Malignant neuroepithelioma (peripheral neuroblastoma). A clinicopathologic study of 15 cases.

A clinicopathologic study of 15 cases of malignant neuroepithelioma (peripheral neuroblastoma) of soft tissues is reported. The patients were chiefly young Japanese adults with a median age of 21 years. The tumors arose mainly in the soft tissues of the lower extremity (seven cases) and the trunk (four cases). Microscopically, there were sheets of closely packed, small round or oval cells, and Homer Wright-type rosettes were seen in all cases, one of which also had Flexner-type rosettes. Immunohistochemical cytoplasmic localization of neuron-specific enolase (NSE) was demonstrated in six of the eight cases, using the peroxidase-antiperoxidase (PAP) method. In no case, however, was there any staining reaction for S-100 protein. Of the 14 patients for whom follow-up information could be obtained, nine died within a period of 2 years and two were alive and well for over 5 years after the initial treatment. Differential diagnosis from other soft-tissue round-cell sarcomas, such as embryonal or alveolar rhabdomyosarcoma, extraskeletal Ewing's sarcoma, and others, are briefly discussed, on a clinicopathologic basis.

The proliferative properties of tumor cells differentially correlate with the host immune responses in anogenital Bowen's disease.

Bowen's disease is a squamous cell carcinoma in situ that rarely invades into the underlying dermis. In order to evaluate the relationship between the cytological properties of the tumor cells and the host immune response, we have examined the expression of p53 and proliferating cell nuclear antigen (PCNA), and the number of mitotic cells, clumping cells, koilocytes, Langerhans cells (LCs) and dermal lymphoid cell infiltration in 18 cases of anogenital Bowen's disease. When compared with normal anogenital skins (n = 10), a statistically significant number of p53-positive cells, PCNA-positive cells, mitotic cells, clumping cells, koilocytes and dermal lymphoid cells was observed in the cases of Bowen's disease. Importantly, there existed a very strong correlation between the number of PCNA-positive tumor cells and the number of infiltrated dermal lymphoid cells. Moreover, the number of mitotic cells significantly correlated with the number of intratumoral LCs. The in situ hybridization technique for human papilloma virus (HPV) demonstrated that the HPV-infected Bowen's disease showed a similar histological and immunohistological pattern as the HPV-non-infected counterparts, except for increased koilocyte formation and decreased p53 positivity. The present data suggest that the proliferative activity of Bowen's disease significantly correlates with the host immune reaction, and that the host immune system may differentially recognize the different cytological properties of tumor cells in the Bowen's disease.

Frequency of dysplastic nevi among nevomelanocytic lesions submitted for histopathologic examination. Time trends over a 37-year period.

All cutaneous nevomelanocytic specimens accessioned for histopathologic examination at Massachusetts General Hospital, Boston, in 1950, 1960, 1970, and 1987 were reviewed. The specimens were categorized as malignant melanoma, acquired or congenital benign nevi, blue nevi, spindle and epithelioid cell nevi, and dysplastic nevi. Other processes such as lentigines were excluded. There was a threefold increase in percentage of patients having nevomelanocytic lesions removed (1.5% in 1950 to 4.6% in 1987) compared with total surgical cases over the 37-year period. A progressive increase in numbers and percentages of dysplastic nevi (among nevomelanocytic surgical cases) was noted over a 37-year interval--2 cases (1% of nevomelanocytic cases) in 1950, 4 cases (2%) in 1960, 23 cases (5%) in 1970, and 189 cases (12%) in 1987. These findings confirm the existence of dysplastic nevi by histopathologic criteria as early as 1950 and illustrate the frequencies of various nevomelanocytic surgical specimens among all surgical specimens at four points in time over a 37-year period at a major referral center for pigmented lesions.

Multiple piloleiomyomas associated with solitary angioleiomyoma.

