In-transit recurrence of Merkel cell carcinoma associated with Bowen's disease: The first reported case successfully treated by avelumab.

A 65-year-old Japanese man presented with a dome-shaped nodule, the base of which was contiguous with a dull brown plaque, on the left leg. After local excision of the cutaneous lesion and left inguinal lymph node dissection, several dermal and subcutaneous nodules developed successively on the left lower extremity. Hematoxylin-eosin staining of the primary cutaneous lesion demonstrated uniform neoplastic cells arranged in a trabecular pattern extending from the dermis to subcutis. Mitotic figures were abundant. Although the overlying epidermis was substantially intact, the Merkel cells had invaded the epidermis, resulting in Pautrier-like microabscesses. The hyperplastic epidermis adjacent to the nodule consisted of abnormally growing atypical keratinocytes. The enlarged left inguinal lymph node and successive secondary nodules contained Merkel cells similar to those in the primary nodule. Immunohistochemically, most tumor cells were positive for CAM5.2, synaptophysin, chromogranin A, CD56 and vimentin. The tumor cells in the left inguinal lymph node were positive for CAM5.2, synaptophysin and cytokeratin 20 but negative for CM2B4, and less than 1% of the cells expressed programmed cell death ligand 1. The patient was treated with avelumab, which showed significant efficacy against the in-transit recurrence. Two months later, all nodules had disappeared completely. We describe a case of in-transit recurrence of Merkel cell carcinoma that was associated histologically with Bowen's disease and was successfully treated with avelumab. Although accumulation of additional cases is needed, avelumab therapy may be a useful treatment for in-transit recurrence of Merkel cell carcinoma.

Indeterminate dendritic cell neoplasm accompanied by eosinophilic pneumonia successfully treated by systemic steroid therapy: Report of the first case with muscular and parotid involvement and review of published work.

A 34-year-old Japanese man presented with an indolent nodule on the right flank. Computed tomography of the chest and abdomen demonstrated a large nodule measuring 55 mm × 50 mm in the abdominal oblique muscle layer of the right flank, and several small nodules were seen in the muscle layer throughout the body and subcutaneous tissue of the lower abdomen. 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography revealed nodular lesions in the bilateral parotid glands, bilateral cervical lymph nodes and lower lobe of the right lung. Intermittently, ground-glass shadows developed in the bilateral lungs. Histologically, sheet-like nodules in the abdominal oblique muscle layer and parotid gland were composed of large polygonal cells with convoluted nuclei and ample eosinophilic cytoplasm. Several lymphocytes and considerable eosinophils were intermingled. Lung biopsy demonstrated an inflammatory infiltrate of lymphocytes and considerable eosinophils in the alveoli. Immunohistochemically, polygonal cells were positive for S100 protein and CD1a, but negative for langerin and BRAFV600E . Some cells were positive for CD68. Electron microscopy demonstrated histiocytic cells with phagosomes and interdigitating processes. However, no Birbeck granules were observed. Eosinophilia was seen in the peripheral blood. Multifocal nodules and ground-glass shadows gradually diminished following systemic administration of oral prednisolone. We describe a case of indeterminate dendritic cell neoplasm with multifocal involvement of the muscle, subcutis, lymph node and parotid gland accompanied by chronic eosinophilic pneumonia that was successfully treated by systemic steroid therapy. Neither muscular nor parotid indeterminate dendritic cell neoplasms accompanied by eosinophilic pneumonia have been previously reported.

Pseudovascular squamous cell carcinoma: A review of the published work and reassessment of prognosis.

A 90-year-old Japanese woman presented with a dome-shaped, dark-red, ulcerated nodule measuring 23 mm × 19 mm × 9 mm on the right side of the nasal root. Histologically, anastomosing cord-like arrays of atypical polygonal keratinocytes exhibiting internal pseudolumina containing detached cells and erythrocytes were observed. Although acantholytic and cohesive areas overlapped, cancer pearls were not detected. The lower epidermis partially demonstrated scattered dyskeratotic and acantholytic keratinocytes with loss of polarity, continuous with an underlying tumor mass. The tumor cells were positive for a variety of cytokeratins, p40 and vimentin. The Ki-67 proliferation index was 50-60%. Both CD31 and CD34 were expressed in reactive blood vessels of the tumor. A local excision margined by 1 mm was performed, followed by X rays and electron beam irradiation. Neither lymph node nor distant metastasis has appeared over the 14 months since the excision. We performed a review of the published work and identified 24 previously reported patients with pseudovascular squamous cell carcinoma of the skin, oral mucosa and vulva to reassess the prognosis of this tumor. In 12 of these patients (50%), sites other than the head and neck were involved. Eight (33%) tumor-associated deaths occurred. It is believed that pseudovascular squamous cell carcinoma has a tendency to develop at morbid skin and mucous membranes sites in organs other than the face and neck and to possess an aggressive clinical behavior.

