Familial non-medullary thyroid carcinoma: pathology review in 27 affected cases from 13 French families

BACKGROUND AND OBJECTIVES: When familial non-medullary thyroid cancer (FNMTC) develops with no obvious associated pathogenetic factor, an inherited predisposition may underlie the process. The present study was conducted because detailed pathological findings are lacking in most series of FNMTC. PATIENTS AND METHODS: Thirteen families comprising 27 cases of FNMTC were included (1.8% of differentiated thyroid carcinoma). The family relationship (20 F, 7 M; age 46 +/- 16 years; mean +/- SD) was 'siblings' in eight families, 'parent and child' in four and 'aunt and niece' in one. Careful pathological review of the thyroid tumours (papillary/follicular: 25/2, size: 16 +/- 11 mm) was performed. RESULTS: Initial staging according to extension was as follows: grade I (n = 16), II (n = 2), III (n = 6), IV (n = 3). Fourteen tumours were papillary microcarcinomas (size: 8 +/- 2 mm). No tumour phenotype that may be considered specific for FNMTC was found when considering either age, pathological findings or tumour aggressiveness. Although rare events were found in both relatives of some families suggesting a putative 'familial' phenotype of FNMTC, this may be fortuitous. CONCLUSION: Micro familial non-medullary thyroid cancers are more common than previously reported and further studies are required to be able to distinguish this subgroup from sporadic papillary microcarcinomas. The careful pathological review of the familial non-medullary thyroid cancer in this study does not seem to point to a distinct subgroup of familial differentiated thyroid carcinoma although the data are intriguing. Genetic studies are now required to investigate this issue.     

Acute myeloid leukemia with T-lymphoid features: a distinct biologic and clinical entity

We studied the clinical and biologic features of 10 cases of acute leukemia that met standard French-American-British (FAB) criteria for acute myeloid leukemia (AML) but in which the blast cells also expressed the T-cell-associated CD2 surface antigen. All cases had greater than 3% myeloperoxidase and Sudan black B-positive leukemic blasts, and blasts from seven cases contained Auer rods. Reactivity of the cells with a panel of monoclonal antibodies (MAbs) indicated that leukemic cells in all cases expressed myeloid-associated (CD11b, CD13) surface antigens, further supporting the diagnosis of AML. However, blasts from every patient coexpressed the T-cell-associated surface CD2 and CD7 as well as cytoplasmic CD3 antigens. Blasts from five patients expressed surface CD25, whereas blasts from only one expressed surface CD3. Five patients had rearranged T-cell receptor beta-chain genes, whereas only three had rearranged T-cell receptor gamma-chain genes. This pattern of lineage-related gene expression appears to define a distinct subtype of AML with T-lymphoid features (CD2+ AML) and could reflect either aberrant gene expression in leukemic blasts or transformation of a pluripotent stem cell having a flexible pattern of gene expression. Clinically, these 10 patients presented at an older age with a higher leukocyte count and a higher frequency of lymphadenopathy than did children whose blast cells were characteristic of myeloid leukemia. Patients with CD2+ AML also had poorer responses to remission induction therapy (50% v 80% entered complete remission, P = .05). However, each of the five children who failed induction chemotherapy on AML protocols had a striking response to drug combinations usually reserved for lymphoid leukemia. We conclude that this leukemia with mixed lymphoid and myeloid characteristics is a distinct biologic and clinical entity.     

Mucinous carcinoma of the rectum: a distinct clinicopathological entity

Purpose

The definition of mucinous tumours relies on quantification of the amount of mucus produced by neoplastic cells within the rectum. This has changed over the years to include varying degrees of mucin production. The inconsistency of diagnosis has led to conflicting reports in the literature regarding clinical outcomes and treatment response. A universally accepted definition and improved imaging and surgical techniques in the last decade are now challenging the traditional view of these tumours. The aim of this review was to present the current evidence on the clinicopathological characteristics of mucinous tumours of the rectum.

Methods

A systematic review was conducted using Preferred Reporting for Systematic Reviews and Meta-Analyses guidelines. A literature search was performed using the Ovid SP to search both EMBASE and MEDLINE databases, Google Scholar and PubMed to find all studies relating to mucinous carcinoma of the rectum. The search dates were between 1 January 1965 and 1 March 2013.

Results

Mucinous tumours comprise 5–20 % of all rectal cancers and commonly present at a more advanced stage and in younger patients. They are readily identified on MRI, and the diagnosis is confirmed on histological analysis, demonstrating more than 50 % of extracellular mucin within the tumour complex. They carry an overall worse prognosis compared to adenocarcinoma of the same stage. The response to oncological treatment remains controversial.

