Shin-ichi Ansai

Ber-EP4 is a useful marker for follicular germinative cell differentiation of cutaneous epithelial neoplasms.

Ber‐EP4 is a monoclonal antibody that recognizes 34‐kDa and 39‐kDa non‐covalently linked glycopolypeptides expressed by most human epithelial cells and carcinomas. In this study, we performed immunohistochemical staining of 31 cases of basal cell carcinoma (BCC); 20 cases of trichoblastoma (TB), including ten cases of nodular type, eight cases of cribriform type (trichoepithelioma) and two cases of columnar type (desmoplastic trichoepithelioma); 16 cases of actinic keratosis (AK); and 10 cases each of Bowen’s disease, poroma and seborrheic keratosis. Six cases of BCC and AK were co‐lesions of both neoplasms. In normal skin tissue, Ber‐EP4 reacted positively with the secretory portion of eccrine glands and follicular germinative cells at the lower end of catagen hairs. Neoplastic cells in 97% of cases with BCC reacted positively with Ber‐EP4 in at least 5% of neoplastic cells. Those in 90% with nodular type TB and 50% with trichoepithelioma also reacted positively in at least 5% of neoplastic cells. No cases of poroma, seborrheic keratosis, AK or Bowen’s disease were immunohistochemically positive for Ber‐EP4 in neoplastic cells. In all six cases with co‐lesions of BCC and AK, neoplastic cells of BCC reacted positively with Ber‐EP4 and those of AK were negative. Immunohistochemical examination using the Ber‐EP4 antibody is a useful tool for diagnosing neoplasms with follicular germinative differentiation, such as TB, TE or BCC, and for differentiating those from squamous cell carcinoma in situ, poroma or seborrheic keratosis.

Immunohistochemical findings of sebaceous carcinoma and sebaceoma: Retrieval of cytokeratin expression by a panel of anti-cytokeratin monoclonal antibodies

This study examined immunohistochemical findings of sebaceous carcinoma and sebaceoma. An immunohistochemical study using 13 anti‐cytokeratin (CK) antibodies (anti‐CK1, 5–8, 10 and 14–20) and 35 cases of sebaceous carcinoma (16 cases on ocular and 19 cases on extraocular regions) and 10 cases of sebaceoma (no cases arose on the eyelids) was performed. Overall, those in ocular lesions were almost the same as those for extraocular lesions in sebaceous carcinoma other than CK8. The findings in sebaceous carcinoma were almost equal to those of sebaceoma. Over 75% of cases with sebaceous carcinoma were positive with anti‐CK5 and anti‐CK14 antibodies and negative with anti‐CK1, CK10, CK15, CK17, CK18 and CK20 antibodies. Most cases (50–75%) of those were positive with CK7 and negative with CK6, CK16, CK19 and CK8. The sensitivity and specificity of immunohistochemical detection of sebaceous carcinoma using the panel of anti‐cytokeratin antibodies were lower than those of other antibodies. Immunohistochemical detection of cytokeratins in diagnosing sebaceous carcinoma should be considered to be ancillary to conventional microscopic findings and those of other antibodies.

Extraskeletal osteochondroma arising on the plantar region.

Extraskeletal osteochondroma is a variant of extraskeletal chondromas that are uncommon soft-tissue cartilaginous tumors. These tumors may undergo extensive enchondral ossification to form an extraskeletal osteochondroma. This report describes the case of a 39-year-old Japanese man with an extraskeletal osteochondroma arising on the plantar aspect of the foot.

Insulin-like growth factor 2 mRNA-binding protein-3 as a marker for distinguishing between cutaneous squamous cell carcinoma and keratoacanthoma