A 58 year-old male had reddish scattered papules strictly confined to the right side of his upper back and neck, right shoulder, and right upper arm. Additionally, he also noticed a subcutaneous nodule on his left thigh. Histopathological examinations revealed that the papules on the back, nape of the neck, shoulder, and arm were multiple piloleiomyomas, as shown by the proliferation of bundles of smooth muscles in the dermis. The subcutaneous nodule of the thigh was angioleiomyoma with a well-circumscribed lesion composed of smooth muscles and blood vessels. Ipsilaterality and segmentality of the distribution of the papules of piloleiomyomas and probable family history that his mother had similar papules with a similar distribution suggest the nevoid character of our case. Piloleiomyomas are often reported to be associated with leiomyoma of the uterus or other organs. This is the first reported case of multiple piloleiomyomas with solitary angioleiomyoma in the literature.

Late onset systemic lupus erythematosus with lichen planus-like eruption and cardiac tamponade.

A 71-year-old Japanese woman is reported as a case of late onset systemic lupus erythematosus (SLE) with lichen planus (LP)-like eruption and cardiac tamponade. As an initial symptom, our patient had cutaneous lesions clinically and histologically resembling LP, and then the passage of time allowed for the development of additional criteria (lymphopenia, pericarditis) until the diagnosis of SLE could be made. Our case suggests that LP-like eruptions may be one of the unusual variations of late onset SLE and elderly patients with LP-like eruptions should be carefully followed until a final diagnosis can be clearly made.

Erythema induratum in a patient with active tuberculosis of the axillary lymph node: IFN-gamma release of specific T cells.

A 57-year-old woman with tender nodular lesions on her legs, arms, buttocks and face is reported as a case of erythema induratum (EI) with active tuberculosis of axillary lymph nodes. Both skin nodular lesions and lymph nodes responded positively to antituberculous therapy. The patient's peripheral blood mononuclear cells showed a high proliferation and produced interferon-gamma (IFN-gamma) in response to purified protein derivative (PPD). These findings indicate the possibility that PPD-specific T cells, capable of producing IFN-gamma, are likely to be involved in the formation of EI as a type of delayed-type hypersensitivity response to mycobacterial antigens at the site of skin lesions.

Vitamin D3 analogues improve café au lait spots in patients with von Recklinghausen's disease: experimental and clinical studies.

Topical application of vitamin D3 analogues for 6 months was found to be effective in improving the pigmentation of café au lait spots in patients with von Recklinghausen's disease. Treatment of café au lait spots grafted onto nude mice with a vitamin D3 analogue caused suppression of bromodeoxy- uridine uptake in the cells of the basal layer. Vitamin D3 analogues also decreased melanin pigment in café au lait spots after 4 weeks of treatment. Thus, it is considered that long-term application of vitamin D3 analogues is effective both for improving the pigmentation of café au lait spots and suppressing the development of neurofibromas in patients with von Recklinghausen's disease.

Transcription rate of RNA polymerase under rotary torque.

We investigated the transcription rates of RNA polymerases that were subjected to rotational drag. By combining chemical kinetics with mechanical equations, we derived formulas for the transcription rate in the case where the torque was caused by the hydrodynamic drag to DNA rotation.

Malignant melanoma in situ arising in the nail unit of a child.

A very rare case of malignant melanoma in situ of the nail unit of a child is presented. Clinically, a pigmented streak was present on the finger nail of a 3-year-old girl, and the lesion increased in size and in darkness of the color associated with periungual pigmentation in the following two years. Histopathologically, sections showed proliferation of atypical melanocytes, arranged mostly in single units but some in nests, in and above the basal layer of the epithelium and admixed with long dendrites and a few mitotic figures. Pigmented lesions of nail units of children often show fading or loss of pigmentation clinically; however, a biopsy should be done when they show augmentative changes which clinically suggest malignancy, because subungual malignant melanoma can exist even in children, and proper biopsy can detect it in its early stages.

Malignant melanoma cells in the eccrine apparatus.

