Hirotsugu Tanimura

Elevated serum BAFF levels in patients with sarcoidosis: association with disease activity

OBJECTIVE The purpose of this study was to determine serum levels of B-cell-activating factor (BAFF) and its clinical association in patients with sarcoidosis. METHODS; Serum levels of BAFF from 37 patients and 21 healthy subjects were examined by ELISA. Serum angiotensin-converting enzyme (ACE), lysozyme and IFN-γ levels in sarcoidosis patients were also measured. Isolated monocytes cultured with IFN-γ, IL-4 or IL-10 and their expression of membrane and soluble BAFF were analysed by flow cytometry or ELISA. Peripheral B cell subsets were analysed by flow cytometry. BAFF expression in the granuloma of the skin was examined by immunohistochemistry. ANAs were determined by indirect IF using HEp-2 cells as a substrate. RESULTS Serum BAFF levels were significantly elevated in sarcoidosis patients when compared with healthy controls. The frequency of skin and eye involvement was significantly higher in patients with elevated serum BAFF than in patients with normal levels. Serum BAFF levels were correlated with serum levels of ACE, lysozyme and IFN-γ. Immunostaining of anti-BAFF in the skin revealed BAFF expression by epithelioid cells of granuloma. In vitro, IFN-γ induced membrane-bound BAFF expression on monocytes and secretion of soluble BAFF by isolated monocytes. In the peripheral blood, sarcoidosis patients showed increased naïve B cells with a reciprocal decrease in memory B cells and plasmablasts. Seventeen of 26 (65%) sarcoidosis patients exhibited ANA positivity. CONCLUSION Serum BAFF levels can be used as a surrogate marker of disease activity in sarcoidosis patients. Increased BAFF may be related to the pathogenesis of sarcoidosis.

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 34βE12. 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.

Solar urticaria with a wide action spectrum from UVB to visible light complicated with UVA-induced polymorphous light eruption.

To the Editor, Solar urticaria and polymorphous light eruption (PLE) are acquired idiopathic photosensitivity disorders, but each phenomenon is extremely different; one is an immediate reaction, and one is a delayed-type reaction. Phototesting is necessary not only for the diagnosis of these photosensitivity disorders but also for the determination of the action spectrum so that the patient can try to avoid the triggering wavelengths in ordinary life. Solar urticaria is unique in that the particular spectra that inhibit or enhance the reactions by action spectra are present in some cases. In contrast, with PLE, phototesting is difficult, because a single or even repeated exposure of ultraviolet light or visible light sometimes fails to provoke the reaction. Here, we report a case of solar urticaria complicated with PLE. Solar urticaria with an action spectrum ranging from UVB to visible light was diagnosed by clinical presentation, phototesting and intradermal injections of photo-irradiated autologous serum. PLE induced by UVA was diagnosed by clinical presentation and phototesting. A 60-year-old man experienced erythematous skin eruptions on sun-exposed areas immediately after exposure to sunlight while riding a bicycle. The eruptions disappeared within 1 hour. The next day, he went fishing in the sun and experienced pruritic erythema and swelling on the face and dorsal surface of the hands. The swelling improved within a few hours, but erythema persisted until the following day. He is otherwise healthy and takes no medications. There were no abnormal laboratory findings, including antinuclear antibody and porphyria profiles. Photoprovocation tests were performed with a sunlamp (Philips Ultra Violet-B TL 20W12, Eindhoven, The Netherland) for UVB, a black light (Torex FL 20S, BL-BMR, Tokyo, Japan) for UVA and a slide projector (160W; Cabin Kogyo Co, Tokyo, Japan) for visible light. A single exposure to 3.0 J/cm of UVA (Fig. 1a), 8.7 mJ/cm of UVB (Fig. 1b) or visible light (Fig. 1c) at the target distance of 15 cm for 15 min induced erythema or wheal immediately after exposure. Erythema was observed in a visible light-irradiated area with a Y-50 cut-off filter (Fig. 1d), but not with a Y51 filter (Fig. 1e), indicating that the action spectrum in the visible light wavelengths was shorter than 500 nm. Skin reactions provoked by UVB and visible light faded within 45 min, but those provoked by UVA persisted for 30 h (Fig. 2a–c). Histological examination of the skin reaction 30 h after UVA irradiation revealed spongiosis and dense perivascular mononuclear cell infiltrations (Fig. 2d), compatible to polymorphous light eruption. Inhibitory and augmentation spectra were not observed. Next, the serum of the patient was examined for the presence of chromophore to induce urticaria. An aliquot of serum was exposed in vitro to 1.5 J/cm of UVA, 104 mJ/cm of UVB or 5 min of visible light alone or with an R60 cut-off filter; 0.1 ml of the exposed and

A first reported case of metastatic anorectal amelanotic melanoma with a marked response to anti-PD-1 antibody nivolumab: A case report

Highlights • We report a first case of nivolumab reduction of metastatic anorectal amelanotic melanoma (AAMM).• Multimodal therapy including nivolumab will be effective also for non-cutaneous AAMM.

Retiform hemangioendothelioma presenting as a pedunculated nodule on the site of an inguinal pyoderma chronica

tomeningeal enhancement (MRI). When setting the mutation frequency exceed 1% as mutation-positive standard, the affecting tissue is GNAQ mutation positive with the frequency of 3.86%. Above all, our patient can be diagnosed with SWS. However, her symptom belongs to salmon patch through distribution of the lesion but PWS with SWS by her genetic and radiological study. This is the first case of SWS by genetic analysis with capillary malformation in the middle, which challenges the formal published work in that salmon patch does not reflect mosaicism. As physicians, we can easily overlook such facial midline CM by diagnosing it as salmon patch and excluding SWS formation of an early stage. As such, apart from careful physical examination, medical history taking as well as radiology, biopsy and NGS if necessary are recommended when evaluating infants with CM in the midline of the face to prevent SWS. Further study on its relationship with facial midline CM and GNAQ mutation is required.

CD1a-positive cutaneous mastocytosis: Electron microscopic evidence of pleomorphic mast cell proliferation

Dear Editor, A 1-year-old boy presented with slightly infiltrative brown papules and plaques scattered on his trunk and extremities (Fig. 1a), exhibiting Darier’s sign. His family had noticed the rash during his infancy. Dermoscopic examination showed homogeneous brown pigmentation reflecting diffuse deposits of melanin granules in the basal layer. Hematoxylin–eosin staining revealed moderate cell infiltration in the papillary dermis and superficial perivascular area (Fig. 1b), which is composed of pleomorphic cells with irregularly shaped nuclei and ample basophilic cytoplasm (Fig. 1c). Giemsa staining revealed a positive metachromatic reaction (Fig. 1d). Immunohistochemical examination demonstrated strong positivity for c-kit (Fig. 1e) and CD1a (Fig. 1f) and negativity for S100 protein and langerin in pleomorphic cells. Although double staining could not be done, CD1a was stained in c-kit-positive pleomorphic cells judging from the morphology. CD68 staining was positive in a few bystander cells. On electron microscopy, proliferating cells exhibited intricate villous processes and many round cytoplasmic granules (Fig. 1g). The round granules were partly lamellar or whorled and included

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.

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. 18F‐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.

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, 34βE12 and CK5/6, which showed more intense signals closer to the epidermis. Basophilic cells in the clonal nests were positive for p63, AE1/AE3, 34βE12 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 Bowens disease, which was difficult to differentiate from clonal seborrheic keratosis.