Kenji Saga

The chilblain-like eruption as a diagnostic clue to the blast crisis of chronic myelocytic leukemia

A 70-year-old Japanese man visited our clinic with the chief complaint of chilblain-like eruptions on the toes of both feet. His toes were bluish, erythematous, and swollen. Neither oral administration of vitamin E for 2 weeks nor wearing insulated socks improved the clinical manifestations. Peripheral blood examination revealed the presence of a large number of monocytic atypical cells and myeloblasts, anemia, and thrombocytopenia. In the bone marrow, monocytic cells were elevated, and myelocytic atypical cells were observed. Chromosomal analysis demonstrated Philadelphia chromosome. We diagnosed him as having a blast crisis of chronic myelocytic leukemia (CML). A biopsy specimen of the skin from the chilblain-like eruption showed infiltration of large, atypical, mononuclear cells; most of them were positive for CD68, and some of them were positive for CD14. Therefore, we concluded that the chilblain-like eruptions on his toes were specific skin lesions of a blast crisis in CML.

In-vitro DNA synthesis of keratinocytes in normal human skin, psoriasis, seborrhoeic keratosis, Bowen's disease and basal cell carcinoma

The DNA‐synthesizing cells in benign and malignant keratotic diseases including psoriasis, seborrhoeic keratosis, Bowens disease and basal cell carcinoma were studied. Cells in S‐phase were labelled after small pieces of the lesions were incubated in tissue culture medium that contained 5‐bromo‐2′‐deoxyuridine (BrdU). The labelling of DNA was analysed using the labelling index and pattern. Although the malignant diseases tended to show a higher DNA labelling index, neither this nor the loss of polarity alone was associated with malignancy. However, a higher DNA labelling index together with a loss of polarity was characteristic for malignancy.

Idiopathic acquired generalized anhidrosis due to occlusion of proximal coiled ducts

Idiopathic acquired generalized anhidrosis is a very rare disease of unknown pathogenesis. We report a 25‐year‐old man with acquired generalized anhidrosis due to occlusion of the coiled ducts. He did not have sweat secretion over the entire surface of the body, including the palms and soles. Sweat‐inducing stimuli provoked tingling pain on the skin. Pilocarpine iontophoresis on the forearm did not induce sweat secretion. Neurological examination did not reveal any abnormality in the central or peripheral nervous system. Skin biopsy showed that the coiled ducts were occluded by an amorphous eosinophilic substance. This amorphous eosinophilic substance was positive with periodic acid–Schiff (PAS) staining and was resistant to digestion by diastase. Electron microscopy demonstrated that the coiled ducts were completely occluded by an amorphous substance. The substance occluding the coiled ducts contained fibrous structures. These findings suggested that the acquired generalized anhidrosis in this patient was caused by occlusion of the coiled ducts by a PAS‐positive substance probably derived from dark cell granules.

Acquired multiple pilosebaceous cysts on the face having the histopathological features of steatocystoma multiplex and eruptive vellus hair cysts

A 59-year-old Japanese woman had a persistent skin eruption located on the face for 5 years’ duration. These asymptomatic yellowish papules had gradually increased in number. She had approximately 30 lesions, 1–3 mm in diameter, with a smooth surface (Fig. 1). No other area of the body had a similar eruption. There was no other relevant family history of similar lesions. No tendency to remission was observed. Histopathology of the lesion excised from her right cheek showed a cyst in the mid-dermis that was lined by 3–4 cell layers of undulating squamous epithelium (Fig. 2). Crenulated, homogenous and eosinophilic cuticle lined the keratinous cyst. An overlying epidermis was normal. The cyst was filled with amorphous, laminated keratinous material and numerous vellus hair shafts (Fig. 3). A sebaceous gland was attached to the deepest part of the cyst wall (Fig. 2). A telogen hair follicle was not connected to the cyst wall. The cyst was diagnosed as a facial papular variant of steatocystoma multiplex (SM) with overlapping features of eruptive vellus hair cysts (EVHCs).

Postmenopausal frontal fibrosing alopecia in a Japanese woman with Sjögren's syndrome

Postmenopausal frontal fibrosing alopecia (PFFA) is a rare alopecia that develops in the frontoparietal scalp of postmenopausal women. Etiology of PFFA is unknown. Most of cases of PFFA have been reported in European and North American countries. Herein, we report a Japanese case of PFFA associated with Sjögrens syndrome. A 66‐year‐old woman had had slowly progressive, band‐like, scarring alopecia on her frontoparietal scalp. Hair follicles on the margin showed follicular keratosis. Histologically, fibrosis and lymphocytic infiltration were mild. This case suggests that PFFA may show mild inflammatory reaction and mild fibrosis in Japanese women. The association with immunological disorders including Sjögrens syndrome should be studied further.

