Jason B. Robbins

D2-40 lymphatic marker for detecting lymphatic invasion in thin to intermediate thickness melanomas: Association with sentinel lymph node status and prognostic value—A retrospective case study

BACKGROUND Sentinel lymph node (SLN) status is the greatest prognostic factor of morbidity in melanoma. D2-40 antibody specifically marks lymphatic endothelium and has been used for identifying lymphatic invasion (LI) in multiple cancers. OBJECTIVE We sought to determine the relationship between melanoma lymphatic invasion (as detected using D2-40 on primary melanoma biopsies/excisions) and the presence or absence of melanoma in subsequent SLN biopsy. METHODS We retrospectively evaluated LI using D2-40 on primary biopsies/excisions from patients with thin to intermediate thickness (Breslow thickness: ≤2.0 mm) melanomas, who underwent lymphatic mapping and SLN biopsy, and whose SLN status was known. Sixty-four cases met the criteria and were available for analysis. We analyzed patient age, patient sex, mitotic rate, ulceration, tumor depth, and D2-40 detected LI as predictors of SLN status. RESULTS Lymphatic invasion detection increased from 3.1% using hematoxylin and eosin only to 21.9% using D2-40. Twelve of 14 patients with D2-40 LI were SLN positive (positive predictive value, 85.7%). D2-40 LI was detected in the primary biopsy specimen of 12 of 18 patients with a positive SLN (sensitivity 66.7%). Of 50 patients without D2-40 LI, 44 were SLN negative (negative predictive value, 88.0%). Of 46 SLN-negative patients, 44 did not have D2-40 LI (specificity, 95.7%). LIMITATIONS Results are retrospective and limited to SLN biopsy performed at one institution. CONCLUSIONS On univariate and multivariate analysis, D2-40-detected LI was the most significant predictor of SLN status. D2-40 antibody staining to detect lymphatic invasion should be incorporated in routine melanoma biopsy evaluation.

Expression of activated Akt in benign nevi, Spitz nevi and melanomas.

Background:  Activated Akt expression (p‐Akt) is reportedly increased in many melanomas as compared with benign nevi. The purpose of this study was to evaluate and compare p‐Akt immunohistological staining in benign nevi, Spitz nevi and primary melanomas.

Contribution of beta-HPV infection and UV damage to rapid-onset cutaneous squamous cell carcinoma during BRAF-inhibition therapy

Purpose: BRAF-inhibition (BRAFi) therapy for advanced melanoma carries a high rate of secondary cutaneous squamous cell carcinoma (cSCC) and risk of other cancers. UV radiation and α-genus human papillomavirus (HPV) are highly associated with SCC, but a novel role for β-genus HPV is suspected in BRAFi-cSCC. Cutaneous β-HPV may act in concert with host and environmental factors in BRAFi-cSCC. Experimental Design: Primary BRAFi-cSCC tissue DNA isolated from patients receiving vemurafenib or dabrafenib from two cancer centers was analyzed for the presence of cutaneous oncogenic viruses and host genetic mutations. Diagnostic specimens underwent consensus dermatopathology review. Clinical parameters for UV exposure and disease course were statistically analyzed in conjunction with histopathology. Results: Twenty-nine patients contributed 69 BRAFi-cSCC lesions. BRAFi-cSCC had wart-like features (BRAFi-cSCC-WF) in 22% of specimens. During vemurafenib therapy, BRAFi-cSCC-WF arose 11.6 weeks more rapidly than conventional cSCC when controlled for gender and UV exposure (P value = 0.03). Among all BRAFi-cSCC, β-genus HPV-17, HPV-38, HPV-111 were most frequently isolated, and novel β-HPV genotypes were discovered (CTR, CRT-11, CRT-22). Sequencing revealed 63% of evaluated BRAFi-cSCCs harbored RAS mutations with PIK3CA, CKIT, ALK, and EGFR mutations also detected. Conclusions: We examined clinical, histopathologic, viral, and genetic parameters in BRAFi-cSCC demonstrating rapid onset; wart-like histomorphology; β-HPV-17, HPV-38, and HPV-111 infection; UV damage; and novel ALK and CKIT mutations. Discovered β-HPV genotypes expand the spectrum of tumor-associated viruses. These findings enhance our understanding of factors cooperating with BRAF inhibition that accelerate keratinocyte oncogenesis as well as broaden the knowledge base of multifactorial mediators of cancer in general. Clin Cancer Res; 21(11); 2624–34. ©2015 AACR.

Localized cutaneous argyria: two case reports and clinicopathologic review.

We report 2 cases of patients who presented with blue macules clinically suspicious for blue nevi. One patient had no documented history of trauma or silver exposure, and the other reported exposure to silver over 30 years ago. Microscopic examination revealed a dermal population of brown-black globules predominantly adhering to collagen fibers. In both cases, no melanocytic proliferation was identified by immunohistochemistry. Analysis of the skin biopsies with scanning electron microscopy and energy dispersive x-ray spectroscopy demonstrated the presence of silver and selenium. These findings were diagnostic of localized cutaneous argyria. Our case reports highlight the importance of including localized cutaneous argyria in the differential diagnosis of pigmented lesions.

