Changes in sebum levels and the development of acneiform rash in patients with non-small cell lung cancer after treatment with EGFR inhibitors.

BACKGROUND: It has recently been shown that patients treated with epidermal growth factor receptor (EGFR) inhibitors often develop various cutaneous adverse events. While the pathogenesis underlying these events remains unclear, the relationship between skin toxicity induced by EGFR inhibitors and the sebaceous glands that express EGFR has been previously reported. OBJECTIVES: The primary aim of this study was to determine the relationship between cutaneous sebum levels and acneiform rash, a typical skin toxicity of EGFR inhibitors, by measuring the sebum levels before and after EGFR inhibitor treatment. METHODS: Eight patients diagnosed with non-small cell lung cancer (NSCLC) (three men and five women with an average age of 69.3 years) who were initiated on treatment with EGFR inhibitors (either gefitinib [Iressa(®)] or erlotinib [Tarceva(®)]) were enrolled. Using a Sebumeter(®), sebum levels in the face, chest, and back of each patient were measured before and after EGFR inhibitor treatment. The development of acneiform rash in each skin region was also assessed. RESULTS: Changes in sebum level along with the development of an acneiform rash were observed after patients were started on EGFR inhibitor treatment. Patients who developed an EGFR inhibitor-induced acneiform rash tended to have higher pretreatment sebum levels (baseline) than did patients who did not experience an acneiform rash. At each time point measurement, sebum levels were found to be significantly higher in patients who had developed an acneiform rash at that time. Patients who developed rash during treatment showed greater differences in sebum level compared with pretreatment baseline. CONCLUSION: Patients who had increased levels of sebum or whose sebum levels showed greater change from pretreatment baseline developed an acneiform rash, suggesting that sebaceous gland activity may be involved in the mechanism underlying the development of acneiform rash, in patients treated with EGFR inhibitors.

Four cases of successfully treated chronic expanding soft tissue hematoma.

Chronic expanding hematoma (CEH) is a rare, slow-developing disease that occurs months to years after trauma or surgery. Most CEH in soft tissue occurs in the thigh or upper extremities and can occur with or without an inducible cause. Ninety-one cases of CEH in soft tissue have been reported previously in the Japanese and English literature but its occurrence on the sole has not been reported. Here, we report four cases of successfully treated CEH, including a case occurring on the sole, and provide a review of the literature.

Phase II study of i.v. interferon-gamma in Japanese patients with mycosis fungoides.

A multisite, open-label, non-randomized, single-arm phase II study was conducted to evaluate the efficacy and safety profiles of interferon-γ in Japanese patients diagnosed with stage IA-IIIA mycosis fungoides (MF). Interferon-γ was administrated i.v. to 15 patients at a dose of 2 million Japan reference units once daily over 5 days a week for the first 4 weeks, followed by subsequent intermittent injection. The primary efficacy end-point was the overall skin response during the study as assessed according to the evaluation criteria for chemotherapeutics for malignant skin carcinomas. Of the 15 patients, 11 (73.3%) achieved the objective response. Of the other four patients, three remained on treatment during study with stable disease and one showed disease progression. The median duration of stable disease was not reached but was 170 days or more (range, 29 to ≥253 days). As assessed according to the modified severity weighted assessment tool, nine patients (60.0%) achieved the objective response. The most common drug-related adverse event (AE) was influenza-like illness occurring in all patients enrolled, which did not lead to discontinuation of the study. Two serious AE were reported in two patients: aggravation of MF and aggravation of cataract, neither of which was considered directly related to the study drug. The patient with aggravation of MF died 50 days after the initiation of the study treatment. Another patient was withdrawn from the study due to drug-related cough, which disappeared after discontinuation of the drug. Overall, interferon-γ was effective and well-tolerated in Japanese patients with MF.

Aberrant expression of S100A6 and matrix metalloproteinase 9, but not S100A2, S100A4, and S100A7, is associated with epidermal carcinogenesis.

BACKGROUND: S100 proteins belong to a family of calcium-binding proteins that regulate cell proliferation and differentiation. Despite our growing knowledge about the biology of S100 proteins in some human cancers, little is known about the expression of S100 family members in epidermal tumors and their clinical significance. OBJECTIVE: To determine the expression of S100A2, S100A4, S100A6, S100A7, as well as matrix metalloproteinases 9 (MMP9) in a spectrum of epidermal tumors with benign and malignant characteristics. METHODS: Immunohistological staining was performed for S100A2, S100A4, S100A6, S100A7, and MMP9 in 101 cases of various types of epidermal tumors, viz., squamous cell carcinoma (SCC), Bowen's disease (BD), actinic keratosis (AK), basal cell carcinoma (BCC), keratoacanthoma (KA), and seborrheic keratosis (SK). Thirteen specimens of normal skin (NS) served as control. RESULTS: S100A2, S100A6, and S100A7 positive immunostaining was variably observed in different epidermal tumors. S100A4 staining was not observed in any epidermal tumors, but was clearly visible in dendritic cells. MMP9 immunostaining was positive only in 22/26 (84.62%) of SCC and 2/15 (13.33%) of BD cases. Expression of S100A2, S100A6, and S100A7 was increased in tumor cells compared to NS. However, only S100A6 expression was significantly associated with malignant transformation of epidermal tumors. Moreover, S100A6 expression was correlated with MMP9 expression in metastatic SCC. CONCLUSIONS: Epidermal tumors show increased expression of S100A2 and S100A7 proteins. S100A4 may be a useful and distinct marker for epidermal dendritic cells. Expression of S100A6 and MMP9 in combination is associated with the development of SCC.

