Yasutaka Tokuda

Chronic obesity lymphoedematous mucinosis: three cases of pretibial mucinosis in obese patients with pitting oedema

Pretibial mucin deposition on the shins is known as pretibial myxoedema. We report three patients with pretibial mucinosis without thyroid disease. The patients were characterized clinically by morbid obesity and bilateral lower extremity pitting oedema with gradual and painless onset, and that did not involve the feet and ankles. Vesicles, semitranslucent papules or a woody plaque were found on the shins. Histologically, patients showed characteristic features of epidermal atrophy with effacement of the rete ridge pattern, separation of collagen bundles associated with oedema with stellate to linear fibroblasts, upward‐running increased capillary and small vessels with haemosiderin deposition, and mucin deposition at the superficial papillary dermis and around the vessels. We propose that the present cases of ‘chronic obesity lymphoedematous mucinosis’ belong to the clinical entity of pretibial mucinosis.

Distribution patterns and frequency of proliferating cells in cutaneous keratinocytic neoplasms: Immunohistochemical study with a monoclonal antibody (TOB7) used against proliferating cell nuclear antigen

BACKGROUND Almost all markers for proliferating cells need freshly frozen tissues for evaluation; therefore retrospective study is impossible. OBJECTIVE In the present study, a murine monoclonal antibody (TOB7) against the proliferating cell nuclear antigen (PCNA) was used for the analysis of cell kinetics of cutaneous keratinocytic neoplasms. The antibody is applicable to formalin-fixed, paraffin-embedded tissues. METHODS The frequency of PCNA-positive cells and their distribution patterns were immunohistochemically investigated in various cutaneous keratinocytic neoplasms. RESULTS Squamous cell carcinoma and Bowens disease showed significantly increased numbers of PCNA-positive cells when compared with other keratinocytic neoplasms. A characteristic marginal or random distribution pattern of PCNA-positive cells was observed in the lesions of each disease category. CONCLUSION Important information on the growth dynamics of keratinocytic neoplasms was obtained in this retrospective immunohistochemical study.

Growth dynamics of acquired melanocytic nevi: Higher reactivity of proliferating cell nuclear antigen in junctional and compound nevi than intradermal nevi

BACKGROUND The histogenesis of acquired melanocytic nevi is still a matter of debate. OBJECTIVE To provide data on the histogenesis, we investigated the lesional area of acquired melanocytic nevi and the proliferative activity of the nevus cells. METHODS Proliferative activity was examined with a monoclonal antibody against proliferating cell nuclear antigen (PCNA). The lesional area of the nevus was estimated in histologic sections. RESULTS Intradermal nevus was the largest of the acquired melanocytic nevi but had few PCNA-positive nevus cells. In contrast, junctional nevi were smallest and showed the highest PCNA positivity. Statistical analysis showed a significant inverse correlation between the largest lesional area and PCNA positivity. CONCLUSION The findings of the present study are in accordance with an epidermal melanocytic origin of acquired melanocytic nevi.

A case of an inflammatory variant of epidermolysis bullosa acquisita: Chronic bullous dermatosis associated with nonscarring mucosal blisters and circulating IgG anti-type-VII-collagen antibody

A 42-year-old man showed prominent blistering lesions of the mouth and esophagus in addition to a few bullous lesions of the skin. Direct immunofluorescence microscopy revealed distinct linear deposition of IgG and C3 at the epidermal basement membrane zone where slight deposition of IgA and IgM was also observed. In direct immunoelectron-microscopic examination, antibody was detected in the sublamina densa of the basement membrane zone. Immunoblot analysis with dermal extracts demonstrated that the patient’s serum contained circulating IgG antibodies against the 290-kD protein, which comigrated with type VII collagen. The lesions healed without any scars. The results of these studies corresponded to the laboratory findings in epidermolysis bullosa acquisita (EBA), although the clinical features were distinct from classic EBA.

New immunodeficient (nude-scid, beige-scid) mice as excellent recipients of human skin grafts containing intraepidermal neoplasms.

Engraftment of normal or lesional human skin onto nude or SCID (severe combined immunodeficiency) mice has been used as an in vivo experimental model. However, this model has some limitations, such as shrinkage and loss of the grafted skin over time. To improve the experimental model, we have produced two new SCID-lineage mouse strains, BALB/cA-nude-scid (nu/nu, scid/scid) and BALB/cA-beige-scid (bg/bg, scid/scid) mice, by the method of cross intercross. Intraepidermal neoplastic lesions such as Bowen’s disease were grafted onto the back of the mice of these strains. The rate of reduction in the size of the grafts was lower on nude-scid and beige-scid mice than on SCID mice. Rates of survival of neoplastic cells in the grafts were higher in nude-scid mice than in SCID and beige-scid mice (SCID mice 38%, nude-scid mice 55%, beige-scid mice 38%). Neoplastic cells of Bowen’s disease grafted onto a beige-scid mouse proliferated and invaded the dermis during 233 days of observation, confirming the progression to invasive squamous cell carcinoma from carcinoma in situ. The present study revealed that nude-scid and beige-scide mice newly produced by us provide a very useful in vivo experimental model for the investigation of carcinogenesis and tumor progression in human skin.

