The Study of Cutaneous Melanomas in Camargue‐Type Gray‐Skinned Horses (1): Clinical–Pathological Characterization

The clinical and pathological characteristics of cutaneous melanomas occurring in Camargue‐type gray‐skinned horses are reported. Examination of 83 tumor‐bearing horses revealed that the tumors occurred most frequently underneath the tail (93.9%) and at high rates in the peri‐anal region (43.0%), the lips (33.0%), and the eyelids (24.0%), but rarely in the vulva (3.8%). Tumorous lesions were characterized by the presence of either hemispheric nodules or large infiltrated plaques, or their combinations. Microscopic examination indicated that tumorous lesions were composed mostly of melanocytes and numerous melanophages and that component cells manifested a remarkable cellular atypia with anisocytosis and anisokarinosis. Pathological examination of lesions corresponding to earlier stages of the tumors disclosed that tumor formation and its related melanogenesis occurred in close topographical association with apocrine sweat glands, but not at the dermal–epidermal junction. Larger nodules of the tumors were often composed of a concentric deposition of cell layers, each being separated by dermal components from the epidermis. Because of the absence of their tropism toward the epidermis and their multiloculation, horse melanomas are considered to be different in their pathological characteristics from human melanomas.     

The study of cutaneous melanomas in Camargue-type gray-skinned horses (2): epidemiological survey

An epidemiological survey was made on cutaneous melanomas occurring in Camargue-type, gray-skinned horses in southern France. The population investigated was composed of 264 horses, which were selected from the Camargue horse stud registry and were allowed to be examined by the owners. The presence of tumors was inspected macroscopically according to the standardized protocols of veterinary medicine specialists, and some tumors were subjected to macroscopic histopathological examination. The results indicated that: 1) the prevalence of melanomas in the overall population was 31.4%; 2) the odds ratio was obtained for an age class of 5-9 years, in which most melanomas were presumed to occur; 3) the incidence of melanomas was significantly correlated with age, giving a prevalence of 67% at ages > 15 years; 4) the size and number of tumorous lesions were significantly related to age; 5) little correlation was observed between melanoma incidence and gender; and 6) the most frequently occurring body site of these tumors was underneath the tail. Because of their frequent occurrence in shaded body regions, sun exposure was not likely to be a risk factor for melanoma formation in these horses. In view of the slightly darker skin pigmentation in these horses at younger ages, the unique characteristics of their melanocytes may be associated with melanoma formation.     

The Study of Cutaneous Melanomas in Camargue‐Type Gray‐Skinned Horses (2): Epidemiological Survey

An epidemiological survey was made on cutaneous melanomas occurring in Camargue‐type, gray‐skinned horses in southern France. The population investigated was composed of 264 horses, which were selected from the Camargue horse stud registry and were allowed to be examined by the owners. The presence of tumors was inspected macroscopically according to the standardized protocols of veterinary medicine specialists, and some tumors were subjected to macroscopic histopathological examination. The results indicated that: 1) the prevalence of melanomas in the overall population was 31.4%; 2) the odds ratio was obtained for an age class of 5–9 years, in which most melanomas were presumed to occur; 3) the incidence of melanomas was significantly correlated with age, giving a prevalence of 67% at ages> 15 years; 4) the size and number of tumorous lesions were significantly related to age; 5) little correlation was observed between melanoma incidence and gender; and 6) the most frequently occurring body site of these tumors was underneath the tail. Because of their frequent occurrence in shaded body regions, sun exposure was not likely to be a risk factor for melanoma formation in these horses. In view of the slightly darker skin pigmentation in these horses at younger ages, the unique characteristics of their melanocytes may be associated with melanoma formation.     

Immunohistochemical study of pepsinogen C expression in cutaneous malignant melanoma: association with clinicopathological parameters

