Toshihiko Hoashi

Eczematous reactions mimicking psoriasiform dermatitis induced by nivolumab for advanced lung cancer

1. Stockman A, Delanghe J, Geerts M-L et al. Diffuse plane normolipaemic xanthomatosis in a patient with chronic lymphatic leukaemia and monoclonal gammopathy. Dermatology 2002; 204: 351–4. 2. Spanou Z, Borradori L. Diffuse plane xanthomas, a cutaneous marker for monoclonal gammopathies and lymphoproliferative diseases. Eur. J. Haematol. 2011; 86: 91. 3. Gadzia J, Kestenbaum T. Granulomatous slack skin without evidence of a clonal T-cell proliferation. J. Am. Acad. Dermatol. 2004; 50: 4–8. 4. Marcoval J, Moreno A, Bordas X et al. Diffuse plane xanthoma: clinicopathologic study of 8 cases. J. Am. Acad. Dermatol. 1998; 39: 439–42.

Case of nodular melanoma on the upper eyelid dermoscopically mimicking pigmented basal cell carcinoma

asymptomatic pigmented skin lesion in the lumbar area. Physical examination revealed a 9 mm 9 4.5 mm papule with regular borders and multiple colors (Fig. 1a). Dermoscopic evaluation showed an asymmetrical polychromic lesion with an atypical pigmented network and milky red areas (Fig. 1b). The diagnosis of malignant melanoma was suspected and reflectance confocal microscopy (RCM) was performed. At epidermal layers, RCM showed a normal honeycombed pattern without evidence of pagetoid spreading. Mosaic images at the dermoepidermal junction showed two differential areas (Fig. 1c). The dermoscopic pigmented network correlated with widespread circular structures with clear borders forming a hyperrefractile meshwork. Each circular silhouette was composed of hyperrefractile strands and cords centered by a black hole (fenestration). At the dermal level, abundant melanophages and tortuous vessels were shown throughout the lesion. (Fig. 1e,f). Reflectance confocal microscopy excluded the possibility of melanoma and was more consistent with a basaloid tumor. Histopathological examination confirmed the diagnosis of FeP (Fig. 1g–i). Fibroepithelioma of Pinkus is an unusual neoplasm, which is considered a rare and low-risk variant of basal cell carcinoma. Fibroepithelioma of Pinkus presents clinically as a slowgrowing solitary hypopigmented papule, plaque, nodule or sessile tumor located on the trunk. A pigmented variant is occasionally observed. The main clinical differential diagnosis includes several nonmalignant cutaneous lesions such as intradermal and compound melanocytic nevus, seborrheic keratosis, neurofibroma, pyogenic granuloma and skin tags. Dermoscopic features of FeP were first reported in 2005 by Zalaudek et al. According to the largest series, the lesions are usually red to light brown and show fine arborizing vessels (either alone or associated with dotted vessels). In nine of 10 cases, white streaks were found. In pigmented cases, structureless gray-brown areas of pigmentation and variable numbers of grayblue dots were found. In a more recent article by Longo et al., features of hyperand hypopigmented FeP were distinguished. Whereas hypopigmented FeP showed white intersecting lines with a vascular pattern, hyperpigmented tumors showed ulceration, patchy hyperpigmented areas and brown dots. Reflectance confocal microscopic features of FeP were first described by Viera et al. in 2008 as dark tumor silhouettes with clefting surrounded by thickened collagen at the dermoepidermal junction. Longo et al. further described FeP features. According to these authors, FeP is characterized by the presence of cords or tumor islands with peripheral palisading cells arranged in a fenestrated pattern. Most recent reports describe similar fenestrated confocal pattern at the dermoepidermal junction, with the presence of numerous plump bright cells in the superficial dermis in cases of pigmented tumors. Microscopically, FeP is comprised of thin strands of basaloid cells that anastomose around a fibroblast-rich stroma which correlates with the fenestrated pattern seen under RCM. In this case, pigmented fenestrated structures were interpreted under dermoscopy as a real pigment network, suggesting the dermoscopic diagnosis of a malignant melanoma. A pigment network has not been previously described in FeP. RCM examination provided the clue to establish a proper diagnosis.

Chronic tophaceous gout with multiple large tophi.

