Search

Keratoacanthoma (KA) is characterized by exoendophytic growth with a central keratin-filled crater, representing the crateriform architecture. We herein report five rare cases of KA without a central keratin-filled crater. These KA cases histopathologically showed that one or a few infundibular structures/isthmic lobules had their own open keratotic pores on the surface without a common merged keratotic plug/horn, clinically representing verrucous (keratotic) plaque/nodule, namely, "KA en plaque/nodule". KA rarely but on occasion does show verrucous plaque (or nodular) lesions without a central keratin-filled crater, as the notion that KA invariably shows crateriform architecture is nonsensical.

Keratoacanthoma (KA) is a distinct clinicopathological entity, but it is often confused with other crateriform tumors. This study re-examined the clinicopathological features of 380 crateriform epithelial tumors with a central keratin plug. Seventy-six tumors (20%) had histopathological features that differed from solitary KA and were more verruca-like, and we designated these lesions as crateriform verruca (CFV). We performed clinicopathological re-examination of these neoplasms with a crateriform architecture and epithelial lip-like structures similar to KA, which also displayed histopathological features reminiscent of verruca vulgaris, such as finger-like exophytic projections with hyperkeratosis and acanthosis, focal hypergranulosis and arborization. Clinical data on CFV were also summarized. The main histopathological differences from KA were that CFV showed proliferation of keratinocytes with a similar size and regular arrangement, and the base of CFV was well demarcated without endophytic growth. Interestingly, some CFV were partly composed of epithelial cells with large pink cytoplasm in the upper malpighian layer between papillomatous projections. Furthermore, areas of trichilemmal-like keratinization without formation of the granular layer were seen in some lesions. These types of CFV were hardly distinguishable from KA, unless it is recognized that CFV may contain trichilemmal keratinization-like areas accompanied by large epithelial cells with eosinophilic cytoplasm. We have proposed the term CFV for these verrucous neoplasms to differentiate them from KA.

Few cases of a true benign neoplasm with sebaceous mantle differentiation have been reported, and little is known about this tumor. Herein, we present a rare case of the neoplasm called sebaceous mantleoma, along with a comparison of the histology and immunoprofile with those of normal sebaceous mantles. A pedunculated polyp occurred on the scalp of a 51-year-old woman. Histopathologically, the tumor showed lobulated epithelial-mesenchymal units that were separated from the normal dermis by clefts. The lesion was composed of cords and columns of basaloid cells containing a few mature sebocytes, with a focal connection to infundibulocystic structures as well as dense fibrotic or fibromyxoid stroma. Immunohistochemically, androgen receptor, estrogen receptor, and CD117 were partially positive for the tumor, and CD8 (C8/144B) and epithelial membrane antigen were focally positive. Additionally, cytokeratin 20-positive Merkel cells were individually admixed in the tumor nests as well as in normal sebaceous mantles. This case report reveals the characteristic histology and immunoprofile of this problematic benign neoplasm and helps to understand this entity.

We herein report a patient who clinically presented with a yellowish, flat plaque that histopathologically showed a benign lesion mainly composed of intraepidermal basaloid nests with sebaceous differentiation. This lesion was considered to be fundamentally apocrine poroma (hidroacanthoma simplex type) with sebaceous differentiation. Nests composed of typical poroid cells were seen, and the results of immunostaining for lumican supported this diagnosis and excluded the possibility of clonal seborrheic keratosis. The sebaceous differentiation in apocrine poromas mostly occurs in Pinkus type lesions, and is usually seen in only part of the lesions, as solitary, mature sebocytes within the poroma nests. However, our apocrine poroma case was unique not only in that sebaceous differentiation occurred in the hidroacanthoma simplex type, but also in that it was observed extensively (approximately 60% of the nests). We therefore called this lesion an 'intraepidermal benign sebaceous neoplasm'. Although it may be hard to differentiate sebaceous germinative cells (seen in sebaceoma) from poroid cells, in this case, some poroma nests could be judged to neighbor or contain the sebaceoma-like areas. Therefore, the presented apocrine poroma was considered to have some features of (intraepidermal and dermal) sebaceoma.

Bowen's disease (BD)/carcinoma is a type of squamous cell carcinoma of the skin, however, the possibility of adnexal differentiation (the development of sebaceous carcinoma or porocarcinoma) occurring in BD/carcinoma has been suggested. We herein describe a case of BD with superficial invasive carcinoma, which showed a clear cell focus, demonstrating tricholemmal differentiation. This clear cell focus showed the following findings: primarily composed of clear cells, somewhat columnar clear cells aligned in a palisade along a discernible basement membrane, tricholemmal keratinization and glycogen contained within the cells. In addition, the immunohistochemical profile in this clear cell focus, namely, negative staining for cytokeratin (CK)1 and positive staining for CK17 and calretinin in the inner cells of the neoplastic lobule, corresponded to that of the outer root sheath cells. This case suggested that adnexal differentiation can rarely occur within true BD/carcinoma, although adnexal carcinomas are commonly associated with a simple bowenoid change.