Conclusion

Mucinous tumours of the rectum are less well understood than non-mucinous adenocarcinoma. This is due to the inconsistent histopathological definitions of the past making comparison of clinical outcome data difficult. They remain challenging to treat and are associated with a poor prognosis. A universally accepted definition and the role of imaging techniques such as MRI to accurately detect mucinous tumours are likely to lead to a better understanding of these cancers.     

Eosinophilic fasciitis: a distinct clinical entity?

Eosinophilic Fasciitis is a syndrome characterized by exertion related scleroderma-like skin changes, peripheral eosinophilia, hypergammaglobulinemia and diffuse faciitis. Controversy exists as to the precise classification of the syndrome, i.e., whether it is a distinct entity or a variant of scleroderma. We describe a patient with eosinophilic faciitis but with several unique features: 1) progressive skin changes unresponsive to corticosteroid therapy; 2) elevated anti-DNA antibodies; 3) hypocomplementemia; and 4) a followup biopsy showing sclerodermatoid skin changes. These features and others relating to the controversial aspects of classification of eosinophilic fasciitis are discussed.     

True idiopathic splenomegaly - a distinct clinical entity

10 asymptomatic young male patients with moderate splenomegaly detected at a routine examination are presented. The history and clinical examination failed to reveal the aetiology of the splenomegaly. Further investigations, including screening for blood dyscrasias, clotting abnormalities and reticuloendothelial abnormalities were likewise unrevealing. Liver biopsies, rectal biopsies for bilharzia and bone marrow aspirates for Gaucher's Disease were found to be normal. Serology for malaria and Ebstein Barr Virus infection was also negative. Positive immunofluorescent tests for IgG antibodies specific for cytomegalovirus were found in 5 patients. We consider that these patients have splenomegaly which is not of a specific nature, but may be associated with a severe antigeneic response to the previous cytomegalovirus infection. In view of the otherwise negative findings these patients should be considered to have ‘True Idiopathic Splenomegaly’, a term which would indicate the benign nature of the splenic enlargement. This diagnosis should be considered in the differential diagnosis of asymptomatic patients who have splenomegaly of undetermined origin.     

Familial papillary thyroid carcinoma is genetically distinct from familial adenomatous polyposis coli.

Familial papillary thyroid carcinoma (fPTC) is an inherited tumor syndrome characterized by isolated papillary thyroid carcinoma (PTC) in affected subjects. Its etiology is unknown. Large multigeneration families with PTC are very rare, and therefore, modern genetic linkage studies have not been applied extensively to this disorder. Familial adenomatous polyposis coli (FAP) is an inherited tumor syndrome enriched in PTC. FAP is caused by germline mutations of the adenomatous polyposis coli (APC) gene that is located in the 5q21 region. It is not known if fPTC is a phenotypic variant of FAP, or if it is a genetically distinct disorder. We report a large 3-generation fPTC kindred and use linkage analysis to test the hypothesis that fPTC and FAP are genetically distinct. In this kindred there are 25 living informative subjects; 5 have PTC, and 1 is an obligate carrier. Inheritance is autosomal dominant with incomplete penetrance. There is vertical transmission, multifocal disease, an average age of onset of 36 years, and 1 subject has colon cancer. The probability is approximately 1 in 2 billion against the clustering of 5 sporadic PTC cases in this kindred. To test for linkage to the APC gene we used 2 highly polymorphic markers, D5S656 and D5S421, which are located within a maximum distance of 1.7 megabase (Mb) of the APC gene and within an estimated genetic region of less than 1 centimorgan (cM) from each other. After polymerase chain reaction (PCR) amplification 18 family members were genotyped. Construction and inspection of haplotypes showed that the affected subjects do not share the same allelic composition. Using a penetrance ratio of 75%, linkage was excluded at 2 cM and 3 cM on both sides of D5S656 and D5S421, respectively. The combined haplotype of these 2 markers provided an exclusion region of 4 cM. We conclude that fPTC is genetically distinct from FAP.     

Familial papillary carcinoma of the thyroid.

A 38-year-old woman had bilateral papillary thyroid carcinoma. Her brother and mother also had papillary thyroid carcinoma. The literature on familial papillary thyroid carcinoma is reviewed briefly.     

Autoimmune gestational diabetes mellitus: a distinct clinical entity?

This review gives an update of the present knowledge on what is defined here as autoimmune gestational diabetes mellitus (GDM). Autoimmune phenomena associated with type 1 diabetes mellitus (DM) can be detected in a subgroup of women with GDM. Islet autoantibodies are present in sera from women with GDM with variable frequency. Distinct phenotypic and genotypic features may be recognised in this subset of women with GDM, which are representative of a distinct clinical entity. Furthermore, these women are at increased risk of developing type 1 DM after pregnancy. However, the eventual progression of the autoimmune destruction of beta‐cells in these subjects may follow different time‐course patterns thus leading to variable forms of presentation of autoimmune DM. As a high‐risk group for type 1 diabetes, women with previous autoimmune GDM may be candidates for potential immune intervention strategies. Copyright © 2001 John Wiley & Sons, Ltd.     

