Acral melanoma in association with melanocytic naevus.
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Biomedical subjects
Publications and source records attributed to T Saida.
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Because malignant melanoma is a highly malignant neoplasm, correct diagnosis and appropriate treatment are essential to improve the prognosis. In the present paper the author summarizes the advancements in the therapy of malignant melanoma, reviewing papers recently published in this field. It is noteworthy that a narrow excision margin has been recommended even for the surgery of this neoplasm. This narrow margin has been approved by the prospective randomized trial performed by the WHO melanoma study group. The study group also confirmed that elective lymph node dissection is not significant in the improvement of the prognosis, when compared to the delayed lymph node dissection. Considering these findings, the author proposes a revised guideline for the treatment of malignant melanoma according to UICC stages. A brief comment is made on a new drug, fotemustine, that has an effect on brain metastases. In addition, high response rates obtained by the Dartmouth regimen (BCDT regimen), including tamoxifen, an estrogen antagonist, are reported. "Sequential" biochemoimmunotherapy based on a new concept of rational combination of chemotherapeutic and biologic agents seems highly effective against metastatic melanoma, showing more than 50% response rates. In the regimens, chemotherapy including CDDP is followed by administration of the cytokines, IL-2 and IFN-alpha. These regimens possibly induce specific and/or non-specific immune reactions against melanoma cells, which may contribute to the high response rates.
Galactocerebroside (Gc) is a major component of myelin in both the peripheral and central nervous systems. Although it is regarded as an important glycolipid hapten of myelin in rabbit experimental allergic neuritis (EAN), its role in human demyelinating diseases is not known. We studied three post-infectious encephalitis (PIE) patients related to Mycoplasma pneumoniae infection. All three of three patients with encephalitis and M. pneumoniae infection were positive for Gc antibodies (100%), while 25% of 32 M. pneumoniae-infected patients without neurological disease were positive, and 3.8% of 52 healthy controls. This indicates anti-Gc antibody is induced by M. pneumoniae infection. One of the PIE patients, who had extraordinary high titer antibody to Gc, showed an extensive, diffuse white matter demyelination and poor recovery. Since circulating anti-Gc antibody induces central nervous system demyelination in animals with elevated antibody titers and disruption of the blood-brain barrier, anti-Gc antibody may have an important function in the increased demyelination in PIE patients after M. pneumoniae infection.
A molecular typing approach for Campylobacter jejuni was applied with restriction fragment length polymorphism (RFLP) analysis of a 702-bp PCR-amplified portion of the flagellin-A (flaA) gene. We analyzed a total of 179 strains, including 69 independent clinical isolates from diarrheic patients in Japan, 85 isolates in China, and 25 heat-stable (HS) serotype strains by Penner and Hennessy (1980) J. Clin. Microbiol. 12, 732-737). Six AfaI, seven MboI, and five HaeIII RFLPs were found in the 702-bp flaA segment from the 179 strains. Using a combination of these three enzymes, 25 separate RFLP groups were recognized. While 59 of 154 (38.3%) strains obtained in Japan and China were nontypeable by the HS antigenic scheme, all but two of 154 (98.7%) could be typed by RFLP typing. All 11 isolates of HS-19 strains, which are frequently isolated from Guillain-Barré syndrome (GBS) patients, showed an identical RFLP pattern (Cj-1), and Cj-1 consisted only of HS-19 strains. This suggests that the HS-19:Cj-1 strain is distinct among C. jejuni strains. This molecular typing method provides a rapid and reliable typing scheme for epidemiological studies of C. jejuni, and may also be useful for the analysis of C. jejuni subtypes from GBS patients.
It is well known that tumor-specific CTLs have a crucial role in the elimination of tumors and that different CTL populations recognize tumor antigens in MHC-restricted and MHC-unrestricted manners. We have established two alpha beta CTL clones that recognize melanoma antigens in both human lymphocyte antigen (HLA)-A2-restricted and HLA-unrestricted manners. Flow cytometry analysis showed that these CTL clones carry CD3, CD8, and alpha beta T-cell receptor (TCR) and express low levels of CD56. In contrast, these CTL clones do not express CD16, indicating that they do not contain natural killer cells. TCR analysis of these CTL clones using an anchored PCR method revealed that each clone carries a single alpha beta TCR. Both CTL clones contained the same Valpha and Vbeta gene segments although they carried different Jalpha and Jbeta gene segments. Taken together, these results confirm that CTL clones that carry a single alpha beta TCR recognize melanoma antigens in both HLA-A2-restricted and HLA-unrestricted manners. It is strongly suggested that the dual recognition of these CTL clones for the melanoma antigens is mediated by TCRs. The novel mechanism for antitumor immunity by these CTLs may be important in the effective elimination of tumors in vivo.