There is some confusion regarding the classification of keratoacanthoma (KA) and related lesions that have crateriform architecture. We examined the clinical courses of 66 KA lesions and related lesions after a partial biopsy to clarify the nosological concept of KA. We histopathologically classified these lesions into five types: (i) KA at various stages (53 lesions); (ii) KA-like squamous cell carcinoma (SCC) (3 lesions); (iii) KA with malignant transformation (3 lesions); (iv) infundibular SCC (5 lesions); and (v) crateriform SCC arising from solar keratosis (2 lesions). We analyzed the clinical course in each group. The regression rate of KA was 98.1% and that of KA-like SCC/KA with malignant transformation was 33.3%. No regression was observed in either infundibular SCC or crateriform SCC arising from solar keratosis. Thus, KA is a distinct entity that should be distinguished from other types of SCC with crateriform architecture based on the high frequency of regression. The regression rate of 33.3% in KA-like SCC/KA with malignant transformation indicated that KA lesions with an SCC component still have the potential for regression. However, this result also indicated that KA is biologically unstable, and some KA tend to evolve into conventional SCC with a gradual loss of the capacity for the spontaneous regression. Infundibular SCC and crateriform SCC arising from solar keratosis are fundamentally different from KA, not only according to the histopathological findings but also based on the biological properties.

We herein report two cases of cystic trichoblastoma with an immunohistochemical study. The histopathological findings in these cases included new information, namely, their being composed of two and three cysts, the cystic components had features of a steatocystoma and a hybrid cyst in one case, and there were projections of an aggregation of trichoblastoma, as well as papillary projections of follicular germinative cells, from the cyst walls. The follicular germinative cells observed in the papillary projections and in the aggregations of trichoblastoma expressed cytokeratin-15 (clone C8/144B) and PHLDA1, markers of follicular stem cells. Cystic trichoblastoma is a unique type of trichoblastoma, which originates from the cyst walls of an infundibular cyst (usually) or steatocystoma/hybrid cyst (rarely). In some cases, a trichoblastic infundibular cyst is considered to be a minor form (or possibly a primitive stage) of cystic trichoblastoma.

We herein report the natural course of an early/proliferative stage keratoacanthoma (KA) with infiltrating islands of cytological malignancy (case 1) and a squamous cell carcinoma (SCC) with a KA-like component (case 2), which were observed until their complete regression. The presented case 1 suggests that one of the histopathological forms of KA includes this unusual, infiltrating, non-crateriform architecture, and also indicates the possibility of complete remission in the KA associated with infiltrating islands of cytological malignancy. In the presented case 2, the peripherally-associated KA-like focus was histopathologically considered to be either a remnant of KA focus or verrucous keratosis (hyperplasia). Therefore, the complete spontaneous regression of case 2 suggests that SCC arising in KA still has the potential of spontaneous regression, or that an extremely rare event, namely, the spontaneous regression of (traditional) SCC occurred in the present case.

Background Although the precise etiology of keratoacanthoma (KA) is unknown, KA is generally assumed to differentiate toward hair follicles based on previous studies of experimental carcinogenesis. Methods We performed a comprehensive immunohistochemical study of various follicular markers in all stages of KA. A total of 67 tumors, including 16 early or proliferative stage lesions, 43 well-developed stage lesions, five regressing stage lesions and three regressed stage lesions, were subjected to the analysis. Results CK15 (clone C8/144B), CK19 and CD34 were not expressed at any stage. CK1, CK10, CK16, CK17, CK15 (clone LHK15) and calretinin showed dynamic changes in their expression in KA depending on the stage. Conclusions KA is a follicular neoplasm with infundibular/isthmic (upper segmental region of hair follicles) differentiation. It is considered that early or proliferative stage tumors show keratin-filled invaginations with infundibular differentiation and gradual isthmic differentiation. Well-developed examples of KA generally show isthmic differentiation in the whole lesions. The regressed stage KAs lose the features of this type of follicular differentiation and show epidermal characteristics. No expression of CK15 (clone C8/144B) was observed in KAs, although this finding is insufficient to completely rule out the correlation between the regression of KA and the hair follicle cycle.

We present a rare case of Merkel cell carcinoma (MCC) with heterologous differentiation. The patient was an 86-year-old female patient with MCC who presented with a forearm skin tumor and left axillary lymph node swelling. Histopathologically, the malignant components of the primary and metastatic lesions showed the intermingled features of triphasic phenotype differentiation, which had distinct cell populations; MCC, sweat gland carcinoma (SGC) and malignant poorly differentiated spindle cells with myogenic differentiation were immunohistochemically showed. Moreover, an electron microscopic observation of the tumor cells revealed intracytoplasmic canaliculi and junctional structures that indicated ductal differentiation. To our knowledge, this is the first case of MCC admixed with SGC and sarcomatous components in both the primary and metastatic lesions. An immunohistochemical study, using several stem cell markers, indicated that the MCC arose from pluripotent epidermal stem cells.