Thus, results from previous studies may not reflect the actual prevalence of fronto-vertex baldness in the general population. Second, skull-cap pattern baldness presents as fronto-vertex baldness without anterior hairline recession. Therefore, men with skull-cap pattern baldness may not recognize hair loss until they are diagnosed with AGA by a doctor. We found that more than half of men with AGA showed fronto-vertex hair loss, with a higher frequency of vertex baldness than frontal baldness. We also found that approximately one-fifth of the men had skull-cap pattern baldness in the general community. Therefore, physicians should more carefully examine the hair on the frontal and vertex hair when diagnosing AGA in men. It could facilitate the diagnosis of AGA leading to early treatment for baldness.

Case of subungual malignant melanoma showing the subtle clinical features and unexpected typical histopathological findings of melanoma in situ

Dear Editor, Subungual melanoma is a variant of cutaneous melanoma. A 65-year-old Asian right-handed woman was referred to our hospital for evaluation of pigmentation of the right thumbnail. She had noticed the pigmentation 3 months previously. The nail showed brownish longitudinal pigmentation of approximately 3.7-mm width (Fig. 1a). Borders were not clear and color variation was not prominent. Dermoscopic observation also showed subtle brownish pigmentation with an ambiguous border (Fig. 1b). Brownish pigmentation on the proximal nail fold, so-called Hutchinson’s sign, clearly seemed to be successive to the pigmented nail band (Fig. 1b, arrow), although we could not establish this by naked-eye inspection. There was no pigmentation on the lateral nail folds or on the hyponychium. We resected under the diagnosis of subungual melanoma in situ. Histopathologically, scattered melanocytes were seen in the basal and suprabasal layers of the keratinocytes of the nail matrix (Fig. 1c, arrows). Some of them were hyperchromatic and atypical (Fig. 1c, dotted arrow). Neither nest formation nor mitosis was observed. MART-1 staining was performed to visualize the melanocytic cells. MART-1-positive cells harboring long dendrites were seen in the suprabasal layer of the nail matrix (Fig. 1d). Importantly, MART-1-positive cells were more abundant in the basal layer of the proximal nail fold (Fig. 1e). A splitthickness skin graft from the sole skin was performed. After 6 months, there was neither sign of local recurrence nor that of distant metastasis. A subungual melanoma usually originates from the nail matrix, then spreads to the adjacent nail bed, the hyponychium and/or the nail folds, and invades the dermis and finally the bone. Pigmentation of the nail folds and the cuticle, which is referred to as Hutchinson’s sign, is an important clinical clue in the diagnosis. Lymphatic assessment

Two Cases of Verrucous Carcinoma: Revisiting the Definition

Verrucous carcinoma (VC) is an uncommon, distinct type of well-differentiated squamous cell carcinoma. Here we present two cases of VC, one arising from the lower leg and the other from genital skin. Case 1, a female patient, aged 95 years, had a brownish verrucous plaque on her right lower leg. Histopathologically, epithelial tumor cells grew pushing the stroma, while the basement membrane was intact. No prominent cellular atypia or hyperchromatin was found. Case 2, a male patient, aged 53 years, had a verrucous plaque at the border between his scrotum and inner aspect of his thigh. A pathological diagnosis of VC was made using an excisional specimen. Making a definitive diagnosis of VC is challenging but crucial. Pathological diagnosis using a small specimen might cause underdiagnosis or overdiagnosis. To avoid this, pertinent pathological diagnosis using an ample specimen is required. We also revisited the definition of VC to precisely understand its nature.

Atypical pemphigus developed in a patient with urothelial carcinoma treated with nivolumab

