Masahiko Muto

A case of pemphigus herpetiformis‐like atypical pemphigus with IgG anti‐desmocollin 3 antibodies

decrease dramatically in the late stage of DIHS. Taken together, HMGB1 released during the acute phase of DIHS/ DRESS might facilitate Th2 cell activation induced by the causative drug, resulting in exacerbation. In this context, Th2 cells and Tregs, both producing IL-10, along with other activated cells producing proinflammatory cytokines, characterize the pathophysiology of DIHS/DRESS in the early stage. In conclusion, cytokine storm occurs in various types of cADRs, but factors other than cytokines are required for the onset of severe cADR. HMGB1 may contribute to the development of DIHS/DRESS through Th2 cell activation, which plays a key role together with Tregs in the disease. The involvement of HMGB1 in cADRs therefore requires further investigation.

Drug-induced hypersensitivity syndrome induced by clindamycin.

© 2013 The Authors. doi: 10.2340/00015555-1363 Journal Compilation

Verrucous carcinoma of the foot diagnosed using p53 and Ki-67 immunostaining in a patient with diabetic neuropathy.

To the Editor: Verrucous carcinoma (VC) is a locally invasive, well-differentiated, low-grade squamous cell carcinoma with a low metastatic potential. VC of the foot is rare and presents as an enlarging, cauliflower-like tumor. The clinical findings of VC of the foot are similar to those of verrucous skin lesions on the feet in diabetic neuropathy (VSLDN), making it difficult to distinguish between the 2 conditions. Here, we present a case of VC of the foot in a patient with diabetic neuropathy, which was differentiated from VSLDN by examining p53 and Ki-67 expression using immunohistochemistry. A 66-year old, insulin-dependent diabetic Japanese man was referred to our department with a 6-years history of a verrucous lesion on the right sole. The lesion had been diagnosed as VSLDN by another hospital doctor and treated with topical vitamin D3 analogs and debridement. Response to treatment was poor, and the lesion gradually enlarged. Physical examination revealed a verrucous mass, 6 cm in diameter, with central ulceration and hyperkeratotic borders on the right sole (Fig. 1). In addition, a hyperkeratotic lesion with a central ulceration was observed on the left sole, which was consistent with diabetic ulcer. Neurological examination revealed peripheral neuropathy with sensory disturbance on the feet, consistent with a diagnosis of diabetic neuropathy. Computed tomography showed no evidence of lymphadenopathy or malignancy. Histopathological examination of a punch biopsy specimen taken from the verrucous lesion on the right sole revealed invasive projections of epithelium with some vacuolated keratinocytes in the upper epidermal layers and lymphocyte infiltration in the adjacent dermis (Fig. 2A). Large keratinocytes with large nuclei, minimal atypia, and mitotic figures were observed in the basal and suprabasal cell layers (Fig. 2B). Immunohistochemical analysis showed that the ratio of p53-positive cells to p53negative cells in the basal epidermis was 58.3% (Fig. 2C). Expression of p53 and Ki-67 was detected in basal and suprabasal cells in the lower third of the neoplastic epidermis (Figs. 2C, D). Neither immunohistochemical analysis (K1H8, Dako) nor polymerase chain reaction detected human papillomavirus antigen in the lesion. Based on these findings, the lesion on the right sole was diagnosed as VC. Excision with an 1-cm margin was performed under general anesthesia, and the diagnosis of VC was confirmed after histopathological analysis of the excised specimen. Recurrence was not observed at the 12month follow-up. VC was first described by Ackerman in 1948, appearing in the oral cavity as a well-differentiated, slowgrowing neoplasm with a tendency for local recurrence but not metastatic spread. Distinguishing VC from benign lesions is difficult because the epidermis shows minimal atypia. VSLDN was first described by Gerbig and Hunziker in 1995. Although the precise pathogenesis of VSLDN is unclear, both VSLDN and diabetic ulcer are thought to be due to chronic pressure or friction in an area of sensory loss. VC occurs preferentially on the foot and usually appears as a warty tumor that may resemble VSLDN. In this case, the patient had been diagnosed with VSLDN, and the right sole lesion did not respond to topical treatment and debridement. A case of VC of the foot developing in a chronic pressure ulcer has been reported. Malignant transformation of a pressure ulcer is rare, with a reported incidence of about 0.5%. Although an association between diabetic ulcer and VC has not been previously demonstrated, the presence of diabetic ulcer in the opposite foot in this case raised the possibility of VC developing from diabetic ulcer. It has been reported that p53 immunostaining is useful for distinguishing between VC and VSLDN because p53 positivity in the basal epidermis in the former is higher than FIGURE 1. A verrucous mass with central ulceration and hyperkeratotic borders was observed on the right sole. In addition, a hyperkeratotic lesion with a verrucous surface and central ulceration was observed on the left sole.