A case of malignant melanoma arising on the sole of a 75-year-old Japanese man is presented. Histopathologically, in addition to the intraepidermal and intradermal malignant melanoma cells reaching the upper part of the dermis, cells were also found in the deep part of the ductal epithelium of the eccrine apparatus. Melanoma cells, and melanocytic nevus cells as well, are rarely found within the epithelial structure of sweat glands, yet they are frequently found in that of hair follicles. In order to avoid a residue of melanoma cells in the deep part of the eccrine apparatus, a fairly deep excision should be performed even for this melanoma.

A case of cutaneous infection by Exophiala jeanselmei.

A case of cutaneous infection by Exophiala jeanselmei is reported. The patient was a 45-year-old Japanese female. Her skin eruption consisted of a group of erythematous papules on her left cheek to which corticosteroid had been topically applied for nearly 10 years. Histopathologically, a granuloma formation was noted in the dermis within which were many brown spores. The isolated fungus was identified as Exophiala jeanselmei.

Cutaneous CD30 (Ki-1)-positive anaplastic large cell lymphoma preceded by Hodgkin's disease.

A 38-year-old female was diagnosed as Hodgkin's disease of the axillar lymph nodes, nodular sclerosis type, as evidenced by the presence of Reed-Sternberg cells positive for CD30 and CD15 and negative for CD3, CD20, and CD45. She achieved complete remission after combination chemotherapy. Two years later, she noticed a red papule on her public area without any lymph node involvement. The biopsy specimens showed diffuse proliferation of large-sized atypical lymphoid cells positive for CD30 and CD45, and negative for CD3, CD20 and CD15. These findings were mostly compatible with CD30 (Ki-1)-positive anaplastic large cell lymphoma (Ki-1 lymphoma). Our case is considered to be cutaneous Ki-1 lymphoma preceded by Hodgkin's disease.

Clinical and immunohistochemical studies of skin eruptions: relationship to administration of interferon-alpha.

We observed transient, erythematous skin eruptions in 6 patients during the intravenous administration of interferon (INF)-alpha for chronic active hepatitis C. The eruptions appeared 5 to 14 days (mean: 6.8 days) after initiating its administration. They were localized or disseminated and consisted of edematous, erythematous, and/or papular changes. Vesicles and petechiae also appeared in some cases. The eruptions disappeared in 10 to 14 days, despite the continuance of INF-alpha and without specific treatment. Histological examination obtained from skin eruptions revealed perivascular infiltration of lymphoid cells, the majority which were CD4-positive, of the upper dermis. Edematous changes were present in the papillary dermis. Vascular endothelial cells in the upper dermis expressed both intercellular adhesion molecule-1 (ICAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1), while the epidermal keratinocytes produced neither. These findings suggested a nonallergic mechanism for such eruptions.

Hyperthermic effects in vitro on the peripheral lymphocytes isolated from three cases of malignant lymphoma/leukemia.

We have carried out in vitro studies of hyperthermic effects on the viability, blastogenesis, and ultrastructural changes of atypical lymphocytes isolated from the peripheral blood of three patients with malignant lymphoma/leukemia. One was lymphocytic lymphoma/leukemia (T-cell origin), and the others were adult T-cell lymphoma/leukemia (both acute and smoldering type). In the cases of adult T-cell lymphoma/leukemia, the peripheral lymphocytes were found to be more sensitive to hyperthermia than those of non-ATL patients in terms of trypan-blue exclusion ability and blastogenesis ability with concanavalin A challenge. When heated under sublethal conditions, lymphocytes of both ATL and non-ATL patients exhibited the following characteristics: production of multilayered nuclear membranes, increase in vesicles (lysosomes), swelling of mitochondria, and cytoplasmic vacuolization.

[Semi-malignant pitch-acanthoma on the hand of a coke oven worker].