Does a sliding hiatus hernia constitute a distinct clinical entity?

In a sliding hiatus hernia, the esophagogastric junction is above the diaphragm. It is called a sliding hernia because anatomically it resembles a sliding inguinal hernia and not because of an upward and downward motion through the esophageal hiatus. Symptoms may arise from the hernia because it becomes distended or bleeds; much more commonly the hernia is said to produce gastroesophageal reflux with its secondary complications. However, certain clinical and manometric data suggest that the hernia may be an associated and inconsequential finding so that reflux probably depends upon the lower esophageal sphincter efficiency rather than the presence of a hernia. The role of the phrenoesophageal ligament and its actual existence are still debated. A lower esophageal ring cannot be assumed to indicate that a hernia is present; more than likely the ring marks the upper limits of the lower esophageal sphincter. Although inadequate data are available concerning the natural history of the symptom complex attributed to a hernia, in a large proportion of such patients, symptoms become mild or may disappear on so-called medical therapy. Consequently, the results of surgical therapy need to be cautiously evaluated.     

Pure red cell aplasia of pregnancy: a distinct clinical entity

Summary. We describe a 31-year-old patient with pure red cell aplasia of pregnancy, successfully managed with regular blood transfusions. In vitro studies showed specific inhibition of day 14 erythroid colonies (BFU-E) using serum and purified immunoglobulin G (IgG) obtained from the patient at diagnosis (before blood transfusion). The inhibition of BFU-E disappeared when haematological remission occurred 3 weeks after delivery and she remains clinically well with a normal haemoglobin 4 years later.     

Systemic sclerosis-rheumatoid arthritis overlap syndrome: a unique combination of features suggests a distinct genetic, serological and clinical entity

OBJECTIVE: To determine the genetic, clinical and serological characteristics of systemic sclerosis (SSc)-rheumatoid arthritis (RA) overlap syndrome. METHODS: Clinical manifestations and immunolaboratory features of 22 SSc-RA patients were assessed. The HLA-DR genotype of the 22 SSc-RA patients determined by SSP-PCR was compared with that of 38 SSc patients, 100 RA patients and 50 healthy controls. RESULTS: All overlap patients fulfilled the American College of Rheumatology (ACR) criteria for SSc and RA. Five of the 22 patients (23%) had diffuse cutaneous SSc (dcSSc) and 17 patients (77%) had limited cutaneous SSc (lcSSc). Antinuclear antibody, anti-Scl70, IgM rheumatoid factor and anti-CCP antibody positivity were detected in 22 (100%), 5 (23%), 16 (73%) and 18 patients (82%), respectively. Seventeen patients (77%) had pulmonary fibrosis, 12 (55%) had oesophageal dismotility, 11 (50%) had cardiac and five (23%) had renal involvement. Hand joint destruction was observed in 18 patients (82%). Significantly increased frequencies of HLA-DR3 (36% vs 5%), HLA-DR7 (9% vs 4%), HLA-DR11 (36% vs 7%) and HLA-DRw53 (23% vs 5%) were observed in SSc-RA compared with RA patients (P < 0.05). Allele frequencies of the 'shared epitope' (HLA-DR1 and -DR4) were significantly increased in SSc-RA (32% and 27%, respectively) and RA patients (46% and 31%, respectively) in comparison with SSc patients (10.5% and 16%, respectively) or healthy controls (16% and 14%, respectively) (P < 0.05). CONCLUSIONS: To date this is the largest SSc-RA overlap cohort. Genetics, clinical and immunolaboratory features suggest a mixed phenotype. Our data suggest that SSc-RA overlap syndrome may be a distinct genetic, immunological and clinical entity.     

Is fibromyalgia a distinct clinical entity? The epidemiologist's evidence.

The key features of fibromyalgia are chronic widespread pain, general distress and enhanced pain sensitivity as revealed by a tender point count. Fibromyalgia could be considered a distinct entity if the key features defined a patient group with any one of the following: a characteristics feature or cluster of features with a distribution clearly demarcating the group from the rest of the population, identifiable risk factors, a characteristic natural course or prognosis, or a specific response to treatment. This should be seen in population studies, not only in selected clinic series. The available epidemiological evidence suggests that the distributions of the key features are continuous and no clear population groups can be defined. Also, difficulties in identifying changes such as incidence and recovery, and unreliable measurements of the key features themselves, detract from the utility of the concept of fibromyalgia as an epidemiological entity.