BACKGROUND: The aim of this study was to evaluate the pepsinogen C expression in malignant cutaneous melanomas and analyze its possible relationship to clinical and pathological parameters. Pepsinogen C is an aspartyl proteinase primarily involved in the digestion of proteins in the stomach and represents one of the main androgen-inducible proteins in breast cancer cells. METHOD: Tumoral pepsinogen C expression was retrospectively analyzed in 35 paraffin-embedded tissues from patients with primary malignant cutaneous melanoma and in 10 samples from 10 benign lesions (4 dermal melanocytic nevi, 4 compound melanocytic nevi and 2 dysplastic melanocytic nevi), using immunohistochemical methods. RESULTS: The benign lesions were consistently negative for pepsinogen C, whereas 20 of the 35 malignant melanomas (57%) showed positive immunostaining for pepsinogen C. The percentage of pepsinogen C-positive tumors was significantly higher in men than in women (p=0.01) and in epithelioid melanomas than in fusocellular or mixed type melanomas (p=0.003). In addition, the percentage of pepsinogen-C positive tumors was positively and significantly correlated with lesion thickness (p=0.003), Clark's level of invasion (p=0.028) and tumor stage (p<0.001). CONCLUSION: Pepsinogen C could be a new prognosticator of unfavorable outcome in cutaneous malignant melanoma.     

Anoplocephala perfoliata in Horses in Sweden: Prevalence,Infection Levels and Intestinal Lesions

Distal ileum, caecum and proximal colon of 470 horses were examined for helminths during 1 year at an abattoir in central Sweden. The infection levels of the horse tapeworm Anoplocephala perfoliata, their stage of development, site of attachment and gross pathological lesions caused by the worm were recorded. Faecal samples from 395 of the horses were examined specifically for tapeworm segments and eggs in order to correlate these findings with the numbers in the alimentary canal. In total 65% of the horses were infected with A. perfoliata and the mean intensity of infection was 79 worms per infected horse with a maximum of 912. The level of infection was significantly higher in (1) 3rd and 4th than in 1st and 2nd quarter of the year; (2) older horses than in yearlings; (3) females than in males and geldings; (4) thoroughbreed and cold-blooded horses than in Swedish standardbreeds and ponies. The level of infection was unaffected by the usage of anthelminthics against nematodes. Of the horses examined 51% had 1-100 worms whereas 14% were infected with more than 100 worms. Of the tapeworm positive horses 72% had mixed infections with both adult and juvenile worms, 20% solely juveniles, and 8% solely adults. The severity of intestinal lesions exacerbated by increasing numbers of A. perfoliata. About 11% of the intestines examined had severe lesions, but there was no history of acute abdominal distress in any of the horses included in this study. Although the number of detectable eggs was significantly higher for horses heavily infected with A. perfoliata, the egg recovery among infected horses was only 35%. An additional field survey comprising 218 horses on 88 premises in central and southern parts of Sweden showed that the prevalence of A. perfoliata egg positive horses was the same as found on faecal examination during the abattoir survey.     

Fine needle aspiration cytology of primary pulmonary meningioma associated with minute meningotheliallike nodules. Report of a case with histologic,immunohistochemical and ultrastructural studies

BACKGROUND: Pulmonary meningioma is an unusual tumor located in the lung. Minute pulmonary meningotheliallike nodules are also uncommon tumor-like lesions found at the pleuropulmonary level as solitary or multiple nodules. The association of both entities is described in a recent report. CASE: A 58-year-old, male smoker without pathology underwent radiologic study before a surgical procedure. A peripheral nodule was found in the left lower lobe of the lung with benign characteristics. Fine needle aspiration cytology was performed under computed tomography guidance. Cytologic examination showed features of transitional meningioma and other lesions near the tumor. Minute pulmonary meningotheliallike nodules were also present. CONCLUSION: A diagnosis of meningioma should be considered when there is a combination of scanty material, whorls composed of concentrically arranged cells and isolated cells with intranuclear inclusions. The simultaneous presence of meningioma and meningotheliallike nodules corroborates the unifying hypothesis of their common origin and the nature of these rare pulmonary lesions.     

Comparative histopathology of grey-horse-melanoma and human malignant melanoma

Equine melanoma shows striking features particularly with regard to clinical development in grey horses: in contrast to malignant melanoma in humans and in solid coloured horses that are characterized by early onset of metastasis, pigment cell tumours display almost benign clinical features in ageing grey horses. Through evolution, grey horses appear to be in a favourable position in regard to the biological behaviour of melanomas. Yet unknown factors inhibiting or retarding early melanoma metastasis may be responsible for this phenomenon. In this study, immunostaining profiles and histopathologic patterns of equine vs. human melanotic tumours were compared. In addition, the expression of melanoma markers currently used in human melanoma detection and characterization were evaluated for their applicability in equine melanoma diagnosis. Immunohistopathologic investigations revealed that benign grey horse melanomas share common features with human blue nevi and with human malignant desmoplastic melanomas, whereas their resemblance to other types of human cutaneous malignant melanomas is less pronounced. Our data equally underline that S-100, proliferating cell nuclear antigen (PCNA), HMB-45, Ki-67, T-311 and CD44 can serve as reliable markers for horse melanomas. Further investigations aiming at identifying factors retarding metastasis in affected grey horses are needed, as they may contribute to the development of novel treatment strategies for human malignant melanoma.     

