Congenital nevi with hypomelanosis and fine scales.

BACKGROUND: Nevus is a hamartoma or malformation of one or more skin components, resulting in aberrant differentiation of the cell lineage(s) mostly during developmental stages. Although multiple lineages may be involved in a nevus, the combination of melanocyte and keratinocyte abnormalities has been rarely discussed. OBJECTIVES: To present two cases of congenital nevi with hypomelanosis and superficial fine scales. MATERIALS & METHODS: Skin specimens of the patients were analysed by immunohistochemistry and electron microscopy. RESULTS: Morphological and immunohistochemical studies indicated aberrant epidermal differentiation in the lesional skin specimens. Electron microscopy showed defective melanosome maturation in the melanocytes of the nevi samples. CONCLUSION: These results demonstrate that both epidermal and melanocytic lineages can concomitantly contribute to the formation of a nevus lesion.

Intestinal Bacterial Infection Diagnosed by Histological Examination of Endoscopic Biopsy Specimens.

Intestinal spirochetosis (IS) in humans is characterized by spirochetal microorganisms attached to the luminal surface of the colonic epithelium. In the present case, attached organisms appeared as 3- to 4 µm-thick (average thickness, 3.4 µm) basophilic fringes or haze in HE-stained endoscopic biopsy specimens. The basophilic fringes were clearly labeled by Treponema pallidum antiserum. Because IS is relatively rare in developed countries, thin basophilic fringes characteristic of IS are readily overlooked. Thus, the recognition of histological characteristics of this disease is important for its diagnosis.

Effects of Dietary Xanthophylls, Canthaxanthin and Astaxanthin on N-Methyl-N-nitrosourea-induced Rat Mammary Carcinogenesis.

BACKGROUND: Natural xanthophylls, canthaxanthin and astaxanthin are known to exhibit anticancer activity. However, the dietary effects of canthaxanthin and astaxanthin on N-methyl-N-nitrosourea (MNU)-induced mammary cancer remain controversial, and their mechanisms of action have not been clearly identified. MATERIALS AND METHODS: Three-week-old female Sprague-Dawley rats were fed a xanthophyll-free (basal diet) diet or experimental diets containing canthaxanthin or astaxanthin (0.04% and 0.4%) for 5 weeks (until 8 weeks of age), after which all rats were provided the basal diet (n=15 each). Rats were administered MNU at 6 weeks of age, and the incidence of mammary tumors at 20 weeks of age was compared. The expression of adiponectin in mammary adipose tissues taken at 7 weeks of age was also compared. RESULTS: Compared to the basal diet group, the 0.4% (but not the 0.04%) astaxanthin diet significantly reduced the incidence of palpable mammary carcinoma (92% vs. 42%; p<0.05), while the low and high canthaxanthin diets produced no significant inhibition. Adiponectin immunoblotting showed significantly higher expression in the 0.4% astaxanthin diet group, while the other groups were similar to the basal diet group. CONCLUSION: High concentrations of astaxanthin suppress MNU-induced mammary carcinoma. Changes in adiponectin may be involved in the mechanism of action.

Keratin 19-positive cutaneous squamous cell carcinoma with elevated serum cytokeratin 19 fragment 21-1 level: A case report.

cytokeratin 19 fragment 21-1 (CYFRA21-1) is a marker of lung cancer useful for evaluating clinical diagnosis and prognosis. To the best of our knowledge, there have been no reports of cutaneous squamous cell carcinoma (SCC) with high levels of CYFRA21-1 to date. We herein report a case of a 79-year-old man with a large subcutaneous tumor of the left shoulder, which was diagnosed as primary cutaneous poorly differentiated SCC. The tumor nests were composed of poorly differentiated atypical squamous cells exhibiting high-grade malignancy and mitotic figures; multinuclear cells were also identified inside lymph vessels. Keratin 19 (K19) was intensely expressed in tumor cells. A significantly elevated level of CYFRA21-1 (33 ng/ml) was observed preoperatively. After surgery, the level of CYFRA21-1 was significantly decreased (from 33 to 5.0 ng/ml). Our case demonstrated that K19-positive primary cutaneous undifferentiated SCC induced high levels of CYFRA21-1 in the serum. Thus, CYFRA 21-1 may be a marker indicative of poorly differentiated cutaneous SCC exhibiting K19 expression.

