Toshiyuki Aki

OSTEOSARCOMA Ultrastructural and Immunohistochemical Studies on Alkaline Phosphatase‐positive Tumor Cells Constituting a Variety of Histologic Types

The osteosarcomas were subclassified into osteoblastic, fibroblastic, chondroblastic and telangiectatic types and examined by electron microscopy. Their immunohistochemical reactions were also studied. In an overall survey of the above types, fibroblast‐like cells revealed poorly developed cytoplasmic organelles with rather short, branching rough endoplasmic reticulum, mixed with osteoblast‐like cells that were hardly distinguishable from the former. They appeared to be an early stage of an osteoblastic cell lineage from the distribution and development of their cell organelles and highly positive vimentin activity. The tumor cells in malignant cartilage varied in appearance from chondroblast‐like to osteoblast‐like cells. All types of tumor cells expressed alkaline phosphatase activity to a significant degree. Immunohistochemical staining showed a mixture of procollagen type I‐positive cells among the cells positive for both procollagen type II and S‐100 protein in the malignant cartilage. Irrespective of any ultrastructural differences between these various tumor cell types, they all revealed a significant degree of ALPase activity unlike other types of bone tumors, suggesting that the tumor cells which constitute the various types of osteosarcoma are derived from a common precursor cell.

Extramammary Paget’s Disease in Siblings

This report describes extramammary Paget’s disease (EMPD) developed in siblings, both of whom had an internal malignancy. Case 1, an 83-year-old Japanese woman, was first seen in our department on May 11, 1987, with an itchy lesion in the vulvar region. She had noticed itchy erythema in the vulvar region 10 months before and a nodule had developed on the erythematous lesion 2 months later. History revealed that she had undergone breast cancer surgery at the age of 51. Physical examination revealed an undefined erythematous lesion from the mons pubis to the bilateral large and small pudendal lips and a nodule measuring 3 ! 3 ! 2 cm on the upper portion of the right large pudendal lip. A biopsy specimen from the nodule showed that the normal dermal components were replaced by Paget’s cells extending into the subcutaneous fatty tissues. Thus, the lesion was interpreted as invasive EMPD. Case 2, an 83-year-old Japanese man, was first seen in our department on September 1, 1998, with itchy erythema on the scrotum. He had noticed itchy erythema on the scrotum 1 year before and a tumor had occurred on the erythematous lesion 10 months later. His older sister (case 1) had invasive EMPD. Physical examination revealed an erythematous lesion with erosion on the left scrotum to the basal portion of the penis. An elastic tumor measuring 1.5 ! 1.5 cm on the central portion of the lesion was palpated: A biopsy specimen from the tumoral lesion revealed that Paget’s cells invaded the entire dermis, indicating invasive EMPD. By further careful examination, a gastric cancer was detected and was radically resected by distal partial gastrectomy. The resected gastric cancer was histologically diagnosed as well-differentiated adenocarcinoma. In 1973, Kuehn et al. [1] reported a father and his son affected with EMPD, and they indicated that one might hypothesize a linkage between genetic abnormality and predisposition to cancer. Since then, there have been 6 reports [2–6] including our case for occurrence of siblings with EMPD. However, there is no report of a father or a mother with EMPD who has a child with EMPD apart from the initial report by Kuehn et al. [1]. Thus, even if there is some indication that EMPD may occur in families, firm evidence for a genetic predisposition is lacking. Our case 1 had breast cancer approximately 32 years before the occurrence of EMPD; likewise our case 2 had simultaneously gastric cancer. Since Helwig’s and Graham’s indication [7], EMPD has been considered as a cancer-prone disease. Chanda [8] suggested a strong correlation between the anatomic site of EMPD and concurrent internal malignancy. Although this correlation suggests the possibility that similarly derived embryologic tissue may be susceptible to similar carcinogenic stimuli and may undergo malignant degeneration simultaneously [8], the anatomic site of EMPD and the associated internal cancer in our cases cannot be included in the category. Recently, Takata et al. [9] indicated that invasive EMPD tumors frequently showed erbB-2 protein overexpression. Similarly, breast, ovarian and gastric cancers showed erbB-2 gene amplification and/or erbB-2 protein overexpression. All these cancers including invasive EMPD belong to adenocarcinoma, and therefore erbB-2 gene amplification and/or erbB-2 protein overexpression may play an important role in the tumorigenesis of adenocarcinoma, particularly invasive growth of EMPD.

