Validation of epidermal AMBRA1 and loricrin (AMBLor) as a prognostic biomarker for nonulcerated American Joint Committee on Cancer stage I/II cutaneous melanoma.

BACKGROUND: Combined expression of the autophagy-regulatory protein AMBRA1 (activating molecule in Beclin1-regulated autophagy) and the terminal differentiation marker loricrin in the peritumoral epidermis of stage I melanomas can identify tumour subsets at low risk of -metastasis. OBJECTIVES: To validate the combined expression of peritumoral AMBRA1 and loricrin (AMBLor) as a prognostic biomarker able to identify both stage I and II melanomas at low risk of tumour recurrence. METHODS: Automated immunohistochemistry was used to analyse peritumoral AMBRA1 and loricrin expression in geographically distinct discovery (n = 540) and validation (n = 300) cohorts of nonulcerated American Joint Committee on Cancer (AJCC) stage I and II melanomas. AMBLor status was correlated with clinical outcomes in the discovery and validation cohorts separately and combined. RESULTS: Analysis of AMBLor in the discovery cohort revealed a recurrence-free survival (RFS) rate of 95.5% in the AMBLor low-risk group vs. 81.7% in the AMBLor at-risk group (multivariate log-rank, P < 0.001) and a negative predictive value (NPV) of 96.0%. In the validation cohort, AMBLor analysis revealed a RFS rate of 97.6% in the AMBLor low-risk group vs. 78.3% in the at-risk group (multivariate log-rank, P < 0.001) and a NPV of 97.6%. In a multivariate model considering AMBLor, Breslow thickness, age and sex, analysis of the combined discovery and validation cohorts showed that the estimated effect of AMBLor was statistically significant, with a hazard ratio of 3.469 (95% confidence interval 1.403-8.580, P = 0.007) and an overall NPV of 96.5%. CONCLUSIONS: These data provide further evidence validating AMBLor as a prognostic biomarker to identify nonulcerated AJCC stage I and II melanoma tumours at low risk of disease recurrence.

Mohs micrographic surgery and secondary intention healing of a plantar melanoma in-situ.

This report details an acral melanoma in-situ on theright plantar foot that was successfully treated withMohs micrographic surgery and secondary intentionwound healing.

Clinical stage of Merkel cell carcinoma and survival are not associated with Breslow thickness of biopsied tumor.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive malignancy that often presents on the skin with concurrent metastatic disease. OBJECTIVE: To determine whether Breslow thickness of biopsied MCC correlates with clinical disease stage. MATERIALS AND METHODS: We performed a retrospective review of clinical data and histopathology specimens from 34 individuals with MCC treated at the Roswell Park Cancer Institute for whom complete clinical information and histopathology specimens were available. RESULTS: There was no correlation between Breslow thickness of biopsied MCC on the head and neck or body and clinical stage of disease, progression-free survival, or overall survival. Hence, thin MCCs should not be taken to represent lesions with less-aggressive clinical behavior. CONCLUSION: Our findings validate the current practice of staging all newly diagnosed MCC, irrespective of size or Breslow thickness.

Can direct immunofluorescence testing still be accurate if performed on biopsy specimens after brief inadvertent immersion in formalin?

BACKGROUND: Direct immunofluorescence is useful in the diagnosis of autoimmune, vesiculobullous, and connective tissue diseases. Michel medium is typically indicated for transport, but clinicians may inadvertently place samples into formalin. OBJECTIVE: We set out to determine the amount of time that specimens can remain in 10% buffered formalin and still retain their diagnostic properties. METHODS: Biopsy samples were examined from cases with established diagnoses of bullous pemphigoid (n = 12), dermatitis herpetiformis (n = 6), and pemphigus vulgaris (n = 6) and exposed to formalin for time points ranging from 2 minutes to 4 hours. RESULTS: We found that immunoreactants were detectable in the majority of samples when subjected to 2 minutes of formalin exposure. Dermatitis herpetiformis and pemphigoid samples retained immunogenicity for 10 minutes, whereas pemphigus showed reduced immunogenicity for all samples studied. A nonimmunologic nuclear fluorochroming pattern was noted in some of the specimens after formalin immersion. LIMITATIONS: Sample size, only examining 3 disease processes, and samples already having been in Michel medium were the major limitations in the study. CONCLUSION: In direct immunofluorescence studies, formalin exposure to biopsy specimens causes two types of artifactual changes: (1) the shortest exposure (2 minutes) causes complete loss of diagnostic markers of pemphigus; and (2) prolonged exposure changes tissue to a form that allows fluorescein-labeled antibodies to give fluorochroming reactions of nuclei (which can be mistaken for in vivo antinuclear antibody reactions of lupus erythematosus). After time intervals of 10 minutes to 2 hours, direct immunofluorescence studies of proven cases of bullous pemphigoid and dermatitis herpetiformis retained variable levels of specific reactivity.

Furuncular myiasis: a case report.

Most clinicians associate myiasis with travel to a tropical location. We report a case of endemic myiasis due to Cuterebra species to remind clinicians that myiasis can occur throughout North America.

Nodular lymphangitis: Report of a case with presentation of a diagnostic paradigm.

A 54-year-old man with asthma, mitral valve prolapse, and a back injury developed erythematous nodules that progressed along the lymphatic drainage of his right arm. Skin biopsy revealed granulomatous inflammation with microabscess formation. Culture confirmed Mycobacterium marinum infection. The patient was treated with clarithromycin, ethambutol, rifampin, and topical silver sulfadiazine. Oral doxycycline hyclate was later added because of slow healing. Mycobacterium marinum is one of a group of infectious agents that can cause nodular lymphangitis. Sporotrichoid lesions most commonly develop after cutaneous inoculation with Sporothrix schenckii, Leishmania species, Nocardia species, and Mycobacterium marinum. A thorough clinical history and physical examination can narrow the differential diagnosis by eliciting information about the etiologic setting, incubation time, clinical appearance of the lesions, and presence or absence of systemic involvement for each of the causative organisms. Skin biopsy and microbiological tissue cultures are essential for diagnostic confirmation. The differential diagnosis and a suggested diagnostic paradigm will be reviewed.