Histogenetic Type Research Articles

Сочетание синдрома Миллера Фишера и неспецифицированной периферической Т-клеточной лимфомы

The article presents a clinical case of combination of Miller Fisher syndrome and unspecified peripheral T-cell lymphoma, which is an aggressive disease with an extremely poor prognosis. The pathogenetic treatment of the identified syndrome did not cause an improvement in the patient's condition and did not affect the expected unfavorable prognosis of the primary malignant disease, for which chemotherapy was not carried out due to the extremely serious condition of the patient. This case emphasizes the importance of an oncological search in patients with Miller Fisher syndrome and the mandatory determination of onconeural antibodies used in the diagnosis of paraneoplastic neurological syndrome, which occurs in malignant tumors of various histogenetic types. Keywords: unspecified peripheral T-cell lymphoma, paraneoplastic neurological syndrome, Guillain-Barré syndrome, Miller Fisher syndrome.

Development features of pericarp of Couroupita guianensis Aubl. (Lecythidaceae)

At present, there is a paucity of works dedicated to carpological investigations of Couroupita guianensis Aubl. In order to identify structural features, particularly those related to fruit histogenesis and determination of its histogenetic type, we examined the anatomical and morphological characteristics of the fruit of C. guianensis at different stages of development. The observed structure of the pericarp allows for the identification of a specialized morphogenetic type of amphicarp, which has not been previously reported in other representatives of Magnoliophyta. The sclerenchymatous zones are localized in the outer and middle zones of the mesocarp. The morphological and anatomical features of the fruit indicate a discrepancy between the structure of the pericarp and the contemporary method of C. guianensis dissemination. It is hypothesized that the fruit is endozoochorous, although among the present-day fauna of South America, there are no animals capable of breaking the integrity of the powerful bony structure of the fruit, which is represented by the internal sclerenchymatous zone. Apparently, C. guianensis lost its potential disseminators after the late Quaternary extinction of megafauna. As hypothetical disseminators, some representatives of the families Megatheriidae, Nothrotheriidae, Gomphotheriidae, Mammutidae, and Toxodontidae could be suggested. Based on our investigations, we can conclude that the fruit of C. guianensis currently illustrates an evolutionary anachronism of dissemination.

Impact of Amplified Oncogenes on Salivary Gland Carcinomas.

In normal epithelia, proto-oncogenes regulate critical intra- or intercellular functions, including cell growth and proliferation, apoptosis, and signaling transduction from the cell periphery (extracellular space) to the nucleus mediated by different pathways. Oncogenes are the mutated or amplified forms of the corresponding proto-oncogenes that are crucially involved in cell neoplastic and malignant transformation during carcinogenesis. Salivary gland carcinomas (SGCs) demonstrate a variety of histogenetic types. They are characterized by a broad spectrum of chromosomal and gene alterations. In particular, amplifications in specific genes [human epidermal growth factor receptor 2 (HER2), human epidermal growth factor receptor 4 (HER4), epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), Mouse double minute 2 homolog (MDM2), androgen receptor (AR), programmed death (ligand 1 (PD-L1), neurogenic differentiation factor 2 (NEUROD2), phosphatidylinositol 3,4,5-trisphosphate-dependent RAC exchanger 1 protein (PREX1), cyclin-dependent kinase4/6 (CDK4/6), proline-rich acidic protein 1 (PRAP1), kell antigen system (KEL), glutamate receptor subunit epsilon 2 (GRIN2D), Ewing sarcoma RNA-binding protein 1 (EWSR1), MYC proto-oncogene (MYC)] combined or not with chromosomal numerical imbalances (aneuploidy/ polysomy/monosomy) form different genetic signatures affecting the response to monoclonal antibody-based, oncologicaly targeted regimens. Different SGC histotypes demonstrate specific combinations of mutated/amplified genes that modify their clinicohistological features. In the current molecular review, we present the most important amplified oncogenes and their impact on the biological behavior of SGCS.