Some authors have reported that the secondary hair follicles in trichofolliculomas (TF) undergo regressive changes and are subsequently replaced by the developed sebaceous elements, and that folliculosebaceous cystic hamartoma (FSCH) is a TF at a very late stage. In the present study, we revaluated the histopathological features of 40 TF lesions, focusing on their chronological changes. The results of the present study indicate that while the secondary follicles in the TF exhibited the hair cycle, the normal hair cycle was out of control, and tertiary hair follicles randomly developed from the involuting secondary follicles. The repeated development of hair follicles in this disordered hair cycle caused the development of chains of several continuous hair follicles in late-stage TF. In the TF lesions, no features indicating the replacement of the regressing secondary hair follicles by any sebaceous elements were observed, thereby suggesting that FSCH is not a very-late-stage TF.

Summary Background. The diagnostic criteria for tricholemmal carcinoma remain controversial, and even the existence of tricholemmal carcinoma has been the subject of debate. Follicular (infundibular) squamous cell carcinoma (SCC) is a distinctive subset of SCC, which develops solely with folliculocentricity, and displays the features of conventional SCC without tricholemmal differentiation. Aim. To examine the existence of pure folliculocentric SCCs showing tricholemmal differentiation, that is, tricholemmal carcinoma. Methods. In total, 812 SCCs were examined, and those meeting the following diagnostic criteria were selected: (i) pure folliculocentricity without any associated Bowen's disease or actinic keratosis; (ii) composition primarily of lightly eosinophilic cells or clear cells containing glycogen; (iii) columnar lightly eosinophilic or clear cells aligned in a palisade along a discernible basement membrane; (iv) tricholemmal keratinization; (v) glycogen contained within the pale/clear cells; and (vi) cytological atypia and or infiltrative growth. We also evaluated whether the immunohistochemical profile [cytokeratin (CK)1, CK10, CK17, CD34 and D2–40] seen in normal hair follicles was retained in the selected lesions. Results. Only two lesions met the criteria. The immunohistochemical profile of the normal outer root sheath cells was generally retained in these lesions, except for CD34. Conclusions. Tricholemmal carcinoma is a rare occurrence, but it does exist, and at least one type of tricholemmal carcinoma is considered to be related to follicular (infundibular) SCC.

We herein report a patient with erythema induratum/nodular vasculitis (EI/NV) associated with Crohn's disease (CD), which is considered to be a rare type of metastatic CD. A 54-year-old woman, who had a history of CD, presented with erythematous nodules on her legs. The histopathological features of the skin biopsy revealed a granulomatous, mixed septal and lobular panniculitis, which was characterized by many discrete epithelioid cell granulomas (necrobiotic/necrotizing-type and sarcoidal type), necrosis of the adipocytes, and granulomatous phlebitis in the muscular wall of a subcutaneous vein. A review of the pertinent literature and the presented case suggested the following: (1) panniculitis associated with CD may be either an erythema nodosum type or an EI/NV type; (2) so far, the reported cases of metastatic CD or granulomatous vasculitis in CD rarely presented with granulomatous panniculitis without dermal involvement, and most cases showed histopathological features that were similar to or indistinguishable from those of EI/NV; and (3) the finding of granulomatous vasculitis (especially the presence of discrete epithelioid cell granulomas involving the veins or venules) may be a characteristic feature of EI/NV associated with CD, in contrast to the finding of acute vasculitis, which is typically present in patients with EI/NV due to causative factors other than CD.

The histopathological features of erythema nodosum-like lesions remain controversial with regard to whether they resemble those of conventional erythema nodosum. We reviewed the clinicopathological features of erythema nodosum-like lesions in 26 patients with Behçet's disease and evaluated the clinical characteristics of Behçet's disease in these patients. The results suggest that: (i) the clinico-pathological features of 27% of the erythema nodosum-like lesions in Behçet's disease are indistinguishable from those of conventional erythema nodosum; (ii) the other 73% of the erythema nodosum-like lesions are histopathologically characterized by the presence of vasculitis (venulitis or phlebitis); (iii) the clinical features of erythema nodosum-like lesions with vasculitis show heterogeneity; (iv) the presence of the erythema nodosum type lesion may be an indicator of the mildness of Behçet's disease; and (v) the presence of severe vasculitis, especially phlebitis, in erythema nodosum-like lesions may be an indicator of the involvement of the gastrointestinal tract in Behçet's disease.

Basal cell carcinoma (BCC) is the most common malignant cutaneous neoplasm, however, there have been few studies on BCC with a "rippled pattern" so far. We reviewed the 650 BCC specimens from the archives of our institution, and only one example of BCC with a rippled pattern was found. We herein report the histopathological characteristics of this case. Within the lesion, which showed the typical histopathological features of nodular BCC, there was a noticeable area composed of 10-15 basaloid aggregations, which showed the rippled pattern. The rippled pattern was characterized by alternating bands of epithelial cords of spindle-shaped basaloid cells and mucinous spaces. Characteristically, around the rippled-pattern area, neoplastic aggregations with a mucinous reticulated or cystic pattern (pseudo-tubular structures), and many cord-like structures were seen. A review of the published work and the present case suggested that the histopathological characteristics of rippled-pattern BCC are: (i) a nodular type of BCC; (ii) considerably rare; (iii) have frequent intervention by mucinous spaces between the epithelial cords; and (iv) no apparent divergent differentiation with folliculosebaceous-apocrine lineage. The last three characteristics contrasted with those of the rippled-pattern sebaceoma/trichoblastoma. However, neoplastic germinative cells in rippled-pattern BCC may naturally form cord-like structures in a manner similar to rippled-pattern sebaceoma/trichoblastoma.