We experienced a case of pitch-acanthoma which had developed on the hand of a coke worker after 15 years from his retirement. The patient was a 75-year-old male, who had worked mainly as a coke-oven worker for 24 years. In the spring of 1988, after 15 years from his retirement, he noticed a small nodule on the dorsal aspect of his right hand. He visited our clinic on June 1988 because the nodule was rapidly growing larger. The diagnosis of pitch-acanthoma was obvious from his occupational history and the characteristic poikilodermatous outlook of his skin. The tumor was removed surgically. Histological examination showed hyperkeratosis and acanthosis with horn-pearl formation. Moreover, a pack of atypical cells was observed within the lesion, suggesting an early malignant change. The patient was heavily exposed to a tar-gas-containing atmosphere in his workplace for quite a long period. As tar or pitch remains within the skin in spite of careful cleansing, workers in this atmosphere have a relatively high risk of developing skin cancer. Our present case shows that such malignant change can occur after long years and we would emphasize the necessity of a long term follow-up, perhaps throughout the lifetime of these workers.

[Electron microscopic observations of the conjunctiva in epidermolysis bullosa hereditaria].

A 35-year-old female had been clinically diagnosed as having epidermolysis bullosa hereditaria since her skin formed blisters from the time of her birth. Her left and right corneas become clouded at the age of 17 and 31 years, respectively. She was diagnosed as having bilateral secondary glaucoma at the age of 31 years and was medicated with antiglaucoma drugs. When examined by us, both corneas were invaded by conjunctival tissues and intraocular pressure in both eyes was 38 mmHg. Visual acuity was 0.09 (n.c.) in the right eye and she had no light perception in the left eye. A trabeculectomy OD was performed at our hospital. For confirmatory diagnosis, a pathological examination of the conjunctival and dermal tissues was done. Electron microscopic study demonstrated blister formation beneath the basal lamina and lost anchoring fibrils of both tissues. This finding confirmed that she had a receive form of dystrophic epidermolisis bullosa. This is a rare case of dystrophic epidermolisis bullosa with severe corneal changes and glaucoma diagnosed from electron microscopic observations.

[Evaluation of dermatological symptoms of Yusho patients in the annual examination in 1999-2000].

We analyzed the severity grades of the skin symptoms of Yusho patients who visited the annual examinations in 1999 and 2000. The severity grades of the skin symptoms clearly improved. The patients graded as 0 increased and those graded as II.III-III or III.IV-IV decreased as compared to the data in 1993. The pattern of the skin severity scores did not change much, although the patients who showed 0.1 reached 68% in 2000. The blood PCB concentration of Yusho patients also clearly decreased, especially in the patients who showed "A" pattern. Furthermore, the skin changes of the aged patients should be analyzed in detail in the future.

Malignant Triton tumor. A case with protean histopathological patterns.

A case of malignant Triton tumor occurring in the leg of a 48-year-old woman with neurofibromatosis (von Recklinghausen's disease) is presented. The neoplasm was composed mainly of spindle-shaped cells forming interlacing fascicles with areas of massive necrosis. The important feature in this neoplasm was the presence of rhabdomyoblastic cells admixed with other cellular components. In addition, variable histologic features including solid, myxomatous, hemangiomatous, hemangiopericytomatous, epithelioid, and lymphomatous areas were identified. This variety has been recognized in malignant schwannomas, but not in malignant Triton tumors. There were discrete foci with each predominant histologic feature shown in a map of the neoplasm in which the distribution of those components is demonstrated based on the histology and immunohistochemistry. Satisfactory biopsy specimens are necessary for accurate diagnosis of malignant Triton tumor.

Myofibroblasts in fibromatoses. An electron microscopic study.

Fifteen cases of fibromatoses were analyzed by electron microscopy, the objective being to compare the incidence and frequency of myofibroblasts in each category. Myofibroblasts were identified in all 15 cases and a considerably large number of these cells appeared in palmar fibromatosis, plantar fibromatosis, and nodular fasciitis. In keloid and cicatricial fibromatosis, however, only a small number of these cells were evident. In seven cases of extra-abdominal desmoid fibromatosis, the frequency of myofibroblasts in the component cells ranged from 10% to 64%, with a mean of 30%. The frequency was high in hypercellular lesions and low in hypocellular lesions, assuming that it would be roughly in parallel to the cellularity of the lesion in extra-abdominal desmoid fibromatosis and in other fibromatoses as well. There appeared to be no particular correlation between the number of myofibroblasts and recurrence of the lesion.