Acceptability of Oesogastroduodenal Fibroscopy in Private Health Facilities from the City of Bobo-Dioulasso in Burkina Faso

The oesogastroduodenal fibroscopy (OGDF) remains a reference examination for the exploration and treatment of digestive pathologies, but is subject to apprehension during its practice. This research studied the factors associated with the acceptability of oesogastroduodenal fibroscopy in private health facilities in the city of Bobo-Dioulasso, in Burkina Faso. This were a cross-sectional study with prospective collection from 1 June to 10 December 2021 with data inclusion from 1 January 2013 to 31 December 2020. The data collected concerned notified cases of tumours and those diagnosed with cancer, socio-demographic characteristics, location and histological and histogenetic types of these cancers. From a sample of 180 patients, the mean age was 43 ± 15.1 years-old with a sex ratio of 1.1. The mean score of acceptability of oesogastroduodenal fibroscopy was low with 53.3% of patients having an acceptability score ≤ 107. As well, the mean score of information received by patients about OGDF was low. At univariate analysis, the factors associated with the acceptability of FOGD were: the presence of discomfort (p=0.041), the presence of anxiety (p=0.040), and the desire to forego performing the examination (p=0.007). In multivariate analysis, we did not find any factors associated with the acceptability of esogastroduodenal fibroscopy. The acceptability of esogastroduodenal fibroscopy is very important in the context of quality improvement in health care. The continuous training of health care personnel on oesogastroduodenal fibroscopy, as well as better patient education on FOGD during a pre-OGDF consultation, is an asset to achieve its acceptability by patients.

Public Health Implications of Types of Cancers in Anatomy-Pathology at the Souro Sanou University Center in Bobo-Dioulasso, Burkina Faso

Cancers are the second largest epidemiological burden in Africa. This led us to study the hospital proportions and histological and histogenetic types of cancers in anatomical pathology at the Souro Sanou University Hospital (CHUSS) in Bobo-Dioulasso, and the possible implications for public health. This was a cross-sectional study that ran from June 1 to December 10, 2021 with data inclusion from January 1, 2013 to December 31, 2020. The data collected concerned: notified cases of tumors and those diagnosed with cancer, sociodemographic characteristics, location and histological and histogenetic types of these cancers. Of the 6,316 cancer cases notified by the different clinical services from 2013 to 2020, there were 1,388 cases of cancer confirmed (or 22.0%) by histology at the CHUSS anatomy-pathology department. Of the 3,605 specimens analyzed, this represented a malignancy proportion of 38.5%. There was an average annual number of 173.5 confirmed cancer cases per year. For a sex ratio of 0.4 and a female predominance of 72.1%, the average age of the cancer cases was 49.3±3.9 years (extremes from 1 to 92 years), with the 40–60-year age group being the most represented (46.4%) and those under 15 years of age representing 3.2%. The organs most affected by cancer were breast (25.5%), uterus (22.4%) and stomach (9.1%). Breast (32.9%) and cervical (31.1%) cancers were the most common in women. In men, the most frequent cancers were: stomach (19.8%) and prostate (13.9%). Histologically, more than two out of five cancers were carcinomas. Squamous cell carcinomas accounted for 43.37%, and adenocarcinomas were found in 13.61%. There was no difference in histogenetic or histological type according to age or sex. Affecting more the less than 60 years with 75,1%, it is about cancers avoidable by actions of promotion and prevention in public health. This underlines the importance of setting up a cancer registry and organizing cancer care based on promotion and primary prevention.

Morpho-Anatomy of the Gynoecium and Fruit in Three Ornamental Members of Campanuloideae (Campanulaceae)

Abstract Gynoecium and fruit micromorphology and anatomy were studied using light microscopy in three species of Campanuloideae belonging to the tribes Cyanantheae ( Platycodon grandiflorus ), Wahlenbergieae ( Jasione montana ), and Campanuleae ( Adenophora liliifolia ) of the native and cultivated flora of Ukraine, to elucidate structural adaptations for fruit dehiscence. The studied species differed in flower/fruit orientation, carpel number, ovary insertion, and capsule-opening position, and the information provided a background for the discovery of common anatomical features influencing fruit dehiscence. In the studied species, the synascidiate and symplicate zones in the ovary and prominent placentae were found to be located near the mid-region of the ovary. The distinct innervation of the ovary wall and ovules was described. In P. grandiflorus , the septa and fruit wall contained a lignified parenchyma in a subepidermal position, while in J. montana and A. liliifolia , lignification was observed only in proximal portions of the septa, above the placenta ( J. montana ), or was noted as a narrow strand from the ovary base to the mid-region, called “axicorn” ( A. liliifolia ). In all the studied species, unlignified endocarpium was detected. The semi-inferior capsule of P. grandiflorus has been defined as a capsule of the Forsythia -type, with a sclerenchymatous layer in the inner zone of the mesocarpium. In J. montana and A. liliifolia , a new histogenetic type of capsule is described as Campanula -type, without lignified layers in the fruit wall and with lignified tissue in the septa, which enabled dehiscence. Our study proposed for the first time the classification of the capsules found in the studied species based on the development of openings in the superior or inferior regions of the fruits. The upright fruits of P. grandiflorus and J. montana reveal incomplete dorsiventral dehiscence in the superior region of the fruit, while dehiscence of pendent fruits of A. liliifolia is hippocrepiform-septifragal interlocular and occurs in the inferior region of the fruit at its base, as revealed previously in Campanula latifolia fruit.