EFFECTIVE DETECTION OF PLANTAR MALIGNANT MELANOMA

Background: As the sole of the foot is the most prevalent site of malignant melanoma in non‐Caucasians, early detection of the neoplasm at this anatomical site is very important. In our previous study, we proposed a clinical guideline that acquired melanocytic lesions on the sole larger than 7 mm in maximum diameter should be examined histologically.

A case of primary Epstein-Barr virus-associated cutaneous diffuse large B-cell lymphoma unassociated with iatrogenic or endogenous immune dysregulation.

Cutaneous Epstein‐Barr virus (EBV)‐associated B‐cell lymphoma (EBVBL) in non‐immunocompromised patients is very rare. Here, we report a case of cutaneous EBVBL in a 72‐year‐old Japanese woman without any signs of immunosuppression. She showed repeated high fever and skin eruptions on the face, limbs and palms. Histological diagnosis was diffuse large B‐cell lymphoma. EBV infection was detected by in situ hybridization and Southern blotting. Immunostaining for viral proteins showed the patient to be positive for latent membrane protein 1 (LMP‐1) and negative for Epstein‐Barr virus nuclear antigen‐1 (EBNA‐2), indicating that a type II latency EBV infection pattern.

Acral pseudolymphomatous angiokeratoma of children: a case report with immunohistochemical study of antipodoplanin antigen.

Acral pseudolymphomatous angiokeratoma of children (APACHE) is characterized by multiple angiomatous papules on the hands and feet in children. Here, we report a case of APACHE in a female patient followed up from 13 to 19 years of age with a dark red lesion on the center of the dorsum of the right thigh. Histologically, vacuolar alteration and exocytosis of lymphocytes, and specific dense cellular infiltration beneath the epidermis to the reticular dermis were found. On immunolabeling study, the lesion vessels were found to be positive for both the lymphatic endothelium-specific marker podoplanin and blood vessel-specific marker CD34. These findings suggested that APACHE is a type of vascular malformation.

Engraftment of precursor lesions of human cutaneous neoplasms onto C.B-17 SCID mice: a useful in vivo experimental model of carcinogenesis in human skin.

Using a full-thickness skin grafting technique, lesional skin from various human neoplastic and preneoplastic skin diseases was transplanted onto SCID (severe combined immunodeficiency) mice. Of 27 grafted lesions, 21 were successfully accepted by the mice and maintained in good condition. All these accepted grafts were finally excised 10–101 days after transplantation for histological examination. In most grafts, the characteristic histological configurations of each disease were well preserved. Immunohistochemical study using monoclonal antibodies to human blood group antigens ABH revealed that some elements of the grafts such as sweat glands were clearly positive, confirming that the tissue was from human skin. Neoplastic (atypical) cells were detected in 9 of 17 accepted grafts containing neoplastic cells from the beginning. The detection rates for neoplastic cells were very high (90%) in grafts from precursor lesions of squamous cell carcinomas such as Bowens disease (5/5 specimens) and thermal keratosis (2/3). In contrast, no definite neoplastic cells were found in two grafts from extramammary Pagets disease and five grafts from the radial growth component of malignant melanoma. In most of the grafts from latter two diseases, characteristic histological configurations such as elongation of the rete ridges were maintained, suggesting that the neoplastic cells were selectively eliminated from the grafts. Split-thickness grafts of normal human skin were accepted and remained in a good condition for as long as 6 months. Engraftment of human lesional and non-lesional skin onto SCID mice therefore may well provide a useful in vivo experimental model of human skin diseases.

Histogenesis of congenital and acquired melanocytic nevi based on histological study of lesion size and thickness

The histogenesis of melanocytic nevi is poorly understood. It is important to determine the differences and similarities in histogenesis between congenital and acquired nevi. To clarify the histogenic differences between acquired melanocytic nevi (AMN) and congenital melanocytic nevi (CMN), diameter and depth of nevus cells (tumor thickness) were examined in histological specimens from 80 cases of CMN and 71 cases of AMN, and these nevi were classified according to Mark’s pathological CMN criteria. In all cases, giant CMN nevus cells were found in the lower marginal portion of excised specimens. The mean diameter and lesional thickness were significantly higher in CMN than in AMN. AMN diameter showed a significant correlation (r = 0.567, P < 0.05) with lesional thickness, while no such relation was observed in CMN. In addition, a significant correlation between lesion diameter and thickness was observed in small (<10 mm) non‐Mark’s type CMN (r = 0.626, P < 0.05). CMN may be classified into three subtypes: (i) caused by increased proliferation of melanoblasts during the course of migration from the neural crest to the epidermis; (ii) proliferation of nevus cells after arrival at the epidermis, and nevus cell distribution affected by adnexa and dermal differentiation; and (iii) arising after completion of skin development before birth.