Background: There has recently been controversy regarding whether clone My10 is superior to clone QBEND-10 for labeling cells of tricholemmal lineage. Moreover, there have been no previous reports on the CD34 expression in human vellus hair follicles. Methods: We performed a comprehensive study of the CD34 expression in human terminal and vellus hair follicles and in 10 tricholemmomas using both the QBEND-10 and the My10 clones. We also performed two different procedures of immunostaining, which included the using of the standard avidin-biotin-peroxidase (ABC) complex system and the Envision system. Results: The most sensitive marker of CD34 for normal human hair follicles and tricholemmomas is QBEND-10 using the ABC system. The degree and strength of the CD34 positive staining mainly depended on the method being used (whether it was the ABC system or the Envision system) rather than the clone. CD34 staining was rarely (20–30%) seen in the anagen and catagen vellus hair follicles, and could only be seen by the QBEND-10 clone using the ABC system. CD34 expression in the tricholemmomas represented either a diffuse or peripheral pattern. Conclusions: CD34 may not be a tricholemmal lineage-specific antigen, but may be related to certain functions of the cells. Misago N, Toda S, Narisawa Y. CD34 expression in human hair follicles and tricholemmoma: a comprehensive study.

29歳，女性。右臀部に結節が出現し，妊娠に気付いた頃より徐々に増大した。妊娠8週頃に流産し，その後，結節は縮小傾向であった。近医皮膚科を受診し，局所麻酔下に切除され，病理組織学的に悪性黒色腫のため，当科紹介となった。明らかな遠隔転移なく，センチネルリンパ節生検は陰性であり，pT4aN0M0 : Stage II B と診断した。原発巣の拡大切除術を行い，DAV-Feron 療法を開始後まもなく，右鼠径部のリンパ節転移を認めた。リンパ節郭清を行い DAV-Feron 療法を5クール目まで行ったが，初診の2年後に多発転移を認め，永眠された。自験例は，妊娠中に増大し流産後に縮小傾向となった悪性黒色腫であり，妊娠と悪性黒色腫の関与を伺わせ，文献的考察を加え報告した。

生後1日，男児。出生時より顔面と前胸部に環状の紅斑が多発していた。母子ともに抗核抗体，抗SSA抗体・抗SS-B抗体が非常に高値であり，新生児エリテマトーデス(NLE)と診断した。先天性房室ブロックの合併はなかった。経過中，潰瘍化するほどの激しい皮膚症状を呈したが，生後3ヵ月頃より患児の自己抗体価は低下し始め，生後8ヵ月で紅斑は消退した。

症例は55歳，女性。左大腿内側に青色調の皮下硬結を認め，MRIで脂肪織炎や外傷性変化が疑われた。切除時に白色索状物が摘出され，病理組織学的所見よりマンソン孤虫症と診断した。全身検索で他臓器に病変は認めなかった。切除後も硬結が残存するためプラジカンテル内服を行い，硬結は速やかに消失した。治療効果判定のため測定した抗マンソン孤虫-IgG抗体は3ヵ月後に低下した。自験例のように一定期間，臨床的変化がない単発の皮下結節では通常は皮膚良性腫瘍をまず疑い，マンソン孤虫症などの寄生虫症を考えることは困難なため文献的考察を加え報告する。

A 51-year-old Japanese woman underwent subtotal colectomy for ulcerative colitis 5 years before her first visit to our hospital, and her symptoms stabilized. She presented with a 2-month history of proliferative, pustular lesions on her face, scalp, and gingival and anal mucosae. Histological examination showed features similar to those of pemphigus vegetans. However, the results of immunofluorescence studies, immunoblot analysis and enzyme-linked immunosorbent assay for pemphigus were negative, and colonoscopy revealed a relapse of ulcerative colitis in the remaining rectal mucosa, so a diagnosis of pyodermatitis-pyostomatitis vegetans was made. This is the first report of mucocutaneous lesions that developed with a relapse of ulcerative colitis in the remaining rectum after subtotal colectomy. Moreover, a close correlation was found between the condition of bowel inflammation and that of mucocutaneous lesions.