Comparative Histopathology of Grey‐Horse‐Melanoma and Human Malignant Melanoma

Equine melanoma shows striking features particularly with regard to clinical development in grey horses: in contrast to malignant melanoma in humans and in solid coloured horses that are characterized by early onset of metastasis, pigment cell tumours display almost benign clinical features in ageing grey horses. Through evolution, grey horses appear to be in a favourable position in regard to the biological behaviour of melanomas. Yet unknown factors inhibiting or retarding early melanoma metastasis may be responsible for this phenomenon. In this study, immunostaining profiles and histopathologic patterns of equine vs. human melanotic tumours were compared. In addition, the expression of melanoma markers currently used in human melanoma detection and characterization were evaluated for their applicability in equine melanoma diagnosis. Immunohistopathologic investigations revealed that benign grey horse melanomas share common features with human blue nevi and with human malignant desmoplastic melanomas, whereas their resemblance to other types of human cutaneous malignant melanomas is less pronounced. Our data equally underline that S‐100, proliferating cell nuclear antigen (PCNA), HMB‐45, Ki‐67, T‐311 and CD44 can serve as reliable markers for horse melanomas. Further investigations aiming at identifying factors retarding metastasis in affected grey horses are needed, as they may contribute to the development of novel treatment strategies for human malignant melanoma.     

Calcium transport and regulation in human primary and metastatic melanoma.

Thioredoxin reductase (TR) activity on primary melanomas and in surrounding skin is regulated by calcium and, therefore, TR activity can be used to measure the flux of calcium between primary tumors and their surrounding epidermis. Calcium uptake in human melanotic melanoma cell lines SKmel-23 (metastatic) and BC-PT-1 (primary) is related to the density of beta-2-adrenoceptors. The non-pigmented cell line HT-144 (metastatic), did not express beta-2-adrenoceptors, yielding a slow rate of calcium uptake compared to SKmel-23 and BC-PT-1. Cell extracts from melanotic and amelanotic melanoma tissues did not contain a phenylethanolamine-N-methyltransferase (PNMT) for the biosynthesis of epinephrine from norepinephrine and S-adenosylmethionine. However, human full-thickness skin, epidermis and cell cultures of human keratinocytes contained significant PNMT activities. Taken together, these results indicate that (a), TR can be used to monitor calcium flux between primary melanomas and their surrounding skin and vice versa and (b), calcium uptake may be regulated by stimulation of beta-2-adrenoceptors on melanotic melanomas by epinephrine synthesized in the surrounding skin.     

Clinicopathological characteristics associated with BRAFK601E and BRAFL597 mutations in melanoma

BRAF mutations at codons L597 and K601 occur uncommonly in melanoma. Clinical and pathological associations of these mutations were investigated in a cohort of 1119 patients with known BRAF mutation status. A BRAF mutation was identified in 435 patients; Mutations at L597 and the K601E mutation were seen in 3.4 and 3.2% of these, respectively. K601E melanomas tended to occur in male patients, a median age of 58 yr, were generally found on the trunk (64%) and uncommonly associated with chronically sun‐damaged (CSD) skin. BRAF L597 melanomas occurred in older patients (median 66 yr), but were associated with CSD skin (extremities or head and neck location – 73.3%, P = 0.001). Twenty‐three percent of patients with V600E‐ and 43% of patients with K601E‐mutant melanomas presented with nodal disease at diagnosis compared to just 14% of patients with BRAF wild‐type tumors (P = 0.001 and 0.006, respectively). Overall, these mutations represent a significant minority of BRAF mutations, but have distinct clinicopathological phenotypes and clinical behaviors.     

