining in MSSE. METHODS: Eight tumors from two female patients with MSSE were stained with the antidesmoglein monoclonal antibody 32-2B, which recognizes Dsgl and Dsg3. RESULTS: All eight tumors showed uniform pericellular Dsg staining throughout the nonkeratinized layers of the neoplastic epithelium. This pattern is entirely similar to that observed in actinic KA, normal epidermis or follicular epithelium. CONCLUSION: Despite the differences, uniform preservation of Dsg seems to be the invariable feature of both MSSE and KA. Further studies are necessary to evaluate this antibody in routine dermatopathology of MSSE and SCC.

Immunohistochemical staining for desmogleins 1 and 2 in keratinocytic neoplasms with squamous phenotype: actinic keratosis, keratoacanthoma and squamous cell carcinoma of the skin.

Desmosomes are intercellular junctions that have been shown to be down-regulated in certain types of carcinoma and that may play a role in suppression of invasion and metastasis. This paper describes an immunohistochemical study of three types of epidermal neoplasms with monoclonal antibody to desmoglein in order to determine how desmosomal staining correlates with the clinical, biological and histopathological features of these neoplasms. Actinic keratosis (AK) is the most common keratinocytic premalignant neoplasm that was reported to have a 10-20% rate of malignant transformation into squamous cell carcinoma (SCC). Keratoacanthoma (KA) is a benign neoplasm that involutes spontaneously after a few months of rapid growth. SCC is a malignant tumour capable of metastasis. Electron microscope studies of KA and SCC showed significantly reduced staining for desmosomes in SCC but not in KA. We have examined staining for desmoglein using the monoclonal antibody 33-3D, a mouse IgM monoclonal antibody, that recognizes the cytoplasmic domains of desmoglein (Dsg)1 and Dsg2 on frozen sections. Immunohistochemical staining of normal skin with this antibody revealed strong pericellular localization of the antigen, outlining the cell membranes of the keratinocytes. A series of 30 AKs, 12 KAs and 24 SCCs was stained immunohistochemically with 33-3D monoclonal antibody. All examined KAs showed extensive pericellular staining for Dsg. By contrast, juxtanuclear staining for Dsg was noted in 12 SCCs, and completely negative staining in seven SCCs. The five remaining SCCs showed focal pericellular staining for the Dsg marker. The most common finding in AK was focal pericellular staining for Dsg, with complete absence of staining in dysplastic areas (25 cases). In five cases negative pericellular staining in dysplastic areas was associated with juxtanuclear accumulation of the Dsg marker. A strong negative correlation between Dsg staining and degree of dysplasia was obtained. The Dsg pattern in KA is similar to normal epidermis and shows a clear difference between KA and SCC. AK has a limited loss of Dsg expression in a SCC-like pattern that is congruent with its premalignant nature. As the stain works on frozen tissue, it may be helpful for rapid differentiation in selected cases in cutaneous oncology and Mohs micrographic surgery. This antibody may also have great potential for the detection of the effects of chemopreventive agents in skin cancer.

Microscopically controlled surgical excision combined with ultrapulse CO2 vaporization in the management of a patient with the nevoid basal cell carcinoma syndrome.

Nevoid basal cell carcinoma syndrome is an autosomal dominant condition characterized by multiple basal cell carcinomas, skeletal abnormalities and sometimes mental retardation. The large number of tumors, which are often disfiguring, presents extreme difficulties in the treatment of these patients. Microscopically controlled excision, compared to other modalities (radiation therapy, photodynamic therapy, intralesional interferon alpha-2b) offers the highest cure rate. However, because of the large size and involvement of wide areas of the skin, this approach is sometimes impractical. The ultrapulse CO2 laser with high energy and short pulses achieves char-free ablation of the tumors, bloodless surgical field, minimal nonspecific thermal damage, rapid healing and diminished postoperative pain. Also, a number of lesions can be removed in a single session. We present a 48-year-old man with a 6.5 x 4.5 cm large basal cell carcinoma involving the anterior abdomen and navel area. The central thick portion of the tumor was resected by microscopically controlled excision with 3 stages, and wide thinner peripheral crescentic plaque vaporized with ultrapulse CO2 laser. The laser settings were 300 mJ energy/pulse and 100 W average power, which corresponds to the fluence of 7.5 J/cm2. Computerized pattern generator (ultrascan handpiece) was adjusted to patterns of 3 (circle) and 1 (square) with sizes varying from 5 to 7, and density of 9 (60% overlapping). The tumor was vaporized with 6 passes, all the way to deep reticular dermis. A fifteen month-follow up disclosed no recurrent disease. Subsequent biopsies revealed only a scar with postinflammatory hyperpigmentation. Our experience indicates that combined treatment with microscopically controlled excision and ultrapulse CO2 laser ablation is a suitable modality for the large tumor plaques involving concave and convex areas of the skin respectively. Microscopically controlled excision of thicker, concave portions of basal cell carcinoma plaques, where CO2 laser surgery is less feasible, presents an effective addition that renders this combined modality a successful method for the treatment of nevoid basal cell carcinoma syndrome.

The use of antidesmoglein stains in Mohs micrographic surgery. A potential aid for the differentiation of basal cell carcinoma from horizontal sections of the hair follicle and folliculocentric basaloid proliferation.