N-methyl-N-nitrosourea-induced schwannomas in male Sprague-Dawley rats with a literature review of inducible and spontaneous lesions.

N-methyl-N-nitrosourea (MNU) possesses peripheral nervous system carcinogenic activity in rats and induces benign and malignant schwannomas in systemic organs. In this retrospective study, we compared the characteristics of various immunohistochemical markers in MNU-induced schwannomas in male Crj:CD(SD)IGS rats including: vimentin (Vim), S100, p75 nerve growth factor receptor (LNGFR), CD57, pancytokeratin (CK), myoglobin, desmin and α smooth muscle actin (SMA). Single intraperitoneal exposures of 50 or 75mg/kg MNU in male rats at the age of 4 weeks induced schwannomas in 43 surviving and terminated rats up to 30-weeks-old. The incidence rate of neoplastic lesions was 37% (16 of 43 rats). Benign schwannomas (mesentery, pancreas, thymus) and malignant schwannomas (subendocardium, cardiac intramural, thoracic cavity, abdominal cavity, prostate), occurred in nine and seven rats, respectively. All neoplastic lesions were moderately or strongly positive for Vim, S100 and LNGFR proteins. Benign tumors were weakly positive and malignant tumors strongly positive for Ki-67, suggesting a high active proliferation rate of Schwann cell precursors. All lesions were negative for CD57, CK, myoglobin, desmin and SMA. This data may provide useful immunohistochemical information for the investigation of schwannomas in rat chemical carcinogenicity studies.

Autopsy results of a case of ingestion of sodium hydroxide solution.

Sodium hydroxide is a strongly corrosive alkali. We describe herein a case of suicide by ingestion of sodium hydroxide. A man in his 80s was found dead with a mug and a bottle of caustic soda. Macroscopically, liquefaction and/or disappearance of esophagus, trachea and lung tissue and a grayish discoloration of the mucosa of the stomach were seen along with blackish brown coloration of the skin, mouth, and oral cavity. The contents of the gastrointestinal tract showed a pH level of 7-8 on pH indicator strips. Histopathologically, liquefactive necrosis of remnant lung tissue and the stomach were seen. As biological reactions such as vasodilatation and inflammation were not detected in these organs, only a short number of hours must have passed between ingestion and death. This human case provides valuable information concerning the direct irritation induced by systemic exposure to corrosive substances.

A spontaneously occurring malignant ovarian Sertoli cell tumor in a young Sprague Dawley rat.

Primary ovarian tumors are generally uncommon in rats used in toxicologic studies. A malignant Sertoli cell tumor was present in the ovary of a 19-week-old female Sprague Dawley rat. Macroscopically, the mass was white and firm, 10 × 13 × 17 mm in size, and located in the right ovary. Histopathologically, the mass was composed of nests of pleomorphic cells, which formed seminiferous-like tubules separated by a thin fibrovascular stroma. The tubules were lined by tumor cells, which had basally located nuclei and abundant eosinophilic and vacuolated cytoplasm. In some areas, the tumor cells were arranged in a retiform growth pattern, mimicking a rete testis/ovarii. Disseminated metastases to the surfaces of the mesentery, spleen and liver were also present. Immunohistochemically, many tumor cells were strongly positive for vimentin, estrogen receptor α and Ki 67. Some tumor cells were positive for pancytokeratin and inhibin α. These findings closely resemble those of an ovarian-derived human malignant Sertoli cell tumor. From our review of the literature, we believe this is the first report of a spontaneous malignant Sertoli cell tumor in the ovary of a young laboratory rat. This case might provide useful historical control information for rat toxicity studies.

Green tea extract attenuates MNU-induced photoreceptor cell apoptosis via suppression of heme oxygenase-1.