We cloned two rat cDNAs of brain basic helix-loop-helix factor 1 (BHF1). These have an identical coding region, contain 357 amino acids and exhibit 94.6% identity to MATH-2/NEX1 in the basic helix-loop-helix region. BHF1mRNAs are dominantly expressed in the brain particularly in the cerebellum, in the adult bovine, rat and mouse. Two shorter BHF1mRNAs (1.6 kb and 1.8 kb) were also detected in the mouse embryo, and these decreased in the developmental process. These results suggest that BHF1 may play important roles in cerebellum-specific functions and development of neurons.
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We present a case of primary malignant melanoma arising in the rectum of a 71-year-old woman who had presented with intermittent rectal bleeding following bowel movement 2 months previously. Digital and sigmoidoscopic examination of the rectum revealed a 3 x 2 x 1 cm exophytic tumor with a granular surface in the rectum 35 mm from the dentate line. No increased pigmentation was detected. Biopsy revealed degenerated mucosa accompanied by severe infiltration of inflammatory cells, but no malignant cells. The tumor and normal mucosa surrounding the tumor was excised 12 days after the biopsy. Light microscopy revealed the tumor to consist of malignant melanocytes and showed that the tumor was surrounded by normal mucosa. Immunohistochemical staining with antimelanoma antibody and HMB-45 substuntiated the diagnosis. Clinical and laboratory examination excluded the presence of melanoma at sites other than rectum. The patient refused an abdomino-perineal resection of the rectum and combination chemotherapy was performed. She died 18 months after the initial operation due to local recurrences and metastases to pelvic lymph nodes, liver, and lung.
A 74-year-old Japanese male patient with squamous cell carcinoma arising in an epidermal nevus is described. The patient had widespread warty lesions involving large parts of the body since infancy. Recently, a nodular lesion appeared on the middle part of his back and increased in size. Histologically, the nodule was diagnosed as squamous cell carcinoma and the warty lesion showed the features of epidermal nevus. The nodular lesion was totally excised and the skin defect was covered with split-thickness skin grafting. To the best of our knowledge, this is the 16th patient with malignant change of a verrucous epidermal nevus.
p16INK4 gene, which encodes a specific inhibitor of cyclin-dependent kinase 4 (CDK4), has been recently reported as an important tumour suppressor gene. It is mapped to chromosome 9p21, which is frequently deleted or mutated in many tumour cell lines including malignant melanoma. Since the CDK4/cyclin D complex propels a cell to go through the G1 check point of the cell cycle, a critical phase of cell division, alteration of the p16INK4 gene could lead a cell to uncontrolled proliferation and malignant transformation. To clarify any role for p16INK4 and CDK4 proteins in the development of human malignant melanoma, we have examined, immunohistochemically, the expression of these two proteins in melanocytic neoplasms including 19 primary lesions of non-familial melanoma. Intense nuclear and/or cytoplasmic expression of the CDK4 protein was observed in 11 of 19 cases (58%) of melanoma. In contrast, virtually no nuclear or cytoplasmic staining for CDK4 protein was detected in 28 benign melanocytic naevi, including six Spitz naevi. Expression of p16INK4 protein was observed in three of 19 melanomas (16%) and in 17 of 28 benign naevi (61%). Inverse expression of CDK4 and p16INK4, at individual cell level, was detected in one case of melanoma. The present study suggests that CDK4 overexpression is characteristic for malignant melanoma, and probably reflects its autonomous accelerated cell proliferation. The expression rate of p16INK4 protein in malignant melanoma was lower than that in benign naevi, although the significance of p16INK4 deletion in melanoma development has not been definitely confirmed.
Human T lymphotropic virus type I (HTLV-I) is a human retrovirus etiologically linked to Adult T cell leukemia (ATL) and HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although most HAM/TSP patients have high anti-HTLV-I antibody titers in their sera, HTLV-I infected but seronegative patients with neurological diseases have been reported. To clarify whether seronegative, HTLV-I related neurological disease may exist, we have developed a method that measures the production of interleukin-2 (IL-2) from HTLV-I synthetic peptide-stimulated peripheral blood lymphocytes (PBL) of HTLV-I infected persons. This method is sensitive enough to detect exposure to HTLV-I before seroconversion or even before detection by PCR. We examined 12 patients with chronic progressive myelopathy and eight patients with multiple sclerosis (MS) in central Japan, where the prevalence rate of HTLV-I is between one and four percent among asymptomatic blood donors, using the IL-2 production assay. None of them were positive by the assay, suggesting seronegative HTLV-I myelopathy is very rare among patients with chronic progressive myelopathy and MS in Japan.