In the histopathological diagnosis of cutaneous tumors, the differential diagnosis of squamous cell carcinoma (SCC) with crateriform architecture and keratoacanthoma (KA) is often difficult so an accurate understanding of the biological features and the identification of reliable markers of SCC and KA are crucial issues. Insulin-like growth factor 2 mRNA-binding protein-3 (IGF2BP3, also known as IMP3) is thought of as a bona fide oncofetal protein, which is overexpressed and is involved in cell proliferation, migration, and invasion in several kinds of tumors. However, the role of IMP3 in cutaneous SCC and KA has not been well studied. Therefore, we focused on studying the biological functions of IMP3 in SCC and KA. In human skin SCC cell lines, HSC-1 and HSC-5, and the human keratinocyte cell line, HaCaT, IMP3 mRNA levels were significantly higher than that of normal human skin. The knockdown of IMP3 expression reduced the proliferation of HSC-1, and significantly reduced invasion by HSC-1 and HSC-5. In contrast, the knockdown of IMP3 did not significantly affect invasion by HaCaT cells. In immunohistochemical studies of SCC and KA tissues, the Ki-67 labeling index (LI) of the suprabasal cell layer was significantly higher in SCC, compared with KA tissues and the tumor-free margin (TFM) adjacent to SCC and KA. Most SCC tissues stained strongly positive for IMP3, but KA tissues and TFM were mostly negative for IMP3. The Ki-67 LI of the IMP3-positive group was significantly higher than that of the IMP3-negative group in the suprabasal cell layer of SCC. These results suggest that IMP3 plays an important role in proliferation and, more significantly, in the invasion of SCC, and may be a suitable marker for the histopathological diagnosis of SCC with a crateriform architecture and KA. Furthermore, IMP3 may potentially be a new therapeutic target for SCC.

Lumican as a novel marker for differential diagnosis of Bowen disease and actinic keratosis.

Abstract:Lumican, a member of the small leucine-rich proteoglycan family, regulates the assembly and diameter of collagen fibers in the extracellular matrix of various tissues. Lumican expression correlates with pathological conditions, including skin fragility, corneal opacification, and corneal and cardiac wound healing. Lumican is overexpressed in tumor cells, including in the breast, colorectal, neuroendocrine cell, uterine cervical, and pancreatic cancers. Lumican expression also correlates with the growth and metastasis of various malignancies. For example, lumican expression is lower in the dermis of malignant melanoma cases than in early-stage melanomas. However, the expression patterns and roles of lumican in nonmelanoma skin cancer have not been elucidated. In this study, we used immunohistochemistry and in situ hybridization to examine the expression patterns of lumican in normal skin, Bowen disease, and actinic keratosis. In normal skin, lumican was expressed in the collagen fibers in the dermis, acrosyringium, follicular epithelium, and sebocytes but not in epidermal keratinocytes. In Bowen disease, lumican was expressed in 34 (91.8%) of 37 patients. Notably, all cases of actinic keratosis were negative for lumican. These findings suggest that lumican plays an important role in the pathogenesis of Bowen disease and actinic keratosis and might be useful as an adjunct to the diagnosis for subtypes of 2 diseases: bowenoid actinic keratosis and Bowen disease in sun-exposed areas.

Interstitial type granuloma annulare associated with Sjögren's syndrome.

We describe a case of granuloma annulare (GA) associated with Sjögren’s syndrome (SS) in a 69‐year‐old woman. She complained of erythematous plaques on the left forearm and neck in addition to dry eyes and mouth. The laboratory and clinical findings also fulfilled the criteria for diagnosis of SS. Histopathological examination revealed the features of interstitial type GA. It is not rare that granulomatous diseases are associated with autoimmune diseases. This case indicated that granulomatous diseases and SS are closely related and that GA should be recognized as a cutaneous manifestation associated with autoimmune diseases, including SS.

Brunsting-Perry type localized bullous pemphigoid, possibly induced by furosemide administration and sun exposure

A 56-year-old male visited our hospital complaining of irregular-shaped atrophic erythematous plaques with blood crust, erosion, pigmentation, and depigmentation, localized on his forehead, bilateral cheeks, and ear lobes, for over one year. He has been receiving peritoneal dialysis and furosemide administration due to chronic renal failure for four years. Direct immunofluorescence examination exhibited linear depositions of IgG and C3 in the basement membrane zone. Antibodies against the recombinant NC16a-domain of BP180 were negative by enzyme-linked immunosorbent assays (ELISA), though BP230 ELISA was positive. Immunoblotting using extracts of normal human epidermis demonstrated that the patients serum reacted with BP180 and BP230. IgG class autoantibodies to recombinant proteins of the C-terminal domain of BP180 were also detected by immunoblotting. This case was diagnosed as localized bullous pemphigoid (LBP). Oral administration of prednisolone 10 mg daily was started and furosemide administration was ceased. The eruptions disappeared thereafter with superficial scars. This is the second reported case of Brunsting-Perry type LBP associated with IgG class autoantibodies to the C-terminal domain of BP180. Furthermore, photosensitivity caused by furosemide administration may contribute to the induction and exacerbation of the lesions.