“Thermie” and friction therapy performed using a special instrument

“Thermie” therapy is one of the folk remedies in Japan and is mainly done by rubbing the skin with special instruments. The therapy is believed to relieve several symptoms which include pain, common cold and ileus. We report here the first two cases of thermie dermatosis in the English published work. The first patient had suffered from poikiloderma‐like eruptions for 30 years after the initiation of a thermie therapy. The eruptions were on both the upper back and the abdomen. The second patient presented with a hyperpigmented plaque on the right femoral region, and excoriated papules and a hyperpigmented plaque on the left lower leg. The patient had received thermie therapy for 3 years. The histopathology of the first case revealed features of cutaneous amyloidosis, and, of the second case, superficial dermatitis and hypermelanosis in the epidermal basal layer. A common cause of both cases was regarded as the thermie therapy. This report suggests the importance of getting a thorough history including folk remedies in patients presenting such pigmented lesions.

Peripheral T-cell Lymphomas Immunologic and Enzyme Histochemical Analysis of 15 Cases

Ffteen cases of peripheral T cell lymphoma were studied to evaluate the respective properties of various histologic types using enzyme histochemical and ultrastructural examinations in addition to immunological methods. Eleven cases in an ATLA negative group manifested various histologic patterns such as IBL like, pleomorphic and Lennerts lymphomas in comparison with the relatively monomorphic proliferation of neoplastic lymphoid cells in the 4 ATLA positive cases. The presence of neoplastic clear cells is characteristic of peripheral T‐cell malignancies, and is likely to be found in CD4 lymphomas. There is an occasional reaction of epithelioid histiocytes and plasma cells with eosinophils, the former being designated Lennerts lymphoma and the latter IBL like T‐cell lymphoma. Immunological examination revealed four immunophenotypic patterns: (1) CD2+3+4+8+, (2) CD2+ 3−4+8−, (3) CD2+3+4−8+, and (4) CD2+3+4+8+, but did not provide information concerning the intimate relationship between histologic types and immuno phenotyes. β‐Glucuronidase reactivity, however, contributed to the distinction between helper and suppressor T cell malignancies, suggesting its usefulness for distinguishing these two cell types and their malignant counterparts.

A case of zinc deficiency histologically showing spongiform pustules of Kogoj.

An 89-year-old Japanese woman was referred to us for evaluation of multiple scaly erythematous plaques with erosions that had developed over her entire body. She had received enteral feeding because of eating disorders for 9 months. Although she had been treated with topical steroid ointment and oral administration of prednisolone and terbinafine before admission to our department, there was no response. Due to concurrent severe diarrhoea, she was also treated with intravenous antibiotics (imipenem), but the treatment was not effective. Physical examination revealed multiple erythematous plaques with oedema, irregular in shape, on her face, especially around the eyelids, vulva, trunk and extremities (Fig. 1). The centre of each erythema was erosive, and some pustules were observed on the surface. Laboratory examinations demonstrated the following values: white blood cell count 13.2 × 109/l; C-reactive protein 6.9 mg/dl; serum zinc level 5.2 μmol/l (normal range 9.2–20 μmol/l). No fungus was found on the erythema. A biopsy specimen taken from the erythema with pustules showed hyperkeratosis, parakeratosis, acanthosis and subcorneal spongiform pustules of Kogoj (Fig. 2). Based on these findings, a diagnosis of zinc deficiency was made. Supplementation of zinc by oral administration of zinc sulphate for 2 weeks improved the skin lesions.