The histogenesis of folliculosebaceous cystic hamartoma (FSCH), including the origin of the frequently associated adipocytes and other mesenchymal components, remains unclear. There are controversial problems regarding FSCH, such as the relationship between FSCH and trichofolliculoma (TF), and the exact concept of sebaceous TF. Fourteen FSCHs and 1 sebaceous TF were revaluated for the histopathology and studied for immunohistochemical profile of various cytokeratins, hair follicular stem cell markers, and others. The nestin expression was partly upregulated in the sebaceous duct structures and the proliferating spindle cells in the surrounding connective tissue in some lesions. S-100 protein staining clarified the presence of lipogenesis in these nestin-expressed lesions, and the nestin-positive spindle cells were also seen around the immature adipocytes. Some FSCHs showed the focal follicular differentiation, where no signs of catagen or telogen stage were seen. One peculiar case showed both FSCH and TF features equally. The possibility that the adipocytes and other mesenchymal components in FSCHs originated from the nestin-positive multipotent stem cells was suggested. It is not convincing that FSCH and TF represent a chronological change in the spectrum of the same condition. Each FSCH and TF is therefore considered to be a distinctive entity. They may develop under a similar pathogenesis differing from each other in the direction of fundamental differentiation. In contrast to the TF lesions, the unusual upregulation of nestin expression is occasionally seen in FSCH lesions, including their stromas, which may thus result in the production of various kinds of mesenchymal components in FSCHs.

The air-liquid interface (ALI) is a common microenvironment of the skin, but it is unknown whether the ALI affects melanoma cell behaviors. Using a collagen gel invasion assay, immunohistochemistry, and Western blots, here we show that melanoma cell proliferation in cultures with an ALI is higher than melanoma cell proliferation in submerged cultures. Bromodeoxyuridine (BrdU) uptake, an indicator of cell proliferation, of melanoma cells at the ALI was about 3 times that of submerged cells, while ALI and submerged melanoma cells had similar levels of single-stranded DNA (a marker of apoptosis). The ALI enhanced the expression of Raf-1, MEK-1 and pERK-1/2 components of the mitogen-activated protein kinase (MAPK) cascade, in cells more than the submerged condition did. The increases in BrdU uptake and pERK-1/2 expression promoted by ALI was abolished by the MEK inhibitor, PD-98059. ALI-treated and submerged melanoma cells did not infiltrate into the collagen gel, and they showed no significant difference in the expression of the invasion- and motility-related molecules, matrix metalloproteinase-1 and -9, laminin 5, and filamin A. Our data indicate that the ALI, a skin microenvironment, accelerates the growth, but not the apoptosis or invasion, of melanoma cells through MAPK activation.

Few investigations on the histopathology of trichofolliculoma (TF) have so far included an immunohistochemical study. To seek new insight into TF with a revaluation of the histopathological features and an investigation of the immunohistochemical profile, 14 TFs were revaluated for the histopathology and the immunohistochemical profile of various cytokeratins (CKs), hair follicle stem cell markers, and others. The CK15 expression was upregulated in the basal cells from the primary cystic structures beyond to secondary follicles without expression of CK19. CK16 and CK17 were positive in the suprabasal cells of the primary cystic structures and the immature secondary hair follicles. No exact isthmus/bulge region was seen in the anagen secondary hair follicles, and newly developed (tertiary) hair follicles arose randomly from the involuting secondary follicles. Ber EP4 expression was generally weakened in the secondary or tertiary hair germ-like structures. The size of secondary hair follicles varied from vellus hair follicles to terminal hair follicles, even though no lesions located on the regions where the terminal hairs develop were included in this study. S-100 protein-positive wavy spindle cells were accidentally found in the surrounding connective tissue of the secondary follicles in 2 TF lesions. TFs were characterized by the proliferation of abnormal CK15-positive hair follicle stem cells, which basically differentiated toward the outer root sheath and attempting to make hair but losing the proper differentiation. The control of the size of the anagen hair follicles and the regular hair cycle were also disordered.

Summary Background Merkel cells (MCs) exist in the epidermal basal layer, in contact with keratinocytes. This direct contact seems critical for maintaining MCs in vitro. Objectives To estimate the effects of nerve cells on the maintenance of MCs within epidermal sheets in a new organotypic culture system of MCs. Methods We developed a new organotypic culture system of MCs, using MC-containing epidermal sheets embedded in collagen gel. To estimate the effects of nerve cells on the maintenance of MCs within the epidermal sheets, we cocultured nerve cells and MC-containing epidermal sheets. In these culture assemblies, cellular behaviour was analysed by histochemistry, immunohistochemistry, electron microscopy and enzyme-linked immunosorbent assay. Results This culture, even in the absence of neurotrophin (NT)-3 and nerve growth factor (NGF) (which are crucial for MC biology), retained cytokeratin (CK)-20-positive and neuroendocrine granule-containing MCs within the sheets for over 2 weeks. Coculture of MCs with PC-12 nerve cells significantly increased the number of MCs within the epidermal sheets, and the keratinocytes had almost identical expression levels of CK1, CK10, CK14 and the progenitor marker p63 to those produced by keratinocytes in vivo. Uptake of the growth marker bromodeoxyuridine by MCs and levels of NT-3 and NGF in the culture supernatants were undetectable in this system, regardless of the presence or absence of PC-12. Conclusions The data suggest, first, that direct contact between MCs and keratinocytes may be critical for retaining MCs in vitro; second, that nerve cell-affected maintenance of keratinocyte differentiation, but not NT-3 and NGF, may contribute to MC maintenance; and third, that MCs are not able to grow, at least in our system. Our method would be useful for studying MC biology.