Prognostic risk factors of first recurrence in patients with primary stages I–II cutaneous malignant melanoma – from the population‐based Swedish melanoma register

Prognostic factors in patients with localized primary cutaneous malignant melanoma (CMM) are well described. However, prognostic factors for recurrence are less documented. The aim of this study was to identify prognostic risk factors for first recurrence in patients with localized stages I-II CMM using population-based data. This study included 1437 CMM patients registered in one region of Sweden during 1999-2012 follow-up through 31 December 2012. To identify first recurrence of CMM disease, data from a care data warehouse, the pathology and radiology department registries were used. Patients were also followed through a census register and the national Cause of Death Register. The 5- and 10-year recurrence-free survival (RFS) were 85.7% and 81.2%, respectively. The most common site of first recurrence was regional lymph node metastasis closely followed by distant metastasis. After adjusting for all prognostic factors, women had 50% lower risk of recurrence than men (HR = 0.5, 95% CI 0.4-0.7) and patients ≥70 had higher risk compared to patients 55-69 years (HR = 1.7, 95% CI 1.2-2.5). Other significant prognostic factors for risk of recurrence were tumour thickness, presence of ulceration, Clark's level of invasion and histogenetic type. Tumour thickness was found to be the predominant risk factor for recurrence. The prognostic factors for recurrence coincided with prognostic factors for CMM death. The most common site of first recurrence in stages I-II CMM is regional lymph node (42.8%) closely followed by distant metastases (37.6%), a fact which has to be taken into consideration when choosing follow-up strategies.

Newly Available Antibodies With Practical Applications in Surgical Pathology

Selected antibodies that have become available in recent years and have applications in diagnostic pathology are discussed. They include antibodies that are organ-related, provide information on cellular differentiation or histogenetic type, have predictive value in tumors, and highlight infective agents. PAX8 (paired box gene 8) is a marker expressed in the lower female genital tract, thyroid, and kidney and their tumors. Napsin A is expressed in the lung and kidney and is an alternative marker for pulmonary adenocarcinoma. Arginase A is a sensitive and specific marker for liver tumors. ERG (Ets-related gene) is an excellent marker for endothelium and vascular tumors as well as prostatic cancer (about 50% of cases). SOX10 (SRY-related HMG box) is expressed predominantly in melanocytic and Schwann cells and the corresponding tumors. DOG1 (discovered on GIST 1) is an excellent marker for gastrointestinal stromal tumor (GIST) and acinic cell carcinoma. OCT3/4 is a pan-germ cell tumor marker, except yolk sac tumor. SALL4 is positive in various types of germ cell tumors, including yolk sac tumor. MUC4 (mucin-related antigen 4) is a sensitive and specific marker for low-grade fibromyxoid sarcoma. Langerin is a specific marker for Langerhans cells and their tumors. SOX11 is a sensitive marker for mantle cell lymphoma. New generation antibodies against anaplastic lymphoma kinase (ALK) are required to reliably demonstrate ALK gene translocation in pulmonary carcinomas. Lack of expression of succinate dehydrogenase B is seen in paragangliomas of the hereditary form and in the pediatric type of GIST. Antibodies against Trepenoma pallidum can facilitate the diagnosis of syphilis, whereas those against SV40 (simian virus 40) are helpful for diagnosis of BK virus infection and progressive multifocal leukoencephalopathy.