Spiny keratoderma of the palms in an insulin-treated diabetic patient

1 Hanke CW, Bailin PL, Roenigk HH Jr. Annular elastolytic giant cell granuloma. A clinicopathologic study of five cases and a review of similar entities. J Am Acad Dermatol 1979; 1: 413–421. 2 Ozkaya-Bayazit E, Buyukbabani N, Baykal C, et al. Annular elastolytic giant cell granuloma: sparing of a burn scar and successful treatment with chloroquine. Br J Dermatol 1999; 140: 525–530. 3 Dell’ana ML, Picardo M. A review and a new hypothesis for non-immunological pathogenetic mechanisms in vitiligo. Pigment Cell Res 2006; 19: 406– 411. 4 Schallreuter KU, Moore J, Wood JM, et al. In vivo and in vitro evidence for hydrogen peroxide (H2O2) accumulation in the epidermis of patients with vitiligo and its successful removal by a UVB-activated pseudocatalase. J Investig Dermatol Symp Proc 1999; 4: 91–96. 5 Ines D, Sonia B, Riadh BM, et al. A comparative study of oxidant-antioxidant status in stable and active vitiligo patients. Arch Dermatol Res 2006; 298: 147– 152. 6 Yildirim M, Baysal V, Inaloz HS, Can M. The role of oxidants and antioxidants in generalized vitiligo at tissue level. J Eur Acad Dermatol Venereol 2004; 18: 683–686. 7 Kawaguchi Y, Tanaka H, Okada T, et al. The effects of ultraviolet A and reactive oxygen species on the mRNA expression of 72-kDa type IV collagenase and its tissue inhibitor in cultured human dermal fibroblasts. Arch Dermatol Res 1996; 288: 39–44. 8 Zaw KK, Yokoyama Y, Abe M, Ishikawa O. Catalase restores the altered mRNA expression of collagen and matrix metalloproteinases by dermal fibroblasts exposed to reactive oxygen species. Eur J Dermatol 2006; 16: 375–379. 9 Igawa K, Maruyama R, Katayama I, Nishioka K. Antioxidative therapy with oral dapsone improved HCV antibody-positive annular elastolytic giant cell granuloma. J Dermatol 1997; 24: 328–331.

Solitary spindle cell xanthogranuloma mimicking a spitz nevus.