BACKGROUND: Histopathologic differentiation between benign and malignant tissue is of utmost importance for the Mohs surgeon. Folliculocentric basaloid proliferation (FBP) shares many histologic features with basal cell carcinoma (BCC). It is most commonly associated with tumors of areas with abundant hair follicles such as nasal and perinasal skin. Residual BCC incorrectly identified as a horizontally sectioned hair follicle undoubtedly increases the risk of tumor recurrence. Excision of additional layers of normal tissue to remove "funny looking follicles" may have profound impacts on tissue conservation, preservation of function, and cosmesis. Electron microscope studies of BCC revealed a significant reduction of desmosomes compared with normal basal cells and hair follicle keratinocytes. OBJECTIVE: This study has assessed the potential of rapid staining with monoclonal antidesmoglein antibody (33-3D) to discriminate between BCC, horizontally sectioned hair follicles, and FBP. METHODS: A rapid immunoperoxidase technique with 33-3D antidesmoglein antibody was performed on Mohs frozen sections. We selected 18 patients with BCC of nasal and perinasal locations where histologic discrimination between residual tumor and tumor-free margins with FBP or horizontally sectioned hair follicle was equivocal. RESULTS: Fourteen sections disclosed the preservation of desmoglein marker delineating the cell membranes ("perimembranous" pattern) consistent with normal hair follicles. The sections were identified as tumor-free and no additional stages were performed. The remaining four sections revealed absent perimembranous pattern but presence of diffuse cytoplasmic staining. These were diagnosed as positive for residual BCC requiring the excision of another layer of tissue to obtain tumor-free margins. A follow-up period ranging from 6 to 24 months revealed no instance of recurrent disease. CONCLUSION: Rapid detection of desmoglein with 33-3D antibody is a promising tool for discrimination between residual BCC and FBP or horizontally sectioned hair follicles. It may enhance the sensitivity of Mohs surgery by disclosing the hidden foci of BCC, thus preventing tumor recurrence and unnecessary excision of normal tissue.

Multiple acral syringomata with uniform involvement of the hands and feet.

We present a case of a 43-year-old black woman with multiple syringomata located on the dorsa of the hands and feet. Although syringoma is a common adnexal tumor, acral presentation is very rare. Symmetrical involvement of the distal lower extremities has not been reported previously. This interesting clinical presentation should be included in the differential diagnosis of a papular eruption of the hands and feet.

Ectrodactyly, soft-tissue syndactyly, and nodulocystic acne: coincidence or association?

We report severe nodulocystic acne in a 21-year-old man associated with ectrodactyly of the right foot and soft-tissue syndactyly of the third and fourth left fingers, and the first to fourth left toes. His acne was resistant to conventional topical (clindamycin phosphate, erythromycin, tretinoin, peeling agents) and systemic (tetracycline, erythromycin) antiacne medications. Moderate improvement was achieved with systemic isotretinoin. Apart from presenting this case, we imply the disparity of the clinical characteristics of our case and those of Apert syndrome, a rare congenital condition with craniofacial anomalies, symmetric syndactyly of the digits, and acneiform eruption. We discuss the possible explanation for the association of acne lesions and bone deformities based on recent reports of mutations of fibroblast growth factor receptor 2 in the great majority of patients with this syndrome, as well as current experimental data on the involvement of the keratinocyte growth factor in the process of hair follicle growth, development, and differentiation.

Differential expression of desmosomal glycoproteins in keratoacanthoma and squamous cell carcinoma of the skin: an immunohistochemical aid to diagnosis.

The distinction between keratoacanthoma and squamous cell carcinoma is a common dermatopathological dilemma. Although the mainstay of the diagnosis is still clinico-pathological correlation, many dermatopathologists now include keratoacanthomas in the spectrum of squamous cell carcinomas. Recent reports, however, have pointed out that keratoacanthoma is "deficient squamous cell carcinoma" since it loses the expression of bcl-2 antigen, consistent with initiation of apoptosis, i.e. its involution. Electron microscope studies performed in keratoacanthomas and squamous cell carcinomas also revealed significantly reduced desmosomes in squamous cell carcinoma, but not in keratoacanthoma. A series of 38 keratoacanthomas and 62 squamous cell carcinomas of the skin (28 well-differentiated, 21 moderately differentiated and 13 poorly differentiated) were stained immunohistochemically with the monoclonal antibody 32-2B to desmosomal glycoproteins desmoglein 1 and desmoglein 3. Thirty-five keratoacanthomas showed extensive pericellular desmoglein expression. Three keratoacanthomas and 20 squamous cell carcinomas (19 well-differentiated, 1 moderately differentiated) showed focal staining, and in 11 squamous cell carcinomas (2 moderately differentiated, 9 poorly differentiated) the staining was negative. The remaining 31 squamous cell carcinomas (9 well differentiated, 18 moderately differentiated, 4 poorly differentiated) showed juxtanuclear staining. None of the squamous cell carcinomas exhibited the extensive pericellular pattern found in keratoacanthomas. Assessment of staining intensity, by 3 independent examiners, revealed a strong negative correlation between desmoglein expression and degree of dysplasia in the squamous cell carcinomas (p < 0.01). This antibody therefore clearly distinguishes these tumours and may be of value in the differential diagnosis of keratoacanthoma and squamous cell carcinomas in routine histopathology.

Pseudoepitheliomatous, keratotic and micaceous balanitis. Case report and review of the literature.

A case of pseudoepitheliomatous, keratotic and micaceous balanitis (PEKMB) in a 64-year old man is presented. The patient presented with the 2-year history of a slowly enlarging, hyperkeratotic plaque on his glans penis that was compatible with a clinical diagnosis of PEKMB. The lesion has been treated successfully with tropical 5-fluorouracil cream, with no evidence of recurrence at 2-year follow-up. Histological examination revealed acanthosis, hyperkeratosis, and pseudoepitheliomatous hyperplasia with no cytological atypia. This rare penile condition was considered pseudomalignant, premalignant, or as a low-grade squamous malignancy. Apart from this patient we comprehensively review previously reported cases, and discuss a possible concept on etiology, diagnosis and treatment of this entity.