The many faces of acinic cell carcinomas of the salivary glands: a study of 40 cases relating histological and immunohistological subtypes to clinical parameters and prognosis

To study the morphological heterogeneity of acinic cell carcinoma (ACC) in correlation with clinicopathological parameters. Forty well-characterized ACCs were classified as solid (n = 20), microcystic (n = 15), papillary-cystic (n = 4) or follicular (n = 1), based on the dominant architectural growth pattern. Fourteen tumours exhibited eosinophilic/clear cell morphology and 18 tumours were rich in zymogen granules (so-called blue dot tumours). High-grade morphology occurred in five tumours. Based on cytokeratin (CK) 7 staining and in analogy to CK7 expression in normal salivary gland epithelia, three distinct histogenetic subtypes were recognized: acinar (CK7-negative; n = 13), ductular (diffuse CK7-positive; n = 11) and mixed ductulo-acinar (10-66% CK7-positive cells; n = 16). Most papillary-cystic tumours displayed ductular differentiation (P = 0.015), whereas blue dot tumours never did (P < 0.001). Analysis of relapse-free survival (RFS) revealed that Stage I tumours had the best prognosis without any relapse in 18 years follow-up (P = 0.06). High-grade tumours were associated with shorter RFS (P = 0.028). Concerning the histogenetic types, monophasic (pure acinar or ductular) tumours were associated with a significantly better RFS than mixed ductulo-acinar tumours (P = 0.008). The results underscore the great histological diversity of ACC, and the value of histogenetic subtyping as an additional prognostic factor regarding RFS.

Retrospective study on the cutaneous head and neck melanoma in Dorset (UK)

Trends in the incidence and the sites of primary malignant melanoma on the skin of head and neck in Dorset as well as the outcome of treated cases were overviewed for the first time. Increase in incidence rate of cutaneous head and neck melanoma from 1.3 per 100,000 in 2004 to 3.1 per 100,000 in 2007 was recorded. The most prevalent histogenetic type of cutaneous malignant melanoma on head and neck in our study was melanoma of superficial spreading type 35.1% ( n = 20) of all registered cases. Superficial spreading melanoma apart from being the most common type of malignant melanoma of the head and neck in Dorset also showed increase in the number of diagnosed cases of the reviewed years. It increased from 2 (22.2%) of all head and neck melanoma cases in 2004 to 7 (30.4%) in 2007. The average age at the time of diagnosis the cutaneous malignant melanoma of head and neck for both men and women was 73.5 years. Breslow thickness, Clark's level of invasion, tumour ulceration and anatomical site remained the most important prognostic factors. Correlation between Breslow thickness and Clark's level of invasion found to be stronger in men.

The Complex Relationships Between Sentinel Node Positivity, Patient Age, and Primary Tumor Desmoplasia: Analysis of 2303 Melanoma Patients Treated at a Single Center

Recent studies have shown that younger age is associated with a greater likelihood of positive sentinel node (SN) status in patients with localized melanoma. This is a paradoxical situation because it is well known that younger patients have a far more favorable overall survival rate than older patients. In addition, desmoplastic melanomas are associated with a lower frequency of SN positivity, although this is less well documented. The outcome for 2303 cutaneous melanoma patients undergoing sentinel lymph node biopsy (SLNB) at the Sydney Melanoma Unit between 1993 and 2006 was examined to clarify the role of patient age and desmoplastic histogenetic type on SN positivity. By univariate analysis, patients aged <40 years had a higher SN positivity rate (22.6%) than patients aged > or =40 years (15.4%; P < .004). Features associated with SN positivity were tumor thickness, mitotic rate, ulcerative state, and nondesmoplastic histogenetic type (all P < .001). Patient sex and primary melanoma site were not statistically significantly associated. Multivariate analyses revealed that only tumor thickness, patient age, nondesmoplastic type (all P < .001), and ulceration (P < .026) were independently associated with SN positivity. Key prognostic determinants such as total number of disease-positive nodes (both SNs and non-SNs) and site of first relapse did not vary according to age. Tumor thickness, patient age, desmoplastic histogenetic type, and primary melanoma ulceration were all independently associated with SN status. The factors underlying the paradox of a poorer survival rate in older patients despite a lower incidence of positive SNs remain unclear.