To the Editors: Juvenile xanthogranuloma (JXG) contains cells with a wide variety of morphologic characteristics. Five types of JXG have been described: vacuolated, xanthomatized, scalloped, oncocytic, and spindle cell JXG. Spindle cell xanthogranuloma (SCXG) is a rare variant of JXG characterized by a predominance of spindle-shaped cells. It occurs mainly in adults (20–40 years) and less commonly in children. Clinically, SCXG manifests as yellowish to brownish papules and often involves the head, neck, and upper portion of the trunk but may also affect the extremities. Here, we describe an unusual pediatric case of SCXG on the hip presenting as a dark red to bluish nodule with a clinical appearance similar to a Spitz nevus. A 10-year-old Japanese girl was referred to our department with a 6-month history of a solitary, asymptomatic, and gradually enlarging nodule on the left hip without preceding injury to the area. She was otherwise healthy with an unremarkable medical history. Neither the parents nor the siblings had a history of xanthogranulomas. On physical examination, the nodule was dark red to bluish, 10 · 5 mm in size, firm with an ulcerated center (Fig. 1A). Dermoscopic examination revealed white streaks on a blue background around the periphery of the lesion (Fig. 1B). The results of routine laboratory investigations were within normal limits, including an absence of hyperlipidemia. Our initial diagnosis was a Spitz nevus; an excoriated prurigo nodule would be another possible clinical differential diagnosis. The lesion was surgically removed under local anesthesia several weeks after the initial visit. Histopathological examination of the excised specimen showed dense spindle cell proliferation with a storiform pattern associated with Touton multinucleate giant cells in the dermis (Figs. 2A–C). Extensive hemosiderin deposition was noted in the upper dermis (Figs. 2C and 3A). Neither acanthosis nor hyperpigmentation of the overlying epidermis was present. Immunohistochemically, the lesional cells were strongly positive for CD68 (Fig. 3B) but negative for S100 protein, CD1a, Melan-A, HMB45, c-Kit, CD34, smooth muscle actin, and factor XIIIa. From the clinical and histological findings, we diagnosed the lesion as SCXG. No recurrence was noted at 1-year followup. SCXG is non-Langerhans cell disease (xanthogranuloma family) described by Zelger et al. Clinically, SCXG typically occurs in young adults and manifests as a yellow-brown papules affecting—in decreasing frequency—the head, neck, upper trunk, and occasionally, the extremities. Histologically, SCXG is composed predominantly of spindleshaped cells arranged in a storiform pattern. Only a handful of cases of solitary SCXGs have been reported after the initial report by Zelger et al. SCXG may clinically resemble a dermatofibroma (DF). According to Zelger et al, 7 of their 12 cases were initially misdiagnosed as DF/ benign fibrous histiocytoma. In our case, the initial diagnosis was a Spitz nevus because the lesion was a dark red to bluish nodule, and dermoscopy revealed white streaks on a blue background around the periphery of the lesion. The presence of extensive hemosiderin deposition may have also led to the misdiagnosis. The dermoscopic features of JXG were recently described as a “setting sun” appearance with clouds of pale yellow globules, linear and branched vessels,

Subepidermal calcified nodule of the knee with transepidermal elimination of calcium

1 Gambichler T. Mid-dermal elastolysis revisited. Arch Dermatol Res 2010; 302: 85–93. 2 Patroi I, Annesi G, Girolomoni G. Mid-dermal elastolysis: a clinical, histologic, and imunohistochemical study of 11 patients. J Am Acad Dermatol 2003; 48: 846–851. 3 Bannister MJ, Rubel DM, Kossard S. Mid-dermal elastophagocytosis presenting as a persistent reticulate erythema. Australas J Dermatol 2001; 42: 50–54. 4 Hillen U. Reticular erythema with focal mid-dermal elastophagocytosis (REMDE). J Dtsch Dermatol Ges 2008; 6: 857–859. 5 Martin LK, Kossard S, Murrell DF. Reticular variant of mid-dermal elastolysis. Am J Dermatopathol 2008; 30: 287–290.

A case of pleomorphic fibroma of the skin presenting as intradermal nodule.

