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.

Two cases of infundibular squamous cell carcinoma on the nose with aggressive clinical behavior: Case report and review of the published work.

Case 1 was a 75-year-old Japanese man who presented with a poorly demarcated, dark-red nodule with a destructive defect in the center, measuring 3 cm × 2 cm on the right wing of his nose. The histological diagnosis was a common form of infundibular squamous cell carcinoma. Atypical neoplastic cells radiated from the wall of a follicular infundibulum. The majority of neoplastic cells were positive for AE1/AE3 and 34ßE12. Cytokeratin 17 expression was seen in the suprabasal cells of the deeply situated neoplastic components. Case 2 was a 73-year-old Japanese man who presented with a poorly demarcated, dark-red nodule with an irregularly shaped ulcer in the center, measuring 3 cm × 2 cm on the left wing of his nose. The histological diagnosis was a crater form of infundibular squamous cell carcinoma. Atypical neoplastic cells radiated from the broad base of the central keratin-filled crater, continuous with two infundibular canals. In both cases, some of the more deeply situated aggregations were composed of neoplastic keratinocytes with eosinophilic glassy or pale cytoplasm. In addition, no atypical keratinocytes could be seen in the interfollicular epidermis. In case 1, a hematogenous metastasis to the vocal cord and the forehead occurred in addition to a lymph node metastasis. In case 2, a local recurrence occurred with an intralymphatic dissemination. We describe two cases of infundibular squamous cell carcinoma on the nose with aggressive clinical behavior, one of which was accompanied by a hematogenous metastasis while another revealed a local recurrence.

Spindle cell squamous cell carcinoma arising in Bowen's disease: Case report and review of the published work.

A 79-year-old Japanese woman presented with an ulcerated, brown-red nodule in the center of a sharply demarcated, tan-brown plaque situated on the left side of her right breast. Histologically, the plaque demonstrated an acanthosis with an intraepidermal epithelioma of Borst-Jadassohn. Small oval nests of bland-appearing basophilic cells in the periphery gradually enlarged into nests of various sizes and irregular shapes, composed of densely cohesive, atypical basophilic cells above the central nodule. The atypical keratinocytes shifted to atypical spindle cells beneath the acanthotic epidermis, penetrating deep into the subcutaneous tissue. In addition to vimentin and p63, the spindle cells were positive for several cytokeratin (CK) markers, including AE1/AE3, 34ßE12 and CK5/6, which showed more intense signals closer to the epidermis. Basophilic cells in the clonal nests were positive for p63, AE1/AE3, 34ßE12 and CK5/6. The MIB-1 index was estimated at approximately 40-50% in both the bland-appearing and the atypical basophilic cells. We describe the first case of spindle cell squamous cell carcinoma arising in an intraepidermal epithelioma expressed by clonal Bowen's disease, which was difficult to differentiate from clonal seborrheic keratosis.