melanoma in adults, such as Hutchinson sign, broad pigment band and nail dystrophy. In addition, although rare, there have been some reports of childhood LM that have resulted from melanoma. To better manage the childhood LM, accumulation of the data about the natural course of its clinical features, especially over the long term, is necessary. Here, we report a clinical course of childhood LM followed up for 10 years. A 1-year-old Japanese girl was referred to our department for a linear pigmentation on the nail of her right index finger. Her parents noticed the pigmentation when she was 10 months old. The pigmentation gradually enlarged and became 3.5 mm wide on her first visit (Fig. 1a). The clinical appearance showed a homogeneous, blackish-brown pigmentation with a sharp lateral border. A nail dystrophy was observed at the tip of the nail. In addition, a small brownish pigmentation was observed at the fingertip by dermoscopy (Fig. 1g). We diagnosed the pigmentation as LM due to congenital melanocytic nevus or lentigo, and decided to take a “wait and see” approach. At the age of 2 years, the LM lesion was further enlarged and the color at the proximal part of the nail plate progressed to blackish (Fig. 1b). The pigmentation spread all over the nail at the age of 3 years, and has subsequently maintained that distribution (Fig. 1c–f). On the other hand, the pigmentation on the fingertip (Fig. 1h) gradually regressed and had almost disappeared by the age of 11 years (Fig. 1i). The nail deformity also improved, becoming a minimal distal fissure. The patient is still under follow up once a year. Clinical features of LM that raise concern for melanoma include a broad pigment band (broader than 3 mm), change in pigmentation or shape, nail dystrophy, Hutchinson sign, nonhomogeneous color, blurred lateral borders, irregular lines that are not parallel on dermoscopy and rapid evolution. Although our case showed some of these worrisome features, such as a broad pigment band, change in pigmentation/shape, nail dystrophy and Hutchinson sign, the pigmentation was homogenous with clear lateral borders. In addition, the nail dystrophy was mild and limited only at the tip. Furthermore, the dystrophy and Hutchinson sign almost disappeared during the follow up. These clinical manifestations are strongly indicative of LM due to benign nevi. Considering the difficulty of histological diagnosis and the risks of surgical complications, biopsy for childhood LM should be performed with extreme caution. Further accumulation of the long-time follow-up data would lead to better management of childhood LM.

Severe myalgia associated with brodalumab treatment in a patient with psoriasis

Dear Editor, Recent clinical trials have demonstrated the efficacy and safety of biologics for moderate to severe psoriatic patients. We describe here the first case of severe myalgia associated with brodalumab, an anti-interleukin (IL)-17 receptor antibody, which was administrated to a psoriatic patient but then discontinued. A 51-year-old Japanese woman with severe psoriasis was referred to our department for systemic treatment. Brodalumab 210 mg was injected into her lower abdomen at weeks 0, 1 and 2 followed by every 2 weeks until week 8. The Psoriasis Area and Severity Index score was dramatically improved from 11.6 at week 0 to 0.8 at week 4. Before brodalumab injection, all laboratory data were within normal limits, including the creatine kinase (CK) level (56 U/L; normal range, 60–170). At week 1, the patient started to complain of myalgia, which was gradually exacerbated as time passed (Table 1). Two days after week 8, she visited us complaining of severe myalgia mainly in her upper extremities. Although the CK level was still within the normal limit (78 U/L), manual muscle testing disclosed that muscular strength on the upper extremities had become slightly weaker and her grip strength was 14.0 kg/16.0 kg (left/right) (Table 1). Thyroid function tests were normal and she was negative for acetylcholine receptor antibodies. The myalgia was gradually resolved after the discontinuation of brodalumab. At week 15 (7 weeks after the discontinuation) the myalgia was almost completely resolved, manual muscle testing showed almost normal results, and grip strength returned to the normal level, 30.0 kg/30.0 kg (left/right) (Table 1). According to the brodalumab prescribing information (www.accessdata.fda.gov/drugsatfda. . ./761032lbl.pdf), myalgia occurred in 1.7% of subjects in a brodalumab group (n = 1496), in 0.3% with a placebo (n = 879) and in 0.7% with ustekinumab (n = 613), an anti-IL-12/23 monoclonal antibody. To the best of our knowledge, there has been no report of brodalumab-associated myalgia that is severe enough to result in cessation of the drug. Hinojosa et al. reported severe myalgia associated with adalimumab, an anti-tumor necrosis factor-a antibody, in a patient with Crohn’s disease. Interestingly, their case and our case have several points in common: myalgia, especially in upper extremities, was severe enough to result in discontinuation of the drugs, the results of all laboratory tests were within normal limits, including CK, the occurrence and improvement of the symptoms showed a serial order following introduction and withdrawal of the drugs, and, based on the Naranjo algorithm, the adverse reaction was scored as “probable”. Although the precise mechanism of myalgia associated with adalimumab and brodalumab is unknown, muscle tissue is highly sensitive to many drugs because of its high metabolic activity. Additional differential diagnoses include side-effects of other drugs and infections; however, their possibilities seem

Case of primary cutaneous anaplastic large cell lymphoma misdiagnosed as squamous cell carcinoma by pseudocarcinomatous hyperplasia