To the Editor: Pleomorphic fibroma of the skin (PFS) is a rare cutaneous fibrous tumor first described by Kamino et al in 1989. PFS typically presents as a flesh-colored, dome-shaped papule on the trunk or extremities of middle-aged to older adults. Rarely, PFS may appear at other sites such as the face and subungual area. Histologically, the lesion is sparsely cellular and composed predominantly of thick, haphazardly arranged collagen. Characteristic features are the presence of scattered, spindle-shaped, or stellate cells, including multinucleated giant cells with large pleomorphic, hyperchromatic nuclei and a small nucleolus. The lesion is almost always 0.5–2.0 cm in diameter and is often mistaken clinically for a nevus, neurofibroma, or hemangioma. Here, we report a case of PFS in an otherwise healthy 50-year-old Japanese man manifesting as a painless, walnut-sized, intradermal nodule on the back that was clinically similar to an epidermal cyst. A 50-year-old Japanese man was referred to our department with a longstanding history of an asymptomatic subcutaneous lump on his back, which had gradually enlarged over a period of approximately 8 years without any history of preceding injury to the area. He was otherwise healthy with an unremarkable medical history. On physical examination, the mass was 3 cm in diameter, slightly raised, mobile, elastic hard, and associated with slight erythema of the overlying skin (Fig. 1A). Ultrasonography revealed an isoechoic to low echoic mass, 25.2 · 27.3 · 11.9 mm in size, with posterior acoustic enhancement and lateral shadowing (Fig. 1B). The results of routine laboratory investigations were within normal limits. An initial diagnosis of an epidermal cyst was made, and the lesion was surgically removed under local anesthesia. Histopathological examination of the excised specimen showed a hypocellular lesion involving the reticular dermis and extending to the borders abut the subcutis (Fig. 2A). There was neither acanthosis nor hyperpigmentation of the overlying epidermis. The lesion was composed of haphazardly arranged, spindle-shaped cells with fusiform nuclei and eosinophilic cytoplasm, and stellate mononucleated cells with mild cytologic atypia in a collagenous stroma (Fig. 2B). Neither mitotic figures nor necrosis were noted. Immunohistochemistry revealed that the lesional cells expressed vimentin, smooth muscle actin, factor XIIIa, CD99, and CD34 (Fig. 2C) but was negative for S100 protein and desmin. From these findings, we diagnosed the lesion as PFS. No recurrence has been noted at 1-year follow-up. PFS is a rare fibrous tumor characterized by nuclear atypia but with a benign clinical course. Less than 20 reports exist in the medical literature. Immunohistochemically, the tumor cells stain diffusely for vimentin, and a variable number of cells are positive for smooth muscle actin and CD34, suggesting either a myofibroblastic or dermal dendritic cell origin. Immunoreactivities for S100 protein, desmin, and cytokeratins are negative. Some PFSs also have features of sclerotic fibromas. Indeed, some investigators postulate that PFS is actually a variant of sclerotic fibroma. Alternatively, other researchers have labeled these tumors as pleomorphic sclerotic fibromas. In our case, thickened and homogenized eosinophilic collagen bundles arranged in a laminated fashion (whorled pattern) with intervening prominent clefts were absent; therefore, we diagnosed the lesion as PFS rather than sclerotic or pleomorphic sclerotic fibroma. PFS may clinically resemble a nevus, neurofibroma, hemangioma, fibrokeratoma, or fibroepithelial polyp. The initial clinical diagnosis in our case was an epidermal cyst as the lesion was mobile, elastic hard, and slightly raised, and ultrasonography revealed an isoechoic to low echoic mass with posterior acoustic enhancement and lateral shadowing. We think that our case of PFS is unusual as it was an intradermal nodule and was relatively large in size compared with previously reported cases. Histopathological findings of PFS may lead to the inclusion of malignancy in the differential diagnosis. Careful histological examination will readily distinguish PFS from the more cellular tumors of malignant fibrous histiocytoma and atypical fibroxanthoma, which contain cells arranged in a fascicular to storiform pattern with foamy cytoplasm and frequent (sometimes atypical) mitotic figures. In our case, cytologic atypia was present,

Cutaneous metastases of prostatic small cell neuroendocrine carcinoma

An 86-year-old Japanese man was referred to our department with a history of indurated masses growing rapidly on the face over the preceding few weeks. Three years earlier, the patient had undergone transrectal ultrasonography (TRUS)-guided prostate needle biopsy and had been diagnosed with prostate cancer (well-differentiated adenocarcinoma with positivity for androgen receptor (AR), Gleason score: 3 + 4 = 7, T3aN0M0 stage C1). He had declined radical prostatectomy due to his advanced age, and [...]