Christine J. Ko

Keratoacanthoma: Facts and controversies

The keratoacanthoma and its variants are clinically and histologically heterogenous. Some consider the keratoacanthoma to be benign, whereas others classify it as a subtype of squamous cell carcinoma. The keratoacanthoma is generally treated rather than observed for spontaneous resolution. This hampers evaluation of the true natural history of lesions diagnosed as keratoacanthoma. In addition, studies have not found a reliable marker to differentiate keratoacanthoma from squamous cell carcinoma. It currently remains unclear how the keratoacanthoma relates to squamous cell carcinoma, and continued investigation is necessary.

Spontaneous tumour regression in keratoacanthomas is driven by Wnt/retinoic acid signalling cross-talk

A fundamental goal in cancer biology is to identify the cells and signalling pathways that are keys to induce tumour regression. Here we use a spontaneously self-regressing tumour, cutaneous keratoacanthoma (KAs), to identify physiological mechanisms that drive tumour regression. By using a mouse model system that recapitulates the behaviour of human KAs, we show that self-regressing tumours shift their balance to a differentiation programme during regression. Furthermore, we demonstrate that developmental programs utilized for skin hair follicle regeneration, such as Wnt, are hijacked to sustain tumour growth and that the retinoic acid (RA) signalling pathway promotes tumour regression by inhibiting Wnt signalling. Finally, we find that RA signalling can induce regression of malignant tumours that do not normally spontaneously regress, such as squamous cell carcinomas. These findings provide new insights into the physiological mechanisms of tumour regression and suggest therapeutic strategies to induce tumour regression.

Langerhans cells in squamous cell carcinoma vs. pseudoepitheliomatous hyperplasia of the skin

Background:  In clinical and histopathological practice, it is sometimes difficult to distinguish pseudoepitheliomatous hyperplasia (PEH) from squamous cell carcinoma (SCC) of the skin. Several studies have shown a low density of Langerhans cells in SCC of the skin, and recent research on cervical SCCs has suggested that the decreased density of dendritic cells is secondary to low E‐cadherin expression. SCCs of the head and neck similarly have decreased E‐cadherin expression, but E‐cadherin expression is preserved in PEH. We hypothesized that PEH of the skin would have an increased number of Langerhans cells compared with SCC.

Actinic keratosis: Facts and controversies

Actinic keratoses are common lesions that are generally clinically diagnosed. Although currently most actinic keratoses are treated, whether this is truly necessary is debated. Treatment of all actinic keratoses is advocated because preliminary evidence indicates that actinic keratoses may progress to squamous cell carcinomas. Some also consider actinic keratoses equivalent to squamous cell carcinoma.

Somatic Activating RAS Mutations Cause Vascular Tumors Including Pyogenic Granuloma

Young H. Lim1,2,5, Stephanie R. Douglas3, Christine J. Ko1,2, Richard J. Antaya1,4, Jennifer M. McNiff1,2, Jing Zhou1,2,5, Yale Center for Genome Analysis, Keith A. Choate1,2,5,*, and Deepak Narayan3,* 1Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut, USA 2Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA 3Section of Plastic Surgery, Department of Surgery, Yale University School of Medicine, New Haven, Connecticut, USA

Calcospherules associated with juvenile hyaline fibromatosis.

&NA; Juvenile hyaline fibromatosis is a rare autosomal recessive genodermatosis that manifests with 1 to 5 cm skin tumors, gingival hyperplasia, osteolytic bone lesions, and joint contractures. The skin tumors are most often located on the head and periarticular extremities. A case of juvenile hyaline fibromatosis with typical skin tumors that on biopsy exhibited basophilic calcospherules is presented. Although noted in a single case, these structures may be a novel, yet helpful, diagnostic marker.

Neutrophilic Dermatosis After Azathioprine Exposure

IMPORTANCE Azathioprine hypersensitivity syndrome can present clinically and histopathologically like Sweet syndrome. Shared clinical features include fever, constitutional symptoms, prompt response to systemic corticosteroid therapy, neutrophilia, and abrupt onset of erythematous cutaneous lesions. Histologically, both azathioprine hypersensitivity syndrome and Sweet syndrome are rich in neutrophils. OBSERVATIONS An 81-year-old woman with Crohn disease presented with fever and an acute eruption of plaques on her extremities within 2 weeks of starting treatment with azathioprine. Laboratory evaluation was notable for leukocytosis and neutrophilia. Skin biopsy of an erythematous plaque on the thigh demonstrated a suppurative folliculitis. Azathioprine treatment was discontinued resulting in resolution of the clinical lesions within 5 days. Our case was compared with 18 cases with similar clinical features. CONCLUSIONS AND RELEVANCE We report a case of azathioprine hypersensitivity syndrome and review the literature on azathioprine-induced eruptions with features of Sweet syndrome. Our patients distribution of lesions on the extremities and the finding of suppurative folliculitis on histopathology were not classical for Sweet syndrome. Azathioprine hypersensitivity syndrome seems to be a neutrophil-driven dermatosis; therefore, many overlapping features with Sweet syndrome are not surprising. Due to the potential for anaphylaxis with azathioprine rechallenge, a better term for a Sweetlike presentation in the setting of azathioprine administration is azathioprine hypersensitivity syndrome.

Muir-Torre syndrome: Facts and controversies.

The cutaneous presentation of a tumor sometimes has implications for a patient and his or her family, and Muir-Torre syndrome is an example of this. Because a single skin lesion can have broad consequences, it is important for clinicians to be aware of Muir-Torre syndrome. The definition, potential clues, the role of ancillary testing (microsatellite, immunohistochemical, and genetic), and screening recommendations are reviewed.

Squamous cell carcinomas with single cell infiltration: a potential diagnostic pitfall and the utility of MNF116 and p63.

Numerous variants of squamous cell carcinoma (SCC) have been described. We recently encountered four examples of SCC composed primarily of single, atypical cells that were cytokeratin (CK) MNF116‐positive and p63‐positive. One case was particularly difficult to diagnose as the single cells were obscured by a dense inflammatory infiltrate. We have also noted similar single cell infiltration toward the periphery of four additional cases of more typical SCC. These foci resemble the single tumor cells that may infiltrate at the borders of spindle cell and desmoplastic SCCs. CK MNF116 and p63 were useful in identifying each of these neoplasms. This single – cell pattern of SCC can easily be misdiagnosed, and CK MNF116 and/or p63 are diagnostically helpful in recognizing it.

Fibrillar IgA deposition in dermatitis herpetiformis – an underreported pattern with potential clinical significance

Dermatitis herpetiformis has characteristic clinical and histopathologic findings. A fibrillar pattern of IgA deposition on direct immunofluorescence in dermatitis herpetiformis is underreported. Here, we describe three patients with the fibrillar pattern of IgA deposition on direct immunofluorescence examination that initially misled diagnosis in one of the three. Interestingly, two of the three patients lacked anti‐transglutaminase and anti‐endomysial antibodies but had a clinical course typical of dermatitis herpetiformis. Dermatitis herpetiformis may have a fibrillar rather than granular pattern of IgA deposition on direct immunofluorescent microscopy, and patients with this pattern of immunoglobulin deposition may lack circulating autoantibodies.