Dear Editor, Primary cutaneous anaplastic large cell lymphoma (pcALCL) is very rare and is sometimes difficult to diagnose. In some pcALCL cases, local treatments are not sufficient and systemic therapies are required. An Asian male patient, aged 65 years, had noticed an asymptomatic pinkish painless nodule on the dorsal side of his right foot approximately 2 months previously. It was a well-circumscribed reddish firm cutaneous nodule accompanied by ulceration and surrounding erythematous plaque (Fig. 1a). Pelvic computed tomography (CT) denied lymphadenopathy. Histopathologically, epidermal hyperplasia and prominent vascular proliferation with inflammatory cell infiltration were observed (Fig. 1b). Squamous eddies were observed although atypical keratinocytes were not conspicuous (Fig. 1c). With the diagnosis of well-differentiated primary squamous cell carcinoma, we resected the tumor and reconstructed with a split-thickness skin graft. Granulomatous nodules similar to the initial one gradually proliferated at the periphery of the grafted skin (Fig. 1d). Histology showed no epithelial hyperplasia (Fig. 1e). Numerous small cells, including neutrophils and eosinophils, densely proliferated in the dermis (Fig. 1f). Markedly atypical large epithelioid cells were mixed in. Immunohistochemically, the atypical cells were positive for CD30 (Fig. 1g), epithelial membrane antigen (EMA; Fig. 1h), CD4 and CD25 but were negative for anaplastic lymphoma kinase, CD3, CD8, CD15 and CD56 (data not shown). When the initial biopsy specimen was re-examined, atypical cells harboring large nuclei were found to be positive for CD30 (Fig. 1i). We finally diagnosed pcALCL. Low-dose methotrexate therapy (7.5 mg/week) was selected. The patient was free from the disease 1 year later. Diagnosis of pcALCL is difficult and is challenging based on its clinical features as well as by pathological analysis. In ALCL, pseudocarcinomatous hyperplasia is sometimes observed, which makes the pathological diagnosis difficult as in this case. Pseudocarcinomatous hyperplasia shows early signs of spontaneous regression. Abundant neutrophilic and eosinophilic infiltration seems to indicate infectious disease and masks atypical cells. Solitary or localized lesions of pcALCL are usually treated by surgical excision, irradiation or the combination of the two. When the lesions are multifocal, surgical excision is not recommended. Adequate vertical and horizontal margins are not clearly defined for surgical excision of pcALCL. In this case, the depth might have been acceptable but the horizontal margin was inadequate. It is well known that even incisional biopsy can sometimes completely clear the lesion of pcALCL. Thus, it is very difficult to select cases with pcALCL for which surgical resection is recommended. Anaplastic lymphoma kinase expression is extremely rare in pcALCL and its detection favors systemic disease. The EMA expression in this case raised the possibility of systemic ALCL, but it was denied by the imaging study. Several cases of pcALCL arising on the leg have been reported. Importantly, some of them could not be treated with local therapy and finally required systemic therapy. It may be better to use different treatment strategies for pcALCL based on the location of skin lesions.

Pigmented poroma on the temporal region dermoscopically mimicking basal cell carcinoma: A report of two cases

Dear Editor, Poroma is a benign neoplasm, in which tumor cells differentiate towards poroid and cuticular cells of acrosyringium. A 79-year-old woman (case 1) presented with an 18 mm 9 14 mm, bulb-shaped, light pink semipedunculated nodule with ring-like blackish macules on her left temporal region (Fig. 1a). A 58-year-old man (case 2) exhibited a similar 12 mm 9 12 mm, semipedunculated nubby nodule on his right temporal region (Fig. 1a). Dermoscopic examination revealed thick vessels and large blue-gray ovoid nests in both cases

A case of cutaneous metastatic lung cancer difficult to distinguish from malignant nodular hidradenoma

1. Fitch E, Harper E, Skorcheva I et al. Pathophysiology of psoriasis: recent advances on IL-23 and Th17 cytokines. Curr. Rheumatol. Rep. 2007; 9: 461–7. 2. Ohtsuki M, Morita A, Abe M et al. Secukinumab efficacy and safety in Japanese patients with moderate-to-severe plaque psoriasis: subanalysis from ERASURE, a randomized, placebo-controlled, phase 3 study. J. Dermatol. 2014; 41: 1039–46. 3. Shibata M, Sawada Y, Yamaguchi T et al. Drug eruption caused by secukinumab. Eur. J. Dermatol. 2017; 27: 67–8. 4. Zhang JZ, Maruyama K, Ono I et al. Effects of etretinate on keratinocyte proliferation and secretion of interleukin-1 alpha (IL1 alpha) and IL-8. J. Dermatol. 1994; 21: 633–8.