Palisaded neutrophilic granulomatous dermatitis (PNGD) is a rare dermatologic condition which shows various clinical and histopathological features. Although the PNGD lesions have been suggested to begin as leukocytoclastic vasculitis (LCV), there is still insufficient clinicopathological information in the reported cases of PNGD in acute stage with LCV. The relationship between PNGD and interstitial granumatous dermatis (IGD) also remains unclear. This report presents the case of a 60-year-old female patient with multiple erythematous nodules on the extremities. She had no underlying systemic disease detected to date, although transient, abnormal liver function tests were seen. The histopathological examination of an erythematous nodule revealed the features of PNGD in the acute stage. The patient presented the characteristic features of LCV including palisaded granulomatous pattern, and the interstitial granulomatous pattern was seen together, suggesting that PNGD with LCV can show an interstitial granulomatous pattern. The present case also suggested that PNGD in the acute stage with LCV tends to clinically manifest as erythematous nodules on the extremities and histopathologically shows a remarkable papillary edema and an extensive fibrin deposition in and around the vessel wall. PNGD may be associated with transient liver dysfunction.

62歳，男性。初診の数日前より39℃の発熱と皮疹を認め，近医で治療を受けるも改善しないため当科を受診した。全身に爪甲大の淡い紅斑，肝障害，後頚部の刺し口と思われる皮疹，発熱などの特徴的な臨床像よりツツガムシ病と診断した。塩酸ミノサイクリンの点滴を開始し紅斑は急速に退色したものの，発熱は持続し肝障害も増悪した。塩酸ミノサイクリンによる副作用と考え，治療薬を変更せざるをえなかった。一般的にクロラムフェニコールも有効とされるが，直ちに薬剤を入手することができず，対応に苦慮することとなった。アジスロマイシンに変更したところ，解熱し肝機能障害も軽快した。またクロラムフェニコールを併用した。その後もツツガムシ病の再燃を認めなかった。

71歳，女性。1週間前より左臀部の紅斑・腫脹・疼痛が出現した。初診時，肛門左側から左臀部にかけて，びまん性の紅斑・腫脹・熱感を認めた。緊急手術を施行したところ，多量の排膿とともに鋭利な異物が発見された。異物は組織学的所見と形状から，魚骨と判断した。痔核や痔瘻は認められず，臀部慢性膿皮症などの所見もなく，膿瘍腔から魚骨が摘出されたことから，魚骨が肛門を穿通して皮下に迷入したことにより発症した肛門周囲膿瘍と診断した。魚骨の穿孔・穿通による肛門周囲膿瘍は，本邦において自験例を含め12例が報告されている。突然の肛門周囲膿瘍を見た場合には，稀ではあるが魚骨の穿孔や穿通による膿瘍形成も念頭におく必要があると考える。

Adequate clinical data and a sufficient workup, in addition to the histopathological findings, are frequently required to make a correct diagnosis of granulomatous dermatitis/panniculitis. These lesions with an unexpected etiology may include delayed hypersensitivity granulomatous reactions to various factors, such as metals or marine animal injuries. A 50-year-old male presented with multiple subcutaneous nodules on his right forearm 1 month following an octopus bite at his right wrist. After the disappearance of these lesions, which responded well to low-dose oral prednisone, another type of skin lesion characterized by small, numerous papules reappeared on his right forearm. Histopathologically, a specimen from a subcutaneous nodule showed mostly lobular granulomatous panniculitis, which showed an extensive diffuse infiltrate composed of numerous multinucleated giant cells and epithelioid cells intermingling with lymphocytes and eosinophils. A specimen from a papule that subsequently developed disclosed a diffuse granulomatous dermatitis composed of similar cells and also showed granuloma annulare-like features. This case is considered to be a delayed reaction after an octopus bite showing an unusual giant cell-rich granulomatous dermatitis/panniculitis. Octopus bites should therefore be included among the marine animal injuries, which cause a delayed-type reaction with granulomatous dermatitis/panniculitis.

Making a differential diagnosis to distinguish dermatofibrosarcoma protuberans (DFSP) from dermatofibroma (DF) is occasionally difficult. In those instances, CD34 and factor XIIIa have been used as valuable differential markers. The histogenesis of DFSP, however, remains uncertain and controversial, although it is generally thought to be a neuromesenchymal neoplasm. Nestin is an intermediate filament protein that was first observed in neuroectodermal stem cells. We investigated the expression of nestin in order to distinguish between DFSP and DF in combination with the use of conventional markers, CD34 and factor XIIIa. The nestin expression was investigated in tissue specimens from 16 DFSP cases and 30 DF cases. The expression of other differential markers such as CD34, factor XIIIa, CD163 and CD10 was also observed in these samples. Fifteen (94%) of 16 cases of DFSP showed the expression of nestin, whereas only four (13%) of 30 cases of DF showed the expression of nestin. Most of the DFSP cases showed a diffuse positive reaction in more than half of the tumor cells. In contrast, DF cases with nestin expression showed a partial positive reaction. Nestin is considered to be a useful and additional marker in combination with CD34, factor XIIIa and CD163 in order to distinguish between DFSP and DF. The frequent expression of nestin in DFSP may therefore indicate that DFSP is derived from putative, multipotent neuromesenchymal cells.