Wound healing of 6.45-μm free electron laser skin incisions with heat-conducting templates

We have previously shown a reduction in lateral thermal damage with acute studies of skin incisions made in vitro using heat-conducting templates. Here we examined the wound-healing response to laser incisions with heat-conducting templates and explored the use of an optically transparent template with the free electron laser (FEL) at 6.45 microm. First we evaluated the effects of a sapphire heat-conducting template on the lateral thermal damage of FEL incisions using in vitro human skin samples. Next we compared wound tensile strength and histological scoring of the healing of incisions created on the dorsal pelts of live rats with the FEL utilizing metal and sapphire heat-conducting templates and scalpel incisions. The animals were euthanized and the wounds were analyzed at postoperative days 7, 14, and 21. The depth and lateral thermal damage of FEL incisions on in vitro human skin were significantly reduced with the sapphire heat-conducting template. Nonstatistically significant differences in wound tensile strengths and histological scoring of wound healing were noted at days 7 and 14. By day 21, all of the incisions appeared similar. When the data from days 7 and 14 were combined, statistically significant differences were found for each of the templates (except the histological evaluation with the aluminum template) and the scalpel compared with laser incisions made without using a template. The use of metal or sapphire heat-conducting templates reduced the wound-healing delay of laser incisions seen at postoperative days 7 and 14.

Cutaneous Focal Mucinosis Causing Follicular Induction of the Epidermis

Cutaneous focal mucinosis has been rarely reported in association with follicular induction of the epidermis. We present 2 cases of focal mucinosis with follicular induction and describe the histopathologic findings to create awareness of this association and to prevent confusion with other diagnoses such as dermatofibroma with follicular induction or superficial basal cell carcinoma.

Nasal tumor in a Peruvian man.

DISCUSSION The correct diagnosis is rhinoscleroma. Rhinoscleroma is a progressive granulomatous infection principally involving the upper respiratory tract caused by the gram-negative bacterium Klebseilla rhinoscleromatis. Terra cotta head masks from the Mayan culture (300 to 600 AD) have demonstrated nasal deformities and represent the earliest known evidence of this condition. The nasal cavity is usually involved (95% to 100%), but the nasopharynx, larynx, trachea, and bronchi may also be affected. Concomitant skin lesions arise near involved mucosa. Gaafar et al described 4 cases in which the skin lesions involving the upper cutaneous lip, dorsum of the nose, or nasolacrimal sac area were direct extensions from intranasal lesions. Rhinoscleroma is most prevalent in low socioeconomic environments of Central and South America, tropical Africa, India, southeast Asia, Central Europe, and the Middle East. It is rare in the United States with most cases being imported from endemic areas. Clinically, rhinosceleroma is divided into 3 stages. In the initial catarrhal stage, patients present with a nonspecific rhinitis and a foul-smelling purulent discharge. In the second or granulomatous stage, bluish-red, rubbery granulomas develop on the nasal mucosa. Patients often complain of epistaxis and nasal deformity. Other clinical findings depend on the areas affected. Anosmia, hoarseness, or dysphonia with laryngeal involvement, and various degrees of airway obstruction may occur. The characteristic histopathologic features are present in this stage and consist of intense granulomatous inflammation with abundant plasma cells, Russell bodies, lymphocytes, and large vacuolated histiocytes (Mikulicz cells) containing rod-shaped bacteria (Figs. 1 and 2). The final or sclerotic stage is characterized by extensive fibrosis that may lead to respiratory tract stenosis and deformity. The differential diagnosis includes tuberculosis, leprosy, syphilis, rhinosporidiosis, mucocutaneous leishmaniasis, actinomycosis, histoplasmosis, blastomycosis, paracoccidioidomycosis, advanced yaws, Wegener’s granulomatosis, lymphomas, and carcinomas. The diagnosis is made by clinical correlation and histopathology. A bacterial culture on blood or MacConkey agar is diagnostic, but positive in only 50% of cases. Therapy involves prolonged (months to years) antimicrobial therapy with tetracycline or the fluoroquinolones. Other agents used with some success include rifampin, doxycycline, trimethoprim-sulfamethoxazole, and clofazimine. Surgical debridement is reserved for patients with airway compromise and tissue deformity.

Mycosis fungoides involving an acrochordon: a case report

We present the case of a 77‐year‐old male undergoing treatment for mycosis fungoides (MF) who presented for removal of an acrochordon on his mid back. Histopathologic examination of the acrochordon revealed a dense, band‐like lymphocytic inflammatory infiltrate in the dermis with epidermotropism of single lymphocytes and small nests of lymphocytes into the lower epidermis. Immunohistochemical staining characterized the dermal and epidermal lymphocytic population as CD3‐positive T lymphocytes with a predominance of CD4‐positive over CD8‐positive lymphocytes. These findings were consistent with the patients known MF and molecular identification of a clonal T‐cell receptor gene rearrangement further supported the diagnosis. Our unusual case reports MF involving an acrochordon and provides evidence to support the importance of submitting acrochordons for histopathologic examination.