Kathleen J. Smith

Topical imidazoquinoline therapy of cutaneous squamous cell carcinoma polarizes lymphoid and monocyte/macrophage populations to a Th1 and M1 cytokine pattern

Imidazoquinolines are topical immune response modifiers. Imiquimod (IMI), the first imidazoquinoline, is approved for the treatment of genital human papillomavirus disease and has shown success as a therapeutic agent for cutaneous premalignant and malignant tumours. To define the pattern of polarization of the local immune response to invasive cutaneous squamous cell carcinoma (SCC) we pretreated 10 SCCs that were >u20033u2003cm in diameter for 2u2003weeks with IMI. The tumours were treated on Monday, Wednesday and Friday and excised the next Monday. A battery of immunohistochemical markers was used to define the mononuclear cell populations in the diagnostic, and the excisional biopsy specimens. The total inflammatory infiltrate was increased after IMI therapy: the greatest increase was in the CD8 T cells with a marked relative decrease in the CD68 monocytic/macrophages; the majority of the CD8 T cells showed expression of cytotoxic granules, T cell‐restricted intracellular antigen (TIA) and granzyme B. The relative numbers of monocytes/macrophages were decreased after therapy with IMI with a decrease in CD68+, CD23+, and CD14+ cells and an increase in MAC‐397+, and factor XIIIa+ cells. The epidermal dendritic cells showed a >u200375% decrease in CD1a+ cells. The immunohistochemical marker profile after IMI therapy is consistent with that induced by a Th1 and M1 cytokine polarization pattern. This cytokine pattern is known to be more effective in defence against tumours as well as viral infections.

An unusual dematiaceous fungal infection of the skin caused by Fonsecaea pedrosoi: a case report and review of the literature

Background:u2002 A case of an unusual dematiaceous fungal infection of the skin in a 43‐year‐old man with diabetes mellitus treated with steroids for reactive airway disease is presented. He developed chromoblastomycosis in the left wrist and was treated with antifungals and multiple surgical excisions.

Cutaneous lesions showing giant yeast forms of Blastomyces dermatitidis

Background: The yeast forms of Blastomyces dermatitidis usually range from 8 to 15–20u2003µm in diameter. Larger yeast forms have previously been reported only twice in immunosuppressed patients. In both patients these large forms were seen within the lung.

Benign ectopic thyroid tissue in a cutaneous location: a case report and review

Background:u2002 For many years, lateral, aberrant thyroid tissue in adults was a term used almost exclusively for metastatic thyroid carcinoma. However, aberrant, benign ectopic thyroid tissue does occur, and it is most commonly found as a part of the evaluation of endocrine dysfunction. Rarely, aberrant, benign ectopic thyroid presents as a primary mass.

Histologic features seen in changing nevi after therapy with an 810 nm pulsed diode laser for hair removal in patients with dysplastic nevi

Abstract

Mucoepidermoid carcinoma arising within nevus sebaceus of Jadassohn

Background:u2002 Nevus sebaceus (NS) of Jadassohn is a common congenital lesion associated with numerous benign and malignant tumors. However, mucoepidermoid carcinoma (MEC) has not been described in association with NS.

Basaloid follicular hamartomas associated with autoimmune disease: a possible role for retinoids in therapy

A basaloid follicular hamartoma (BFH) may be localized or diffuse. It may also be congenital or acquired. Development of diffuse BFHs has been associated with autoimmune disease and with the development of diffuse alopecia. Two women with autoimmune diseases had diffuse alopecia develop. We present the histologic features of BFH seen in these 2 women using vertical and transverse sections, and the response of 1 patient to retinoid therapy. Histologic sections showed a hamartomatous proliferation of hair follicles involving the majority of their hairs. The hamartomatous follicles showed variable degrees of hair differentiation. One patient, treated with oral and then topical retinoids, showed a partial regrowth of scalp hair and some regression of the cutaneous nodules. Increased sonic hedgehog signaling pathways with increased Gli-1 transcription has been shown to be present in the spectrum of follicular hamartomatous changes seen in BFHs. This may explain the response of one patient to retinoid therapy, because retinoids decrease Gli-1 transcriptional activity.

Giant basal cell carcinoma associated with human papillomaviruses infection

Abstract:u2002 Different criteria have been used to define giant basal cell carcinoma (BCC). However, the majority of tumors of 10u2003cm or greater in diameter have a characteristic clinical and histopathologic presentation. As a group, these tumors often show metastatic spread as opposed to all other BCCs that rarely metastasize. We present an additional patient with a giant BCC greater than 100u2003cm2. This tumor had a characteristic location and infiltrative growth pattern. Unusual features of this tumor included a lack of expression of BCL‐2 with a greater proportion of cycling tumor cells expressing proliferation markers than conventional BCC, as well as expression of anogenital human papillomaviruses (HPV) subtypes with oncogenic potential. The association of HPV with BCCs has rarely been studied and may not be identical to HPV‐induced genital squamous cell carcinomas. However, the findings in this patient suggest that HPV may play a role in the development of some chronic giant BCCs.

Overview of Merkel cell carcinoma and recent advances in research – Editorial

The low incidence of Merkel cell carcinomas (MCCs) has hampered efforts to determine the prognosis as well as the best staging and treatment protocols of these aggressive neoplasms. Krasagakis and Tosca 1 review the cytogenetic changes which have been characterized in MCCs by karyotyping and comparative genomic hybridization (CGH), and they speculate on candidate oncogenes and tumor suppressor genes at these sites that may be involved in the pathogenesis of MCC. They specifically discuss the frequency of P53 mutations, and UVB-specific P53 mutations which have been found in MCC, as well as the frequency of deletion or other possible defects in the P53 family member P73. 1 Another recent study using multiplex-fluorescence in situ hybridization (M-FISH) has been performed with karyotyping and CGH comparing findings in both primary and metastatic MCC. 2 These additional studies have confirmed some previous findings and suggest that telomerase up-regulation, which is important for telomere extension for immortalization, may result from some of the cytogenetic defects. With continued accurate cytogenetic profiling of the chromosomal changes within primary, recurrent, nodal metastasis, and widespread metastatic MCC, new perspectives may be found in the search for candidate tumor suppressor genes or oncogenes that play a role not only in the development of MCC, but also in the progression of these tumors. Understanding the molecular basis of MCC development and progression could lead to more selective therapies for different stages of disease. The increased incidence of MCC in elderly individuals and in immunosuppressed patients, particularly in organ transplant recipients (OTRs), suggests that immune dysfunction may facilitate development and/or progression of MCC. 1

Overlap collagen vascular disease as a marker for development of primary biliary cirrhosis.

A 27‐year‐old black male presented with a 4 month history of polyarthritis and recurrent low grade fever. Laboratory findings revealed mild anemia, leukopenia, and thrombocytopenia (RBC 4.02 (4.70–6.10 m/UL), WBC 3.7 (4–11 K/UL), Platelets 130 (150–450 K/UL). Chemistries showed elevated total protein 9.7 (6.3–8.3) with normal albumin, alpha‐1, alpha‐2, and beta globulin levels and elevated gamma globulin levels 2.63 (0.64–1.17 G/DL), elevated aspartate aminotransferase (AST) 71 (17–49 U/L), alanine aminotransferase (ALT) 137 (7–56 U/L), lactate dehydrogenase (LDH) 629 (313–618 U/L) with normal creatinine phosphokinase, alkaline phosphatase, and bilrubin, elevated triglycerides 243 (35–160 MG/DL), decreased HDL 29 (34–65 MG/DL), elevated very low density lipoprotein (VLDL) 49 (0–40 MG/DL). Hepatitis screen was negative.