症例1は88歳の女性。2年前に右下腿前面の紅色結節を自覚し，徐々に結節は増大した。右下腿前面に7×6cm，弾性軟の皮下腫瘤を認めた。皮膚生検を行い，組織学的にmalignant fibrous histiocytomaと考えた。腫瘍切除術を行い，HE染色，免疫染色，電子顕微鏡検査の所見から，皮膚平滑筋肉腫の皮下型と診断した。半年後に局所再発を認め，下肢切断術を行った。症例2は79歳の女性。5∼6年前，右下腿前面の結節を自覚し，徐々に増大した。8×6cm，弾性軟の皮下腫瘤を認めた。皮膚生検を行い，組織学的に皮膚平滑筋肉腫の皮下型と診断した。右脛骨，肝，肺への転移を認めた。2例とも，近医外科を受診し問題ないと言われ放置し増大した症例である。早期診断のための皮膚生検が必要であり，医師の責任の重さを感じた。

We herein report an unusual case of apocrine carcinoma on the forehead. The lesion was formed by the anastomosis of numerous tubular structures with widespread decapitation secretion, thus demonstrating apocrine differentiation. However, we observed some unusual histopathologic features that differed from those found in typical examples of apocrine ductal carcinoma, namely: 1) a relatively well-circumscribed lesion in the dermis, and 2) nodular or solid aggregations composed of basaloid cells. We believe the present case is an apocrine ductal carcinoma, although it has a nodular appearance and basaloid cells. Otherwise, it could be a hitherto undescribed variant of apocrine carcinoma. This apocrine carcinoma on the forehead may have originated from either pluripotential cells or from apocrine glands at an unusual site.

症例は66歳の男性。露光部を中心とした著明な色素沈着を主訴に来院した。UVBの最小紅斑量の低下を認め，慢性光線性皮膚炎として治療を開始したところ，その経過中にゴットロン徴候や筋力低下，関節痛が出現した。種々の検査結果や皮膚生検の病理組織学的所見をあわせ，皮膚筋炎と診断した。さらに全身検索により原発性肺癌と肝転移を疑う病変および間質性肺炎の合併を認めた。治療としてプレドニゾロンの内服を開始したが，皮膚症状，筋症状に改善は認めず，間質性肺炎はわずかに改善したもののその後増悪し，間質性肺炎からの呼吸不全により死亡に至った。光線過敏症や著明な色素沈着を伴う皮膚筋炎は，悪性腫瘍の合併が高率であるため注意が必要である。

36歳，男性。22歳頃，左側頭部の皮下結節を自覚し，以後，結節は徐々に増大した。初診時，左側頭部に径4cm の皮下腫瘤を認め，球状で弾性硬，圧痛は伴わず下床との可動性は良好であった。局所麻酔下に摘出し，頭蓋骨との癒着はなかった。病理組織検査では腫瘍細胞が，cell nestあるいは渦巻き状の構造を示して増殖していた。核は類円形で空胞状核を有し，細胞境界は不明瞭であった。免疫染色にてvimentin(＋)，S-100 protein(＋)，estrogen receptor(＋)，progesterone receptor(＋)であり髄膜腫と診断した。頭部MRIにて頭蓋内，頭蓋骨内に腫瘤影は認めず，骨欠損や骨浸潤も認めなかったことから，皮膚原発の髄膜腫と診断した。皮膚原発の髄膜腫は稀であり，さらに側頭部に生じたのは本邦の報告で初めてであった。

70歳，男性。初診の4ヵ月前より背部にそう痒を伴う紅斑が出現した。膝関節，手背にも紅斑が拡大し，下肢の筋力低下も伴うようになった。臨床所見及び病理組織学的所見より皮膚筋炎と診断した。初診時血液検査にて汎血球減少と異型リンパ球を認めたため，造血器悪性腫瘍を疑い骨髄穿刺を施行し，急性骨髄性白血病と診断した。皮膚筋炎に悪性腫瘍を合併することが多いことは知られているが，急性骨髄性白血病を合併する症例は非常に稀であり，国内外併せて自験例を含め3例のみであった。悪性腫瘍を合併した皮膚筋炎について若干の考察を加えた。

BRAF gene mutations have been observed in 30–50 % of malignant melanoma patients. Recent development of therapeutic intervention using BRAF inhibitors requires an accurate and rapid detection system for BRAF mutations. In addition, the clinical characteristics of the melanoma associated with BRAF mutations in Japanese patients have not been investigated on a large scale evaluation. We recently established quenching probe system (QP) for detection of an activating BRAF mutation, V600E and evaluated 113 melanoma samples diagnosed in Saga University Hospital from 1982 to 2011. The QP system includes fully automated genotyping, based on analysis of the probe DNA melting curve, which binds the target mutated site using a fluorescent guanine quenched probe. BRAF mutations were detected in 54 of 115 (47 %) including 51 of V600E and 3 of V600 K in Japanese melanoma cases. Among clinical subtypes of melanoma, nodular melanoma showed high frequency (12 of 15; 80 %) of mutation followed by superficial spreading melanoma (13 of 26; 50 %). The QP system is a simple and sensitive method to determine BRAF V600E mutation, and will be useful tool for patient-oriented therapy with BRAF inhibitors. Introduction