Antiphospholipid syndrome complicated by unilateral pleural effusion.

Antiphospholipid syndrome (APS) with pleural effusion is extremely rare. A 75-year-old man was admitted to our hospital for spreading erythema on his trunk and extremities, as well as dyspnea. One year before admission, he had visited us with a 1-year history of erythema and purpura on his legs and occasional fever. Given the diagnosis of APS, we initiated a combination therapy of aspirin and warfarin, but the skin lesions had gradually worsened. A biopsy specimen revealed marked thrombosis in the dermal and subcutaneous small vessels. In addition, chest X-ray and computed tomography demonstrated a large pleural effusion in the left lung. He underwent repeated drainage of the pleural effusion but the effusion recurred. We added oral prednisolone 30 mg daily to his prior anticoagulant therapy. The skin lesions and pleural effusion rapidly improved and disappeared without any complication. Corticosteroids might be a choice of treatment for intractable pleural effusion in APS patients.

Levels of the EMT-related protein Snail/Slug are not correlated with p53/p63 in cutaneous squamous cell carcinoma.

BACKGROUND: The contribution of the E-cadherin transcriptional repressors Snail and Slug to invasion and metastasis has strengthened the evidence for the importance of epithelial-mesenchymal transition (EMT) in carcinoma progression. However, to the best of our knowledge, no study has described the immunohistochemical staining of the EMT-related proteins Snail/Slug in skin tumors and the correlation between Snail/Slug and tumor suppressor p53/p63. METHODS: We performed immunohistological staining of Snail, Slug, E-cadherin, p53 and p63 in 20 archived specimens each of seborrheic keratosis (SK), actinic keratosis (AK) and squamous cell carcinoma in situ (SCCIS), and 53 specimens of cutaneous squamous cell carcinomas (SCC). Fifteen normal skin (NS) specimens served as controls. RESULTS: Significant negative correlations were observed between Snail and E-cadherin expression and between Slug and E-cadherin expression (Snail: R(2) = 0.5432, p < 0.01; Slug: R(2) = 0.4666, p < 0.01). CONCLUSIONS: The staining intensities of Snail and Slug are associated with decreased E-cadherin staining in SCC and this may promote EMT. However, the staining intensities of p53 and p63 are not significantly correlated with the loss of E-cadherin.

Cutaneous sarcoidosis clinically mimicking necrobiosis lipoidica in a patient with systemic sarcoidosis.

A 70-year-old woman with an 8-year history of systemic sarcoidosis developed round, red-brown eruptions, with central atrophic lesions on her lower legs. The features of the biopsy specimen resembled those of necrobiosis lipoidica (NL), but although necrobiosis was present there were well-formed non-necrotizing granulomas in the dermis. The histological diagnosis was cutaneous sarcoidosis. Systemic sarcoidosis presenting with NL has rarely been reported. The histological features of cutaneous sarcoidosis sometimes mimic those of other granulomatous diseases, including NL and granuloma annulare, which are difficult to distinguish. We discuss the novel association between sarcoidosis and other granulomatous diseases.

Prediction of additional lymph node positivity and clinical outcome of micrometastases in sentinel lymph nodes in cutaneous melanoma: a multi-institutional study of 450 patients in Japan.

Various microscopic classifications of metastatic sentinel lymph nodes (SLN) have been reported along with predictors of additional lymph node positivity and their correlations with the prognosis. The purpose of this study was to re-evaluate these classifications in the Japanese population. We selected the following three classifications, based on the procedural simplicity of the measurements: maximum diameter (maximum diameter of the largest tumor lesion in the SLN; <0.1, 0.1-1.0, >1.0 mm), invasion depth (depth of tumor invasion measured from the capsule in the SLN; SI ≤ 0.3 mm, SII >0.3 to ≤ 1.0 mm, SIII >1.0 mm), and microanatomic location (microanatomic location of the tumor deposits within the SLN; "subcapsular", "parenchymal", "combined", "multifocal", "extensive"). A retrospective study, using prescribed survey forms, was carried out. Among the 450 patients, including the 149 cases with SLN metastasis, an additional lymph node positivity rate of 0% could be predicted only in patients with a maximum diameter category of less than 0.1 mm. As compared with that in the SLN metastasis-negative cases, however, the prognosis was poorer in cases with SLN metastasis, even those with lesions falling under the maximum diameter category of less than 0.1 mm, invasion depth category of SI (≤ 0.3 mm) and microanatomic location category of subcapsular. The prognosis is particularly poor for the microanatomic location category of extensive, which should thus be regarded as a macrometastasis. A prospective study with standardized procedures, including pathological evaluation, is needed in order to confirm our conclusion.