The effects of green tea extract (GTE) on N-methyl-N-nitrosourea (MNU)-induced photoreceptor cell apoptosis were examined, and the possible mechanisms of action of GTE were assessed. Alterations in the retinal morphological architecture were determined by hematoxylin-eosin staining, vimentin immunoreactivity, and photoreceptor cell apoptosis (TUNEL labeling). Expression of oxidant marker, heme oxygenase (HO)-1, mRNA levels in outer nuclear cells was assessed by laser capture microdissection (LCM). Sprague-Dawley rats were given 40 mg/kg MNU at 7 weeks of age in the absence and presence of 250 mg/kg GTE treatment (once daily from 3 days prior to MNU for a maximum 10 days). Although photoreceptor cell degeneration began 24 hr after MNU, the morphological effects of GTE at the time point were not definitive. However, GTE lowered TUNEL labeling and HO-1 mRNA expression. At 7 days after MNU, photoreceptor damage was attenuated by GTE treatment. Therefore, the ability of GTE to reduce MNU-induced photoreceptor cell apoptosis may be due to its antioxidant properties.

Susceptibility to N-methyl-N-nitrosourea-induced retinal degeneration in different rat strains.

To evaluate the potential role of genetic background in the susceptibility to retinal degeneration induced by N-methyl-N-nitrosourea (MNU), female rats of the Sprague-Dawley (SD), Long-Evans (LE) and Copenhagen (CH) strains were administered 50 mg/kg MNU or saline at 7 weeks of age. Retina morphology and morphometric analysis of all rats was performed 7 days after MNU administration. Atrophy of both the peripheral and central outer retina occurred in all rat strains exposed to MNU. Decreased photoreceptor cell ratio and increased retinal damage ratio were observed. The severities of the retinal atrophy were similar among all three rat strains. In conclusion, MNU-induced photoreceptor degeneration developed consistently in all three strains regardless of the absence (SD rats) or presence (LE and CH rats) of melanin in the retina, suggesting that genetic and melanin factors did not affect photoreceptor cell death after MNU.

Characterization of mammary adenocarcinomas in male rats after N-methyl-N-nitrosourea exposure--Potential for human male breast cancer model.

The frequency of breast cancer in men is extremely rare, reported to be less than 1% and there is currently no available animal model for male mammary tumors. We compared the characteristics of various immunohistochemical markers in N-methyl-N-nitrosourea (MNU)-induced mammary adenocarcinomas in male and female Crj:CD(SD)IGS rats including: estrogen receptor α (ER), progesterone receptor (PgR), androgen receptor (AR), receptor tyrosine-protein kinase erbB-2 (HER2), GATA binding protein 3 (GATA3), and proliferating cell nuclear antigen (PCNA). Female mammary adenocarcinomas were strongly positive in the nuclei of tumor cells for PCNA and ER (100%) with only 60% and 53% expressing PgR and GATA3, respectively. 100% of male adenocarcinomas also exhibited strongly positive expression in the nuclei of tumor cells for PCNA, with 25% expressing AR and only 8% showing positivity for ER. Male carcinomas did not express PgR or GATA3 and none of the tumors, male or female, were positive for HER2. Based on the observed ER and PgR positivity and HER2 negativity within these tumors, MNU-induced mammary adenocarcinomas in female rats appear to be hormonally dependent, similar to human luminal A type breast cancer. In contrast, MNU-induced mammary adenocarcinomas in male rats showed no reactivity for ER, PgR, HER2 or GATA3, suggesting no hormonal dependency. Both male and female adenocarcinomas showed high proliferating activity by PCNA immunohistochemistry. Based on our literature review, human male breast cancers are mainly dependent on ER and/or PgR, therefore the biological pathogenesis of MNU-induced male mammary cancer in rats may differ from that of male breast cancer in humans.

Spontaneously occurring lymphohematopoietic tumors in three young Sprague Dawley rats.

To assess the toxicological and pharmacological effects of chemicals, it is important to know what kinds of neoplasms naturally occur in the early life of laboratory animals. In the present study, we identified three spontaneous hematopoietic tumors in three of 52 young female Sprague-Dawley rats used in a pharmacological study. These cases included two rats (Case 1 and 2) from a sesame oil-treated group and one rat (Case 3) from a chemical-treated group in the same single gavage study. Case 1 rapidly lost body weight at 13 weeks of age without any clinical signs and died. Round lymphoid tumor cells were found in the spleen, liver, bone marrow, and pancreas. The tumor cells were immunohistochemically positive for CD3 and PCNA, which is suggestive of malignant T-cell lymphoma. Cases 2 and 3 had rapid body weight loss at 14 and 16 weeks of age, respectively, exhibited severe anemia, hypolocomotion, and decreased body temperature, and were euthanized due to a poor prognosis based on severe clinical signs. Pleomorphic large tumor cells were found in the spleen, liver, bone marrow, lymph nodes, heart, kidneys, lung, pancreas, adrenal glands, pituitary gland, ovaries, Harderian gland, and/or eyes. The tumor cells were immunoreactive for CD34, lysozyme, and PCNA, which is suggestive of myeloid leukemia. These cases might provide useful historical control information for rat toxicity studies.