We describe a unique case of Merkel cell carcinoma (MCC) with a heterogeneous differentiation exhibiting distinct triphasic phenotypic differentiation features: small cells typical of MCC, sweat gland carcinoma (sweat gland Ca.) with possible decapitation secretion, and spindle cell carcinoma (spindle cell Ca.). The patient was an 84-year-old Japanese woman. We evaluated the present case immunohistochemically with various antibodies. The histological features showed a gradual transition from MCC to sweat gland Ca. and spindle cell Ca. For clarifying the histogenesis, immunophenotypic analysis of the 3 different components of the carcinoma was performed using hair follicle stem cell markers (eg, CK15, CK19, and CD200) that have been identified as biomarkers of human bulge cells. The triphasic components immunohistochemically shared the characteristic feature of CK19 and CD200 expression. We posit that the MCC arose from hair follicle stem cells residing within the bulge area where Merkel cells are preferentially situated. Based on our findings, we recommend adding this rare neoplasm to the expanding morphological spectrum of MCC.

Background: Recent studies have demonstrated that the cytokeratin 15 (CK15)-positive stem cells located in the hair follicle bulge are also involved in sebaceous gland renewal. No previous studies have dealt with the CK15 expression in sebaceous neoplasms. Methods: We studied the CK15 expression in 30 sebaceous neoplasms including 10 sebaceomas (sebaceoma defined as a distinct benign neoplasm with sebaceous differentiation), 10 sebaceous neoplasms of Muir–Torre syndrome, and 10 sebaceous carcinomas, in addition to that in the mantles of normal hair follicles. Results: CK15 was positive in the undifferentiated sebocytes of the mantles. All 10 sebaceomas showed CK15 expression in the basaloid, germinative cells. Both sebaceous neoplasms in Muir–Torre syndrome and sebaceous carcinomas demonstrated negative or only a focal positive reaction, including the occasional aberrant expression in matured sebocytes, to CK15. Conclusions: CK15 may be a useful marker for stem cells with a sebaceous fate, and a constant CK15 expression in sebaceomas supported the hypothesis that sebaceoma is a benign neoplasm of sebaceous germinative cells in the mantles. The similar staining pattern of CK15 between sebaceous neoplasms in Muir–Torre syndrome and sebaceous carcinomas may be one piece of evidence supporting the hypothesis that most sebaceous neoplasms in Muir–Torre syndrome are low-grade sebaceous carcinomas.

Summary Background Hair discs are known to contain a large number of Merkel cells and are ideal for investigating Merkel cell biology. Hair follicles, which are important elements of hair discs, undergo unique cyclical morphological and biological changes. Objectives To define the relationships between the number and the morphology of Merkel cells within the hair disc in association with the hair cycle on rat back skin. Methods Merkel cells in hair discs were observed three-dimensionally using immunohistochemistry. Epidermal sheets were incubated with monoclonal murine antibody to CK20. As a result, Merkel cells in hair discs were clearly demonstrated as whole shapes and were counted under a light microscope. Results Merkel cells in hair discs increased during the early to middle phase of anagen and decreased during the middle phase of anagen to catagen and telogen in perinatal and postnatal rat back skin. We observed the morphological variation of Merkel cells in hair discs of rat back skin, and consequently divided them into two subtypes at the light microscopic level: the oval type and the dendritic type. The number of oval-type Merkel cells was not markedly affected by the hair cycle. In contrast, the number of dendritic-type Merkel cells markedly changed with the hair cycle. Conclusions This difference of the hair cycle dependency between oval and dendritic-type Merkel cells suggests some functional differences, such as a secretory function, related to the hair cycle.

87歳，女性。両側手掌，手背，足底に水疱が出現し，四肢に水疱が拡大したため当科紹介となった。膝関節周囲から大腿部，上腕にほぼ対称性に径0.5～1cmと小型の緊満性水疱を認めた。水疱部の病理組織では表皮下水疱を認め，周囲の真皮には好中球が主体で，好酸球，リンパ球などの炎症細胞浸潤がみられた。蛍光抗体直接法にて基底膜にIgG，C3の線状沈着を認めた。1M食塩水剥離皮膚を用いた蛍光抗体間接法ではIgGが真皮側に反応し，真皮抽出液を用いた免疫ブロット法にて200kDaタンパクと反応し，抗p200類天疱瘡と診断した。また，爪の白濁と肥厚を認め，疥癬の治療歴があったことから疥癬を疑った。爪下の角質から疥癬の虫体，虫卵を検出した。ステロイド投与および疥癬の治療にて水疱は速やかに改善した。抗p200類天疱瘡と共に疥癬との関連についても文献的考察を加えた。