Case of self-inflicted skin ulceration

Dear Editor, Self-inflicted skin diseases such as neurotic excoriation, dermatitis artefacta and delusion of parasitosis often present unusual manifestations. It has been reported that those are associated with personality disorders, psychoses, Munchausen’s syndrome and malingering, and it is sometimes difficult to make a correct diagnosis and treat. The commonest of factitious dermatoses is neurotic excoriation. Although neurotic excoriation is caused by the patients themselves as a result of repetitive infliction, it differs from other self-inflicted skin diseases in that the patients usually admit to their production of the lesions because of underlying their personality, obsessive–compulsive disorder and depressive disorder. However, as far as we know, a case of severe undermining ulcer caused by neurotic excoriation has not been reported in Japan, so far. We describe here a case of recurrent intractable ulcer on the scalp of a 46-year-old Japanese man – who had been suffering from sleep apnea syndrome – due to neurotic excoriation. A 46-year-old Japanese man was referred to our hospital with a 1-year history of an ulcer on the scalp. Initially, he had been aware of an asymptomatic nodule on the occipital region, and repeatedly scratched it because of itch, causing an ulcer. He also complained of vague anxiety. The patient admitted that the ulcer was produced by self-infliction. His medical history was obesity (height, 172 cm; weight, 106 kg) and sleep apnea syndrome. On physical examination, a 11.5 cm × 8 cm ulcer was observed on the right temporal region (not shown). A biopsy specimen from the ulcer showed fibrosis and granulation tissue (not shown). There was no evidence of infection, vasculitis, malignancy or contact allergy to any ointments. The lesion was diagnosed as self-inflicted dermatosis, so-called neurotic excoriation. However, the patient stopped coming to our clinic after the diagnosis. After 10 months, he returned to us again because of severe pain due to the ulcer (Fig. 1). We consulted a psychiatrist at our institution about his condition. A psychiatrist evaluated that his complaint of anxiety was not pathological but based on his character. It was difficult to administer antidepressant drugs to him because of his sleep apnea syndrome. Dietetic treatment had no effect on his obesity. Hypnosis was not tried. He was hospitalized for 2 months and the ulcer was reduced in size and depth temporarily after the topical application of antibiotics and alprostadil alfadex ointment. He was discharged from our hospital. A 15 cm × 5 cm ulcer reappeared on his occipital region and he was referred to us 2 years later. After a course of antibiotics treatment, shower disposal and a carboxymethyl cellulose dressing, the ulcer was reduced in size and depth. He was discharged 3 months later and received the topical treatment continuously at the local hospital. However, he was referred to us again 16 months later. On examination, a 6 cm × 5 cm ulcer was present

Examination on sunlight hyperkeratosis and tissue-type of SCC from the same disease.

Although solar keratosis (SK) is commonly classified histologically into five types i.e., hypertrophic, atrophic, acantholytic, bowenoid and pigmented types, we added another type, spongiotic clefting type, which has spongiotic suprabasal cleft. Squamous cell carcinoma (SCC) derived from SK has been reported to have such histologic types as de novo, acantholytic and bowenoid SCCKs and small celled carcinoma. Of 109 cases of SK studied, hypertrophic type was 56.9%, atrophic type 5.5%, acantholytic type 4.6%, bowenoid type 17.4% and spongiotic clefting type 15.6%, respectively. Of 17 cases of SCC from SK, de novo type was 23.5%, acantholytic type 47.0%, bowenoid type 5.9%, and small celled carcinoma 23.5%, respectively. Acantholytic type of SCC having the highest rate of occurrence, possibly, derives from acantholytic type of SK. Thus, it is supposed that tumor cells of acantholytic type of SK have higher tumor invading rate. Using PCNA and AgNORs as index of cell proliferating rate, we examined all types of SK. However we could not have any significant difference among them.