Dietary effects of mead acid on N-methyl-N-nitrosourea-induced mammary cancers in female Sprague-Dawley rats.

The effect of mead acid (MA; 5,8,11-eicosatrienoic acid) on the suppression of the development and growth of N-methyl-N-nitrosourea (MNU)-induced mammary cancer in female Sprague-Dawley rats was examined. The MA diet (2.4% MA) or control (CTR) diet (0% MA) was started at 6 weeks of age, MNU was injected intraperitoneally at 7 weeks of age, and the rats were maintained on the respective diets for the whole experimental period (until 19 weeks of age). All induced mammary tumors were luminal A subtype carcinomas (estrogen and progesterone receptor positive and HER2/neu negative). The MA diet significantly suppressed the initiation and promotion phases of mammary carcinogenesis; MA suppressed the development (incidence, 61.5 vs. 100%; multiplicity, 2.1 vs. 4.5) and the growth (final tumor weight, 427.1 vs. 1,796.3 mg) of mammary cancers by suppressing cell proliferation, but not by accelerating cell death. There were evident changes in the major fatty acid composition of n-3, n-6, and n-9 fatty acids in the serum of the MA diet group; there was a significant increase in MA and significant decreases in oleic acid (OA), linoleic acid, arachidonic acid and docosahexaenoic acid. In non-tumorous mammary tissue, there was a significant increase in MA and a significant decrease in OA in the MA diet group. The n-6/n-3 ratios in serum and mammary tissue of the MA diet group were significantly decreased. The MA diet suppressed MNU-induced luminal A mammary cancer by lowering cancer cell proliferation. Therefore, MA may be a chemopreventive and chemotherapeutic agent. In addition to hormone therapy, MA supplementation may be a beneficial chemotherapeutic agent for the luminal A subtype of breast cancer.

Cutaneous Epithelial Lesions Induced by N-Methyl-N-nitrosourea in Male Sprague-Dawley Rats: A Possible Animal Model for Human Keratoacanthoma.

A single intraperitoneal injection of 50 or 75 mg/kg N-methyl-N-nitrosourea in male Sprague-Dawley rats at 4 weeks of age, dose-dependently resulted in cutaneous epithelial cysts and tumors of pilosebaceous origin. Cysts were composed of epidermal cysts or mixed epidermal and inner root sheath hybrid cysts. The majority of induced tumors were keratoacanthomas. A few tumors were trichofolliculomas, trichoblastomas, pilomatricomas, or sebaceous adenomas. All tumors were benign pilosebaceous tumors. Keratoacanthomas were crater-shaped tumors with thick infoldings of epithelium containing keratohyalin granules (epidermal lip) that abruptly changed to epithelium containing trichohyalin granules. The morphological similarity and resemblance of keratin 1, 10, and 14 profiles, and p63 and ß-catenin expression between mixed epidermal and inner root sheath hybrid cysts and keratoacanthomas suggests that hybrid cysts progressed to keratoacanthomas, and the cells from infundibular cells to inner root sheath cells of the pilar segment seem to be the origin of rat keratoacanthomas. Immunohistochemical localization of keratins 1, 10 and 14, p63, and ß-catenin in trichofolliculoma, trichoblastoma, and pilomatricoma, as well as keratoacanthoma, may indicate tumor histogenesis.

Autopsy report for chemical burns from cresol solution.