Cyclooxygenase-2 and Epidermal Growth Factor Receptor Expressions in Different Histological Subtypes of Cervical Carcinomas

This study was designed to evaluate the significance of cyclooxygenase (COX)-2 and epidermal growth factor receptor (EGFR) expression in a series of cervical adenocarcinoma (AC), cervical adenosquamous carcinoma (ASC), and cervical squamous cell carcinoma (SCC). One hundred thirty cases of cervical carcinoma (30 ASC, 50 AC, and 50 SCC) were analyzed for COX-2 and EGFR expressions using specific primary antibodies. Samples were scored semiquantitatively as follows: (-), 0% of immunoreactive cells; (+), <5% of immunoreactive cells; (++), 5% to 50% of immunoreactive cells; and (+++), >50% of immunoreactive cells. The COX-2 expression was more frequently positive than EGFR in all cervical cancers studied. The COX-2 expression was also more prominent in AC than in ASC (P = 0.003). Expression of either COX-2 or EGFR was significantly different when comparing SCC with AC (P < 0.001 and P = 0.04, respectively). There was no significant correlation between COX-2 and EGFR expressions and age at diagnosis, recurrence, distant metastasis, and/or positive status of regional lymph nodes, neither between COX-2 and EGFR coexpression and the clinical data analyzed. Nevertheless, our data support that there are significant differences between EGFR and COX-2 expressions in the 3 different histogenetic types of cervical cancer. Also, in terms of therapeutic strategies, our data can be valuable in the selection of patients eligible to receive specific EGFR/COX-2-targeted therapy.

Clinicopathological analysis of 1571 cutaneous malignant melanomas in Valencia, Spain: factors related to tumour thickness

Epidemiological studies on cutaneous melanoma in Mediterranean countries are scarce. Our aim was to perform a descriptive analysis of melanoma cases diagnosed in Valencia, Spain, and to evaluate the relationship between Breslow thickness and some clinical features. A total of 1571 patients with histologically confirmed cutaneous malignant melanoma diagnosed at the two main referral melanoma centres were evaluated retrospectively. For each patient the following clinical and pathological characteristics were selected: age, gender, anatomic site, histogenetic type, Breslow thickness, presence of ulceration, the stage, and symptoms such as bleeding, changes in size and colour, altered sensations and previous traumas. Chi-squared tests were performed together with logistic regression to evaluate the relationship of variables with tumour thickness. Tumour thickness was independently correlated with increasing age, presence of bleeding, location on hand or foot, and presence of altered sensations. Female sex and presence of a change in colour were associated with thin melanomas. Ideally, public awareness campaigns concerning the risks that exist should be aimed at subgroups such as men and people of an advanced age who generally present with thicker tumours. Emphasis should be placed on irregularities or changes in pigmentation, as these appear to be the first indicators of the development of a melanoma.

Follicular dendritic cell tumor of the gastrointestinal tract: Report of a rare neoplasm and literature review

Follicular dendritic cell (FDC) tumor is a rare neoplasm of the accessory immune system showing FDC differentiation. Histologically, a conventional type and an inflammatory pseudotumor (IPT-like) type are recognized. The etiology of FDC tumor is unknown. While rare FDC tumors were associated with hyaline-vascular Castleman's disease (HVCD), hepatosplenic IPT-like FDC tumors consistently harbor EBV infection. FDC tumors of the gastrointestinal (GI) tract and mesentery/omentum are exceedingly rare, with only 17 cases reported so far. We report an additional case of an IPT-like FDC tumor of the ileum and mesentery in a 52-year-old schizophrenic man. The tumor consisted of highly atypical multinucleated giant cells in a background of intense lymphoid infiltrate with prominent eosinophilia reminiscent of Hodgkin's lymphoma. Tumor cells were immunoreactive for vimentin, CD21, CD35, fascin, smooth muscle actin and CD68, but were negative for all lineage-specific lymphoreticular, myeloid, mesenchymal and epithelial markers. Immunostaining for HHV-8 and in situ hybridization for EBV-encoded RNA (EBER) were negative. Some mesenteric lymph nodes showed HVCD-like changes. The differential diagnostic considerations of this unusual and rare neoplasm, mainly lymphocyte-rich GI stromal tumor (GIST), malignant lymphoma and inflammatory neoplasia of diverse histogenetic types, will be discussed together with a literature review on gastrointestinal FDC tumors.