Fine needle aspiration biopsy in uveal melanoma

Fine needle aspiration (FNA) biopsies were performed in a series of patients with uveal tumors. Cytopathologic examination established the correct diagnosis in 26 of 29 uveal melanomas. FNA biopsy was able to exclude the diagnosis of a malignant neoplasm in five nonmelanoma tumefactions. Histologic and FNA cytologic typing of melanomas as epithelioid or predominantly spindle cell showed good agreement, with the same classifications made in 14 of 18 cases. FNA biopsy specimens also proved to be adequate for DNA-content and cell-cycling studies. The cessation of cell cycling in successfully irradiated melanomas may be useful in establishing the postradiation status of tumors that have questionable growths after therapy, as was shown using FNA samples in three such cases in this study. The results of this study show that FNA biopsy is a useful diagnostic adjunct in patients with atypical lesions that require therapy.     

巨大浅表性脂肪瘤样痣一例并文献复习

目的:本研究探讨巨大浅表性脂肪瘤样痣(NLCS)的临床表现、病理特征及预后。方法:回顾性分析一例巨大NLCS的临床表现、病理学特征及预后情况,并结合文献进行复习。结果:本例患者皮损分布于腰臀部,呈群集状丘疹和结节。病理学特征为在真皮胶原组织内见成熟无包膜的脂肪组织。经手术切除后,取得了满意的效果。术后八个月,随诊复查未见异常,至今无复发。结论:巨大NLCS的确诊主要依靠组织病理检查,手术是治疗NLCS的首选方法。     

Adrenal Incidentalomas, 2003 to 2005: Experience After Publication of the National Institutes of Health Consensus Statement

ObjectiveTo determine the clinical outcomes and follow-up imaging characteristics for incidentally discovered adrenal nodules at a large metropolitan health care center, as well as compliance with National Institutes of Health guidelines for the evaluation of these lesions.MethodsBetween October 2003 and June 2005, computed tomographic (CT) scanning performed at Harvard Vanguard Medical Associates detected 165 adrenal nodules (incidentalomas) in 129 patients without extra-adrenal malignant lesions or evidence of adrenal hyperfunction. Nodule characteristics, including size at baseline, change in size at follow-up, CT attenuation values, biochemical data, and clinical outcomes, were analyzed.ResultsOf the 165 adrenal incidentalomas, 96% were smaller than 4 cm. When attenuation values were determined, 65% were low (< 10 Housfield units). Ninetyeight patients (76%) with 142 nodules (86% of all incidentalomas) had at least 1 follow-up CT scan. Of these 142 lesions, 20 (14%) changed significantly in size (grew or became smaller by 0.5 cm or more). Growth was detected within 12 months in 5 of the 7 lesions (71%) that grew. For 95% of patients, the adrenal nodule did not necessitate intervention, including change in medication or surgical treatment. Biochemical studies for adrenal hyperfunction were done in 39 of the overall 129 patients (30%), but in only 20 of 109 patients (18%) not seen by endocrinologists.ConclusionMost adrenal incidentalomas are benign, nonfunctional tumors. Growth typically occurs within 12 months after detection. Despite the 2002 National Institutes of Health guidelines, 82% of patients at our medical center with adrenal nodules who were not seen by endocrinologists did not have hormonal testing. More physician education about the evaluation of incidentalomas should be provided, and prospective studies to establish the appropriate duration of follow-up should be conducted. (Endocr Pract. 2008;14:279-284)     

Diagnostic pitfalls in the fine needle aspiration of thyroid nodules. A study of 555 cases in Chinese patients

The diagnostic value and limitations of fine needle aspiration (FNA) were determined by examining 555 palpable thyroid nodules in Chinese patients who had a definitive diagnosis established by thyroidectomy (529 cases) or large-needle biopsy (26 cases). Of the aspirates, 97.8% were satisfactory for cytologic examination. The overall malignancy rate was 20%. FNA detected 73 (74.5%) of 98 primary malignant tumors and 9 (90%) of 10 metastatic tumors. Diagnostic errors were most commonly due to inadequate specimens and cystic lesions. Cystic fluid, present in one-third of all lesions, was associated with a malignant nodule in 13% of the cases. FNA was most valuable for detecting papillary carcinomas; it may at times suggest the likelihood of a follicular carcinoma.     

Comparison of nuclear DNA content in primary and metastatic malignant melanoma.

The DNA patterns obtained from 23 primary malignant melanomas and 35 corresponding metastases were compared and found to differ in many cases. In eight cases the primary tumors and their metastases had a ploidy type I ("euploid") DNA pattern. One case had a type I primary tumor and both type I and type II metastases. Five cases had type I primary tumors and ploidy type II ("aneuploid") DNA pattern metastases. In five cases the primary tumors and corresponding metastases were type II, and in another four cases the primary tumors were type II, whereas the metastases were type I. We interpret these data as indicating that malignant melanomas (more often than adenocarcinomas) are composed of genetically heterogeneous tumor sublines that frequently give rise to heterogeneously composed metastases. Since we sometimes observed a change in the DNA content in malignant melanomas, it seems to be more difficult to obtain prognostic information from DNA analysis in malignant melanoma as compared to the more stable adenocarcinomas.     