High titers of anti-GM1 ganglioside antibodies (anti-GM1 antibodies) may be implicated in lower motor neuron disease. We studied the pathogenic role of anti-GM1 antibody using the petroleum jelly-gap voltage clamp technique on isolated single myelinated rat nerve fibers. Anti-GM1 antisera were obtained from rabbits immunized with GM1 ganglioside. Extracellularly applied anti-GM1 antisera without complement activity increased both the rate of rise and the amplitude of the K+ current elicited by step depolarization, with little effect on Na+ current. In the presence of active complement, however, anti-GM1 antibodies decreased the Na+ current, and caused a progressive increase of nonspecific leakage current. Neither complement alone nor complement-supplemented antisera from which anti-GM1 antibodies were depleted by affinity chromatography had any effect on ionic current. These observations indicate that anti-GM1 antibodies themselves can uncover K+ channels in the paranodal region, while anti-GM1 antibodies bound to the nodal membrane in the presence of complement may form antibody-complement complexes that block Na+ channels and disrupt the membrane at the node of Ranvier.
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 Bowen's disease (5/5 specimens) and thermal keratosis (2/3). In contrast, no definite neoplastic cells were found in two grafts from extramammary Paget's 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.
The alpha subunit of guanine nucleotide-binding protein Go (Go alpha), which was initially isolated from bovine brain, interacts with muscarinic cholinergic receptors and regulates neuronal calcium channels. Go alpha is known to be localized in neural tissues, some endocrine cells, and neuroendocrine tumors. We have immunohistochemically investigated the expression of Go alpha in 4 cases of Merkel cell carcinoma using the method of microwave treatment. In all cases of Merkel cell carcinoma, Go alpha was consistently detected on the plasma membrane and cytoplasm of the tumor cells. Nerve fibers in the skin were also positive for Go alpha, but other epidermal or dermal components such as keratinocytes, melanocytes, fibroblasts, or lymphoid cells were negative. Tumor cells of squamous cell carcinoma, cutaneous lymphoma, sweat gland carcinoma, and malignant melanoma were negative for Go alpha. The present study indicates that Go alpha may be a useful immunohistochemical marker of Merkel cell carcinoma.
Leber's hereditary optic neuropathy (LHON), a maternally inherited disease causing severe bilateral visual loss in young men, is linked to 12 point mutations in mitochondrial DNA, the most common of which is at the nucleotide position 11778. The 11778 point mutation has also been detected in several patients with possible multiple sclerosis (MS), especially women with severe visual loss in both eyes. Because frequent and severe optic neuropathy is a feature of MS in Japan, we screened 80 Japanese MS patients for the presence of the 11778 mutation by mutation-specific polymerase chain reaction. Eighteen women with MS had bilateral optic neuropathy, but none had the mutation at 11778. There is no association between Japanese MS and the 11778 mitochondrial DNA mutation.
BACKGROUND AND DESIGN: In vivo epiluminescence microscopy is now used as a useful noninvasive method for determining clinical diagnosis of pigmented skin lesions. Until now, however, pigmented lesions on the volar skin have been hardly studied with this method. In the present epiluminescent study, various kinds of pigmented lesions on the volar skin were extensively investigated by means of video macroscope, a newly developed electronic device with a higher magnification power, and correlation between the magnified features and histopathologic findings was evaluated. RESULTS: Magnified features of most lesions of acquired or congenital melanocytic nevus on the volar skin were classified into the following three typical patterns: (1) a parallel pattern formed by pigmented parallel lines corresponding to the furrows of the skin markings, (2) a latticelike pattern composed of pigmented lines along and across the furrows of the skin markings, and (3) a fibrillar pattern formed by densely packed, fibrillar pigmented lines arranged in the direction crossing the furrows. In contrast, macular or plaque portions of acral lentiginous melanoma exhibited disorderly arranged, irregular pigment patterns, mainly affecting the ridges of the skin markings. In addition, brown globules of various shades and many black dots of variable sizes were often observed and, on the margin of the lesions, pseudopods and/or the "serrated" pattern were detected. Cutaneous hemorrhagic macule and so-called black heel showed highly specific features and thus could be easily diagnosed with video macroscopy. CONCLUSION: Video macroscope proved to be a very useful instrument for the diagnosis of pigmented lesions on the volar skin.
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