Increasing Incidence of Lentigo Maligna Melanoma Subtypes: Northern California and National Trends 1990–2000

Worldwide, lentigo maligna melanoma (LMM) comprises 4%-15% of cutaneous melanoma and occurs less commonly than superficial spreading or nodular subtypes. We assessed the incidence of melanoma subtypes in regional and national Surveillance, Epidemiology, and End Results (SEER) cancer registry data from 1990 to 2000. Because 30%-50% of SEER data were not classified by histogenetic type, we compared the observed SEER trends with an age-matched population of 1024 cases from Stanford University Medical Center (SUMC) (1995-2000). SEER data revealed lentigo maligna (LM) as the most prevalent in situ subtype (79%-83%), and that LMM has been increasing at a higher rate compared with other subtypes and to all invasive melanoma combined for patients aged 45-64 and > or =65 y. The SUMC data demonstrated LM and LMM as the only subtypes increasing in incidence over the study period. In both groups, LM comprised > or =75% of in situ melanoma and LMM > or =27% of invasive melanoma in men 65 y and older. Regional and national SEER data suggest an increasing incidence of LM and LMM, particularly in men > or =age 65. An increased incidence of LM subtypes should direct melanoma screening to heavily sun-exposed sites, where these subtypes predominate.

Invasive cutaneous malignant melanoma in Sweden, 1990-1999. A prospective, population-based study of survival and prognostic factors.

The objective of the current study was to compile prospective, population-based data on cutaneous invasive melanomas in Sweden during the period from 1990 to 1999, to describe and analyze survival data and prognostic factors, and to make comparisons with previously published Swedish and international data. Twelve thousand five hundred thirty-three patients, which included 97% of all registered melanomas in Sweden, were included and described. Among these, 9515 patients with clinical Stage I and II melanoma were included in an analysis of survival and in a univariate analysis, and 6191 patients were included in a multivariate analysis of prognostic factors. There was no significant change in melanoma incidence during 1990-1999. Favorable prognostic factors were found, especially in younger and female patients, resulting in a relative 5-year survival rate of 91.5%. In the multivariate analysis, significant factors that had a negative effect on survival were Clark level of invasion, Breslow thickness, ulceration, older patient age, trunk location, greatest tumor dimension, nodular histogenetic type, and male gender. During the period from 1990 to 1999, the 5-year survival of patients with malignant melanoma in Sweden was better compared with the previously reported rates in published, population-based studies from Sweden, probably as a result of better secondary prevention due to better knowledge and awareness by both patients and the medical profession. The more favorable prognostic factors and the change in melanoma location found in younger patients, compared with earlier reports, may reflect changes in clothing as well as tanning habits; however, a decrease also was found in Clark Level II and thin melanomas for the same patient group. The authors concluded that further improvements can be achieved with better access to health care and with the use of early melanoma detection campaigns.

The incidence of cutaneous melanoma on Crete, Greece

For Greece, no data regarding the incidence of cutaneous melanoma (CM) have been reported. In this report, we present epidemiologic data for CM on Crete, an island in southern Greece, during the years 1999-2002. We attempt a comparison with corresponding data reported for the Italian population. One hundred and two CM patients of Cretan origin with primary CM first diagnosed between the years 1999-2002 were interviewed and underwent complete skin examination by the same two experienced dermatologists. Crude and/or age-standardized incidence rates were calculated for Crete as a whole, as well as for each one of the four prefectures of the island. The age-standardized incidence rate according to the Greek population was 4.6 per 100,000 person-years for men and 4.7 per 100,000 person-years for women. The crude incidence rates did not differ significantly between the four prefectures. Significant differences between Cretan and Italian CM patients were found in terms of gender, age at diagnosis, anatomic site and histogenetic type of CM, hair color, skin reaction to sun exposure, history of sunburn before the age of 15 years, presence of solar lentigines, and total common nevus count. The incidence of CM on Crete is higher than that estimated for the whole of Greece and comparable with the incidence reported for other southern European countries.