Monoclonal Antibody MAT-1 Against Human Tyrosinase Can Detect Melanogenic Cells on Formalin-Fixed Paraffin-Embedded Sections

Immunohistochemical localization of tyrosinase was examined with a monoclonal antibody (MoAb MAT-1) against human tyrosinase on routine formalin-fixed paraffin-embedded sections of 3 normal skin specimens, 15 melanocytic tumors (6 pigmented nevi, 3 juvenile melanomas and 6 malignant melanomas) and 3 non-melanocytic tumors. In the melanotic melanomas, almost all tumor cells were clearly stained with the antibody. In the nevocytic nevi, the nevus cells in lower epidermis and upper dermis were positive for MoAb MAT-1, but negative in middle and lower dermis. All three juvenile melanomas, one amelanotic melanoma, and three non-melanocytic tumors were entirely negative for MoAb MAT-1. Thus, MoAb MAT-1 could recognize the cells with melanogenic activity on routine formalin-fixed paraffin-embedded sections. However, the staining quality was not adequate for normal epidermal melanocytes, indicating that small technical innovations in the immunostaining process such as formalin fixation after PBS washing are required. Nevertheless, MoAb MAT-1 can be expected to be very useful for identifying melanogenic cells on paraffin-embedded sections, because we have to date no other antibody available for it.     

Collagenase-3 (MMP-13) expression in cutaneous malignant melanoma

BACKGROUND: Matrix metalloproteases (MMPs), enzymes with the ability to degrade the extracellular matrix, play an important role in tissue invasion by cutaneous malignant melanoma (CMM). One specific MMP, collagenase-3 (MMP-13), is thought to have a key function in the activation of MMP. AIMS: To evaluate the expression of MMP-13 in CMM and assess its possible relationship to clinical and pathological parameters. METHODS: MMP-13 expression was analyzed in 51 paraffin-embedded tumor samples from patients with invasive CMM, ten samples from in situ melanomas, and in eight samples from benign lesions (three dermal melanocytic nevi, three compound melanocytic nevi and two atypical melanocytic nevi) using immunohistochemical techniques. The median follow-up period in patients with invasive CMM was 50 months. RESULTS: Benign lesions were consistently negative for MMP-13, whereas three of the ten in situ melanomas (30%) and 23 of the 51 invasive CMMs (45%) showed positive immunostaining for MMP-13. The percentage of MMP-13-positive tumors correlated significantly and positively with the mitotic index (p=0.002) in invasive CMM. However, our results did not show any significant association between tumoral MMP-13 expression and relapse-free survival in patients with invasive CMM. CONCLUSIONS: MMP-13 appears to be a factor associated with tumor aggressiveness in CMM. It seems to eliminate an important barrier not only against tumoral invasion but also against proliferation.     

Problems in assessing multiple cutaneous melanoma. A review on the accuracy of a population based cancer registry

Databases with information on malignant tumors are of great value for epidemiologic studies. From the Regional South Swedish Tumour Registry, which is of documented high quality, 24 patients out of 8008 with reported melanoma diagnosis 1973–2003 were reported as having multiple (≥3) primary, invasive cutaneous malignant melanomas (CMM). Of the 76 tumours identified in these patients, 7 (9%) were found not to be invasive melanomas. Additional cases could be put into question since the lesions could be interpreted as epidermotropic metastases, a diagnosis which can be difficult to establish reliably by microscopic examination. Among the 24 patients we could also identify 8 (10%) additional lesions representing invasive CMM, not included in the Tumour Registry database. Thorough information concerning an earlier melanoma diagnosis and its site of presentation is needed from the clinician and the pathologist for optimal assessment of the histology and the prognostication of the patient, as well as proper reporting to a tumour registry. Identifying multiple primary malignant melanomas is also of special importance for counselling patients belonging to families with hereditary disease. In this study it is shown that diagnosing and reporting multiple malignant melanomas can be problematic due to insufficient communication and to the rare and deceptive capability of cutaneous metastases to imitate primary tumours.