Small cell variant of CD30+ primary cutaneous T-cell lymphoma with epidermotropism that completely regressed after incisional skin biopsy

rates of 25%, 45%, 83% and 100%, respectively. The probability of provocation was modelled using binary logistic regression in an equation with PLESI, current age, years since onset of PLE, buttock MED, gender, skin type and positive family history as predictor variables. All these variables, except the PLESI score, were not significant and were sequentially removed from the model. The resultant equation had the PLESI score as a single predictor variable (P 1⁄4 0Æ01) and was: P 1⁄4 exp ()2Æ93 + 0Æ062 · PLESI)/ [1 + exp ()2Æ93 + 0Æ062 · PLESI)]. This equation describes a sigmoid curve (see Fig. 1). In the model, the probability of successful provocation with PLESI scores of 25, 50 and 75 was 20%, 54% and 84%, respectively. The mean PLESI score of those not provoked and those provoked by three, two and one exposures was 46Æ5 (n 1⁄4 14), 51Æ3 (n 1⁄4 8), 69Æ3 (n 1⁄4 11) and 59Æ4 (n 1⁄4 3), respectively; this upward trend was significant (rs 1⁄4 0Æ42, P 1⁄4 0Æ01), despite the low last value. The use of SSR may not be the optimal method for provocation; for example, a source emitting wavelengths almost entirely in the UVA range might provoke a greater proportion of patients. Although further studies to assess the relationship between PLESI score and outcome of provocation are desirable, we have shown that the PLESI is associated with the likelihood of experimental provocation of the rash. This suggests that investigators wishing to provoke the eruption experimentally will benefit by selecting patients with high PLESI scores, and provides further validation of the PLESI. To interpret the results of PLE research fully, the severity of the disease in participating subjects needs to be known. Therefore, studies of the provocation, prevalence, pathogenesis and treatment of PLE would benefit by using the PLESI to consider disease severity in participating patients. Acknowledgments

Application of cryofixation and cryoultramicrotomy for biological electron microscopy.

Conventional chemical fixation and embedding of specimens in resins are accompanied by many artifacts, including postmortem structural alterations. Antigenicity of constituents of specimens can be deteriorated and soluble elements relocated in the process of chemical fixation and resin-embedding. Cryofixation and cryoultramicrotomy will overcome many of these drawbacks of chemical fixation and resin embedding. The theoretical background, equipment, methods, and applications of cryofixation and cryoultramicrotomy for biological specimens are reviewed.

Immunohistochemical Localization of Activated EGF Receptor in Human Eccrine and Apocrine Sweat Glands

Epidermal growth factor (EGF) is secreted into sweat from secretory cells of human sweat glands. The function of EGF in sweat is poorly understood. The biological function of EGF is exerted by the binding of EGF to the receptor (EGFR) and its activation. Therefore, we immunohistochemically localized the activated form of EGFR in human eccrine and apocrine sweat glands to assess the functional importance of the EGF–EGFR system in human sweat glands. Frozen sections of human skin were stained with a monoclonal antibody (MAb) specific for tyrosine-phosphorylated (activated) EGFR and with an MAb that stains both activated and non-activated EGFR. In the secretory portion of eccrine sweat glands, nuclei of the secretory cells were stained with the anti-activated EGFR MAb. In coiled and straight portions of eccrine sweat ducts, nuclei of luminal and peripheral cells were stained with the antibody specific for activated EGFR. Luminal cell membranes and luminal cytoplasm of inner ductal cells possessed non-activated EGFR. In the secretory portion of apocrine sweat glands, activated EGFRs were present in cytoplasm and nuclei of secretory cells. These data suggest that EGF, already known to be present in the cytoplasm of secretory cells in eccrine and apocrine sweat glands, activates EGFR in the nuclei of secretory cells themselves in an intracrine manner. Because ductal cells do not express EGF, EGF in the sweat secreted from the secretory cells should activate EGFR in the ductal cells in a paracrine manner. (J Histochem Cytochem 49:597–601, 2001)

Nodular scleritis and panuveitis with erythema elevatum diutinum

PURPOSE To report a case of nodular scleritis and panuveitis associated with erythema elevatum diutinum, a rare immunocomplex-mediated skin disease. DESIGN Observational case report. METHODS A 22-year-old woman who was diagnosed with erythema elevatum diutinum developed nodular scleritis and panuveitis of the right eye. She had experienced peripheral ulcerative keratitis with corneal perforation. RESULTS All other known causes of nodular scleritis and panuveitis were investigated and ruled out. CONCLUSIONS Erythema elevatum diutinum should be considered as an underlying systemic disease associated with nodular scleritis and panuveitis as well as peripheral keratitis.

Localization of anionic sites in normal and psoriatic epidermis : the effect of enzyme digestion on these anionic sites

Cell surface anionic charge is known to be related to various cellular functions. Therefore, we ultrastructurally localized anionic sites in normal and psoriatic human epidermis, using poly‐l‐lysine‐gold complex (cationic gold), to assess their possible participation in the differentiation of keratinocytes and the pathogenesis of psoriasis. In normal and psoriatic epidermis, the cell membrane of keratinocytes showed positive staining at pH 2.0. At pH 7.4 the cytoplasm and nucleus were diffusely stained, in addition to the cell membrane. In normal epidermis, the intensity of labelling on the cell membrane at pH 2.0 was strong in the basal layer and lower stratum spinosum, and decreased in parallel with differentiation of keratinocytes. In psoriatic epidermis, the intensity of labelling on the cell membrane at pH 2.0 was stronger than in normal epidermis. In normal epidermis, heparitinase digested 63% and chondroitinase ABC digested 80% of cationic labelling. This suggests that heparan sulphate and chondroitin sulphate (and/or dermatan sulphate) constitute anionic sites in normal epidermis. In psoriatic epidermis, chondroitinase ABC‐sensitive anionic sites were greatly increased, whereas heparitinase‐sensitive anionic sites were the same, when compared with normal epidermis. This suggests that chondroitin sulphate and/or dermatan sulphate constitute anionic sites which are increased in psoriatic epidermis.