Histopathological diagnosis of epithelial crateriform tumors: Keratoacanthoma and other epithelial crateriform tumors.

Keratoacanthoma (KA) is a unique and distinct clinicopathological entity, although there is often confusion regarding its differentiation from other types of crateriform tumors. In this study, the clinicopathological features of 380 epidermal crateriform tumors with a central keratin plug were re‐examined and the tumors were histologically classified into seven types: (i) crateriform verruca; (ii) crateriform seborrheic keratosis; (iii) KA; (iv) KA with a conventional squamous cell carcinoma (SCC) component (KA‐like SCC and KA with malignant transformation); (v) crateriform Bowens disease; (vi) crateriform SCC arising from solar keratosis; and (vii) crater form of infundibular SCC. Our study proved that incidence of SCC developing in KA lesions was 17.4%. The incidence rate differed depending on a patients ages: 8.3% in patients less than 70 years of age and 24.3% in those aged 70 years and older. Nearly all of the malignant crateriform neoplasms (94.7%) occurred on sun‐exposed areas. Lesions on the face included 138 KA (59.5%), 65 malignant crateriform neoplasms (28%) and 29 benign crateriform neoplasms (12.5%). We conclude that KA is not a variant of SCC, but a benign and frequently regressing proliferative lesion or borderline neoplasm, although there is the potential for SCC to arise within KA. Because the incidence of SCC developed in KA lesions and the incidence of other malignant crateriform neoplasms are higher in patients aged 70 years and older, KA‐like lesions on sun‐exposed areas over 70 should be assessed carefully in consideration of the potential risk of malignancy.

Case of anti-laminin gamma-1 pemphigoid with antibody against C-terminal domain of BP180 in a patient with psoriasis vulgaris

against each component of BMZ (Fig. 1d). IgA and laminin-332 were detected on the dermal and epidermal sides of the blister, respectively (Fig. 1e). Type 4 (Fig. 1f) and type 7 collagen (Fig. 1g) were detected above the IgA deposit and on the dermal side of the blister. IgA deposits were observed above the elastic fibers (Fig. 1h). We diagnosed this case as DH, and DDS (75 mg/day) was started. The skin lesions improved and DDS was decreased to 25 mg/day with a favorable course. Immunomapping findings of DH have been described in two previous reports. Our study clearly showed that the level of cleavage was between type 7 collagen and laminin-332 in this case, similar to in epidermolysis bullosa acquisita and different from bullous pemphigoid, as demonstrated in our previous study. The vesicles of DH are recognized to develop in the lamina lucida based on the previous studies. Klein et al. studied seven DH patients and laminin was found on the floor of vesicles in five patients, while on the roof of vesicles in two patients. Smith et al. studied six biopsies, and laminin was found on the floor of the vesicle in three biopsies, while both on the floor and on the roof in one biopsy, and no staining in two biopsies. They speculated that the poor staining was attributed to destruction of laminin by the blistering process. These results suggest that the staining with anti-laminin antibody provides several different patterns in different patients, and that it may be difficult to conclude the cleavage site only from one patient. Laminin-332 on the floor of the bulla in our case might have been destructed, so that only laminin332 on the roof was detected, as suggested by Smith et al. However, we could also speculate that the difference in the staining pattern may be due to the difference in antibodies used, or to the difference in ethnic groups as suggested in the literature. Further immunomapping studies will be necessary to verify our speculation.

CD117 (KIT) is a useful immunohistochemical marker for differentiating porocarcinoma from squamous cell carcinoma

Distinguishing porocarcinoma from squamous cell carcinoma (SCC) is clinically significant but can pose a diagnostic dilemma. The present study sought to confirm the diagnostic utility of CD117 immunohistochemistry in distinguishing porocarcinoma from SCC and to examine histologic, carcinoembryonic antigen (CEA) immunohistochemical and CA19‐9 immunohistochemical differences between these tumors.