Urinary cystatin C as a biomarker for acute kidney injury and its immunohistochemical localization in kidney in the CDDP-treated rats.

Cystatin C, a cysteine protease inhibitor, is a novel biomarker of renal damage. In the present study, we examined the urinary and plasma levels of cystatin C and how useful they are for the early detection of acute kidney injury (AKI) in CDDP-treated rats in comparison with other biomarkers (ß2-microglobulin, calbindin, clusterin, EGF, GST-α, GST-µ, KIM-1, NGAL, osteopontin, TIMP-1, and VEGF). The urinary levels of cystatin C, GST-α, KIM-1, and EGF changed prior to proximal tubule damage and increases in plasma urea nitrogen and creatinine levels, suggesting their usefulness for predicting AKI. On the other hand, the plasma cystatin C level hardly changed. We also investigated the localization of cystatin C in the kidney according to the progression of renal damage. Cystatin C was predominantly localized in the proximal tubule of the cortex, and its immunohistochemical expression was not affected by CDDP treatment. In addition, cystatin C was observed in the lumen of the renal tubule in the cortex, cortico-medullary junction, and medulla during the progression of renal damage, although its immunoreactive area ratio was very low. In conclusion, urinary cystatin C measurements can detect CDDP-induced AKI as early as KIM-1, GST-α, and EGF in rats, although the change ratio of the cystatin C was smaller than others. Immunohistochemical cystatin C expression in the proximal tubule of the kidney was hardly changed by the CDDP treatment, but it was newly observed in the renal tubule lumen after CDDP treatment.

Cisplatin (CDDP)-induced acute toxicity in an experimental model of hepatic fibrosis.

Cisplatin (CDDP)-induced acute toxicity was investigated in an experimental model of liver fibrosis produced through repeated intraperitoneal injections of swine serum in rats. A significant increase in level of hepatic markers, such as plasma ASAT, LDH, glucose, total cholesterol and bile acid levels, and a significant decrease in the plasma triacylglycerol level were observed. Slight histological changes, such as necrosis, vacuolar degeneration, and the proliferation of bile ducts were observed as compared with the control fibrotic rats. On the other hand, a significant increase in levels of renal markers, such as plasma BUN and creatinine levels as well as more remarkable tubular degeneration were observed. From these results, CDDP's hepatotoxicity was slight while its nephrotoxicity was more extensive in fibrotic rats.

Immunohistochemical localizations of secretin, cholecystokinin, and somatostatin in the rat small intestine after acute cisplatin treatment.

Cisplatin (CDDP) is an antitumor platinum complex that causes the well-studied side effect of renal tubular failure. In the present study, the acute effects of CDDP treatment on the localization of gut hormones in the rat small intestine were examined by immunohistochemistry. Male Sprague-Dawley rats were used for these experiments. Rats were injected intravenously with CDDP (3 mg/kg) in saline or were left untreated (control). After the rats were euthanized at 1, 3, 5, or 10 days after CDDP treatment, the small intestines (duodenum, jejunum, and ileum) were quickly removed, fixed, embedded in paraffin, and cut. No mucosal toxicity was detected by histopathological observation in any of the intestines of CDDP-treated rats. The immunohistochemical detection was performed using anti-secretin, anti-cholecystokinin (CCK), and anti-somatostatin with the avidin-biotin-immuno-peroxidase procedure. The total number of immunoreactive cells per complete cross-section was counted. In the duodenum, the numbers of secretin-immunoreactive cells and somatostatin-immunoreactive cells were dramatically increased 5 days after CDDP treatment. In the jejunum, the number of CCK-immunoreactive cells was increased 1 day after CDDP treatment and those of secretin-immunoreactive cells and CCK-immunoreactive cells were increased 5 days after CDDP treatment. In the ileum, the number of CCK-immunoreactive cells was increased 1 day after CDDP treatment. The change in the secretin-immunoreactive cell count may be caused by metabolic inhibition of gastrin following CDDP-induced nephrotoxicity. The change in the CCK-immunoreactive cell count may promote the excretion of bile. Therefore, somatostatin may regulate secretin and CCK secretion. We conclude that the distribution of these hormone-immunoreactive cells in the rat small intestine might be controlled by CDDP-induced nephrotoxicity without gut mucosal toxicity.