Classifying Melanocytic Tumors Based on DNA Copy Number Changes

Melanoma and benign melanocytic nevi can overlap significantly in their histopathological presentation and misdiagnoses are common. To determine whether genetic criteria can be of diagnostic help we determined DNA copy number changes in 186 melanocytic tumors (132 melanomas and 54 benign nevi) using comparative genomic hybridization. We found highly significant differences between melanomas and nevi. Whereas 127 (96.2%) of the melanomas had some form of chromosomal aberration, only 7 (13.0%) of the benign nevi cases had aberrations. All seven cases with aberrations were Spitz nevi, in six of which the aberration was an isolated gain involving the entire short arm of chromosome 11. This aberration was not observed in any of the 132 melanomas. We also analyzed the 132 melanomas for genetic differences depending on anatomical site, Clark's histogenetic type, and sun-exposure pattern. We show that melanomas on acral sites have significantly more aberrations involving chromosomes 5p, 11q, 12q, and 15, as well as focused gene amplifications. Melanomas classified as lentigo maligna melanomas or as occurring on severely sun-damaged skin showed markedly more frequent losses of chromosomes 17p and 13q. This study shows a pattern of chromosomal aberration in melanoma that is distinct from melanocytic nevi and should be further evaluated as a diagnostic test for melanocytic lesions that are now ambiguous. In addition, we show marked differences in the genetic make-up of melanomas that depend on anatomical location and sun-exposure pattern indicating that potential therapeutic targets might vary among melanoma types.

Incidence trends and familial risks in invasive and in situ cutaneous melanoma by sun-exposed body sites.

We studied incidence trends, age-incidence relationships and familial risks in invasive and in situ cutaneous melanoma, based on the Swedish Family-Cancer Database of more than 10 million individuals. Offspring were 0-66 years of age. Cancers were obtained from the Swedish Cancer Registry from years 1961-98. The study was based on 9,771 offspring and 22,888 parents with invasive melanoma and 2,446 offspring and 5,017 parents with in situ melanoma. Incidence rates increased markedly for invasive melanoma in the trunk. For in situ melanoma, trunk and head and neck were affected, and, in addition, legs for women. The maximal incidence was around age 80 years, independent of the type or site in men; in women early onset superficially spreading melanoma shifted the age for maximal incidence to about 60 years. For in situ melanoma, lentigo maligna was the main histogenetic type in the head and neck but in the trunk and legs superficially spreading melanoma was somewhat more common. Standardized incidence ratios (SIR) were calculated for familial risk at exposed and covered sites. The combined familial risks for invasive and in situ melanoma were higher at covered (SIR 3.56 from parents) than sun-exposed (1.92 from parents) sites and they agreed when familiality was defined between parents and offspring or between siblings; the sibling SIRs were 3.90 at covered and 2.53 at exposed sites. The data suggest that the higher melanoma density at exposed sites masks familial effects. Furthermore, sun exposure does not appear to reinforce the familial effect.

Prognostic factors in patients with thick cutaneous melanoma (&gt; 4 mm)

The current study was conducted to examine the role of multiple clinical and histologic factors in the prognostic assessment of patients with thick primary melanoma (> 4 mm, classified as T4). A retrospective analysis was performed in 329 patients with T4 cutaneous melanomas who were seen at the University of California at San Francisco Melanoma Center between 1978 and 2000. Fourteen histopathologic features were recorded prospectively by a single dermatopathologist. In addition, 9 clinical factors were analyzed. Several histologic factors were found to have a significant impact on the survival of patients with T4 melanoma. On univariate analysis, tumor thickness, ulceration, mitotic rate, microsatellites, vascular involvement, and histogenetic type of the primary tumor all were found to have a significant impact on the overall survival rate. Regional lymph node involvement reduced the overall survival of T4 patients dramatically. The 5-year overall survival of patients with lymph node-negative T4 disease was 61%, compared with 30% for those with lymph node-positive disease. When lymph node status was taken into account, tumor thickness, vascular involvement, and ulceration all remained independent predictors of overall survival on multivariate Cox regression analysis. Neither age, gender, nor anatomic location appeared to affect the recurrence-free or overall survival rates. Patients with thick primary cutaneous melanomas (> 4 mm) comprise a heterogeneous group. The presence or absence of lymph node involvement, vascular involvement, and ulceration appears to result in significantly divergent overall survival rates in this patient cohort. Consideration of these factors has important implications in the management of patients with T4 melanoma.