Cresol, which is used as a disinfectant and insecticide, has erosive effects on epidermal and epithelial tissues in the body. Oral exposure causes gastrointestinal corrosive injuries as a direct chemical burn. We report herein a case of suicidal poisoning by ingestion of cresol solution. An octogenarian man with depression was found dead approximately 14 h after exposure to less than 500 mL of saponated cresol solution. Macroscopically, corrosive lesions such as red-to-brown-colored epithelium and edematous thickening of walls were seen in the skin, mouth, oral cavity, esophagus, and stomach. Histopathologically, coagulative necrosis and vascular dilatation were detected from mucosal to muscular layers in the esophagus, stomach, and duodenum. Congestive edema of the lungs, edematous changes in the brain, and proximal tubular necrosis of the kidneys were seen, suggesting acute circulatory disturbance due to shock. This human case offers valuable information on the direct irritation and shock induced by systemic exposure to corrosive substances.

The role of CD5 expression in thymic carcinoma: possible mechanism for interaction with CD5+ lymphoid stroma (microenvironment).

AIMS: Most thymic carcinomas express the lymphocyte marker CD5 aberrantly. This study was performed to examine the role of the self-reactive CD5 antigen in thymic carcinoma. METHODS AND RESULTS: We examined CD5 expression in thymic carcinoma in relation to the lymphoid stroma. All cases of thymic carcinoma examined expressed CD5. A number of CD5(+) lymphocytes were also present in the stroma of thymic carcinoma. The CD5(+) tumour areas were predominantly in contact with the lymphoid stroma, and the expression level was significantly lower in tumour cells than lymphocytes. Although p53 and Bcl-2 expression levels were significantly higher in thymic carcinoma than normal thymic epithelial cells (TECs), they did not differ between CD5(+) and CD5(-) areas. E-cadherin expression in thymic carcinoma was comparable with that of normal TECs, and it also did not differ between these areas. In contrast, both Ki-67 index and mitotic activity were significantly higher in thymic carcinoma than normal TECs, and they were significantly higher in CD5(+) than CD5(-) areas. CONCLUSIONS: CD5 may be induced by interaction with CD5(+) lymphoid stroma, and may be related to tumour proliferation. CD5 induction may also be a significant and/or specific effect of the tumour microenvironment of the thymus.

Milia may originate from the outermost layers of the hair bulge of the outer root sheath: A case report.

It has been hypothesized that milia originate from the hair bulge of the outer root sheath. To elucidate the histogenesis of milia, an immunohistochemical study was performed using anti-keratin and anti-filaggrin antibodies to determine the levels of keratin and filaggrin expression. Keratin expression was evaluated using anti-keratin antibodies against K1, K7, K8, K10, K14, K15, K16, K17, K18, K19 and K20. K1 and K10 expression were detected in the suprabasal layers of the more superficial section of the cyst walls, but not in the deeper section of the cyst walls. However, K14 and K17 were expressed in all layers of the cyst walls. Notably, K15 was expressed in the outermost layer of the deeper section of the cyst walls and hair germ structure, whereas filaggrin was expressed in the superficial layer of the more superficial section of the cyst walls. Therefore, the pattern of keratin and filaggrin expression indicates that milia may originate from the outermost cells of the hair bulge of the outer root sheath.

Romanowsky staining using liquid-based cytology: A pilot study using Cytolyt(®)/HESPANDER(®) processing solution for ThinPrep(®) preparations.

BACKGROUND: Liquid-based cytology (LBC) has been used to prepare and examine many types of samples. However, the use of Romanowsky stains for LBC has not yet been evaluated. Herein, we report a technique for the use of the Romanowsky May-Grünwald-Giemsa (MGG) stain using a ThinPrep(®) preparation technique (MGG-LBC). METHODS: KPL-1 breast cancer cells at a density of 1.25 × 10(5)/20 ml were compared in conventional smear and MGG-LBC preparations. Cell size, nucleus/cytoplasm (N/C) ratio, and morphological findings were investigated. Clinical samples including voided urine and pleural effusion were also examined in MGG-LBC preparations. RESULTS: Cellularity appeared lower with MGG-LBC compared with Papanicolaou-stained smears using the ThinPrep(®) method, though the cell size and N/C ratio showed similar tendencies. Reactive mesothelial cells, normal urothelial cells, urothelial carcinoma cells, crystals, and bacteria were all clear enough for diagnostic purposes after MGG-LBC. CONCLUSION: Romanowsky staining is necessary for the cytodiagnosis of some conditions. MGG-LBC may contribute to the cytodiagnostic results using LBC preparations.

Sclerosed Hemangioma Accompanied by Multiple Cavernous Hemangiomas of the Liver.

BACKGROUND: A sclerosed hemangioma of the liver, an extremely rare type of benign hepatic tumor, was found at autopsy. CASE REPORT: An 81-year-old Japanese man was admitted to our hospital for surgical resection of squamous cell carcinoma of the skin in his left forearm. At admission, serological tests for hepatitis B surface antigen and hepatitis C antibody were negative with no evidence of cirrhosis. At 2, 3, and 5 months after the removal of the forearm tumor, skin grafting was performed because of unhealed skin ulceration. Although anti-bacterial drugs were prescribed, the patient died after the 3rd skin graft (5 months after the surgery) because of pneumonia. During the treatment course, the patient was diagnosed as having multiple liver masses suspected to be cysts of the liver based on non-contrasted computed tomography results. Autopsy revealed a sclerosed hemangioma occupying the entire left lobe accompanied by multiple small cavernous hemangiomas in the right lobe of the liver. CONCLUSIONS: Sclerosed hemangioma, a rare benign disease, occurred in association with degeneration and sclerosis of cavernous hemangiomas of the liver. The VEGF pathway may be involved in the genesis of cavernous and sclerosed hemangioma of the liver.

Mead acid supplementation does not rescue rats from cataract and retinal degeneration induced by N-methyl-N-nitrosourea.

Fatty acids and their derivatives play a role in the response to ocular disease. Our current study investigated the effects of dietary mead acid (MA, 5,8,11-eicosatrienoic acid) supplementation on N-methyl-N-nitrosourea (MNU)-induced cataract and retinal degeneration in Sprague-Dawley rats. Experiment 1 was designed to inhibit cataract formation, with the dams fed a 2.4% MA or basal (<0.01% MA) diet during lactational periods. On postnatal day 7, male pups received a single intraperitoneal (ip) injection of 50 mg/kg MNU or vehicle. Lens opacity and morphology were examined 7 and 14 days after the MNU injection. Experiment 2 was designed to inhibit retinal degeneration and was performed with female postweaning rats. In this experiment, dams were fed the 2.4% MA or basal diet during the lactational periods. Thereafter, the female pups were continuously fed the same diets during their postweaning periods. On postnatal day 21 (at weaning), pups received a single ip injection of 50 mg/kg MNU. Retinal morphology was examined 7 days after the MNU injection. In experiment 3, six-week-old female rats were fed the 2.4% MA or basal diet starting at one week before the MNU injection and were then continuously fed the same diets until sacrifice. Rats at 7 weeks of age were given a single ip injection of 40 mg/kg MNU, and the retina was then examined morphologically one week after the MNU injection. In experiment 1, mature cataract was found in all of the MNU-treated groups, with or without MA supplementation. In experiments 2 and 3, atrophy of both the peripheral and central outer retina occurred in all rats exposed to MNU, with or without MA supplementation, respectively. The severities of the cataracts and retinal atrophy in the rats were similar regardless of MA supplementation. Dietary mead acid, which is used as a substitute in essential fatty acid deficiency in the body, does not modify MNU-induced cataract and retinal degeneration in rat models.

Leiomyomatosis peritonealis disseminata positive for progesterone receptor.

BACKGROUND: Leiomyomatosis peritonealis disseminata (LPD) is a rare condition that occurs in reproductive-age women. The pathogenesis of LPD is considered to be related to female sex hormones. CASE REPORT: A 30-year-old woman who had undergone an ovariectomy due to calcified thecoma at 24 years of age and had delivered a baby boy at 29 years of age showed abnormal abdominal-pelvic masses in a computed tomography scan. The peritoneal nodules were resected and histologically diagnosed as LPD. Smooth muscle cells in LPD lesions expressed progesterone receptor, while estrogen receptor and luteinizing hormone/chorionic gonadotropin receptor were negative. CONCLUSIONS: LPD should be considered when multiple nodules mimicking dissemination of malignancies are found in the abdominal cavity. In the present case, progesterone may have been involved in the pathogenesis of LPD.