Diane Kenwright

Reproducibility of new classification schemes for the pathology of ductal carcinoma in situ of the breast.

AIM: To compare the interobserver variation in the pathological classification of ductal carcinoma in situ of the breast using two recently proposed classification schemes. METHODS: 11 pathologists classified a set of 25 cases of ductal carcinoma in situ chosen to reflect a range of lesions, using the traditional architectural classification together with the modified cytonuclear grading scheme of Holland et al and the Van Nuys classification scheme. Participating pathologists received a standard tutorial, written information, and illustrative photomicrographs before their assessment of the cases. RESULTS: Interobserver agreement was poorest when using the architectural scheme (kappa = 0.44), largely owing to variations in classifying lesions with a mixed component of patterns (kappa = 0.13). Agreement was better using the modified cytonuclear grading scheme (kappa = 0.57), with most consistency achieved using the Van Nuys scheme (kappa = 0.66). Most discordant results using the later scheme were due to inconsistency in assessing the presence or absence of luminal necrosis. CONCLUSIONS: Both the new classification schemes assessed in this study were an improvement over the traditional architectural classification system for ductal carcinoma in situ, and resulted in more reproducible pathological assignment of cases. The Van Nuys classification scheme is easy to apply, even to small areas of carcinoma, resulting in acceptable interobserver agreement between reporting pathologists. Additional work will be required to arrive at a consensus definition of necrosis for cases in the non-high-grade group.

The presence of atypical small acinar proliferation in prostate needle biopsy is predictive of carcinoma on subsequent biopsy

Objective To determine the clinical significance of nondiagnostic small acini showing cellular atypia (atypical small acinar proliferation) in prostatic biopsies of patients with clinical findings suggestive of malignancy.

Chronic exposure to schistosome eggs reduces serum cholesterol but has no effect on atherosclerotic lesion development

Previous studies have shown that people infected with schistosomiasis have lower levels of serum cholesterol than uninfected controls. To better understand the impact of this parasitic infection on serum cholesterol levels and on atherosclerotic lesion development induced by hypercholesterolemia, apolipoprotein E (ApoE)‐deficient mice were chronically exposed to the eggs of Schistosoma mansoni over a period of 16 weeks. Total serum cholesterol and low‐density lipoprotein (LDL) were reduced in egg‐exposed ApoE‐deficient mice fed a diet high in cholesterol compared to unexposed controls. However, exposure to eggs had no effect on atherosclerotic lesion size or progression in ApoE‐deficient mice. Macrophages isolated from egg‐exposed mice had an enhanced ability to take up LDL but not acetylated LDL (acLDL). This study suggests that schistosome eggs alone may alter serum lipid profiles through enhancing LDL uptake by macrophages, but these changes do not ultimately affect atherosclerotic lesion development.

Fine needle aspiration cytodiagnosis of secretory carcinoma of the breast

Secretory carcinoma (SC) of the breast is a rare variant of breast malignancy and its cytological features in fine needle aspirates have only recently been described. In this communication, our experience with four cases of SC of the breast is presented in which the diagnosis was established on fine needle aspiration cytology (FNAC). In all cases, the samples were cellular and featured diffuse, prominent, intracytoplasmic vacuoles and secretion in malignant cells and occasional signet‐ring like forms. The cytodiagnosis of SC in all the cases correlated with subsequent examination of cell blocks of the aspirate and tissue. Cytochemical stains showed diffuse positivity for mucin by alcian blue stain in the vacuolated cells which was periodic acid–Schiff positive and resistant to diastase digestion. Oil‐red O staining was negative. Immunopositivity to carcinoembryonic antigen, cytokeratin (CAM 5.2), B72.3 and epithelial membrane antigen was found in malignant cells. The cytodiagnostic criteria for SC of the breast, characteristic cytological features which are useful in a correct FNAC diagnosis and differentiation from other pertinent breast carcinomas, are discussed.

Protection from EAE by IL-4Rα-/- macrophages depends upon T regulatory cell involvement

The administration of Th2 cytokines or immune deviation to a Th2 phenotypic response has been shown to protect against the autoimmune pathology of experimental autoimmune encephalomyelitis (EAE). To better understand the function of Th2 cytokines in the induction stage of EAE in the absence of an overt Th2 response, we immunized IL‐4 receptor alpha‐deficient (IL‐4Rα−/−) mice, which are unable to respond to either IL‐4 or IL‐13. Contrary to expectations, mice lacking IL‐4Rα had a lower incidence of EAE and a delayed onset compared to WT BALB/c mice; however, this delay did not correlate to an alteration in the Th1/Th17 cytokine balance. Instead, IL‐4Rα‐responsive macrophages were essential promoters of disease as macrophage‐specific IL‐4Rα‐deficient (LysMcreIL‐4Rα−/lox) mice were protected from EAE. The protection afforded by IL‐4Rα‐deficiency was not due to IL‐10‐, IFN‐γ‐, NO‐ or IDO‐mediated suppression of T‐cell responses but was dependent upon the presence of regulatory T cells (Tregs). This investigation highlights the importance of macrophages and Tregs in regulating central nervous system inflammation and demonstrates that macrophages activated in the absence of Th2 cytokines can promote disease suppression by Tregs.

Aspiration cytodiagnosis of small cell malignancies found in fine needle aspirate (FNA) of the liver: an immunocytochemical study

In this study the features of small cell malignancies found in the liver by fine needle aspiration cytology (FNAC) and immunostains required for a diagnosis and differential diagnosis are presented. The material consisted of 197 fine needle aspirates which were performed under image guidance between January 1982 to October 1999. Of these, 30 were diagnosed as small cell malignancies. The age of patients ranged between 46 and 68 years. The aspirated material was examined using Papanicolaou‐stained filter preparations and cell blocks, the latter stained with hematoxylin and eosin and a panel of immunoperoxidase stains. The diagnoses based on a correlation of relevant clinical history, cytohistological findings and immunostaining were: metastatic small cell anaplastic carcinoma of lung (n = 6); neuroendocrine tumour (n = 9); non‐Hodgkins lymphoma (n = 4); well‐differentiated cholangiocarcinoma (n = 2); metastatic carcinoma of the prostate (n = 2); metastatic adenocarcinoma (n = 4) and metastatic carcinoma breast (n = 3). This study emphasizes the wide range of neoplasms that enter into the differential diagnosis of small cell malignancies found in the liver and a correlation of clinical, cytohistological and immunostaining findings which seem to be useful in suggesting a diagnosis.

The usefulness of a panel of immunostains in the diagnosis and differentiation of metastatic malignancies in pericardial effusions

Pericardial effusions are not uncommon in patients with an advanced malignancy. Rarely malignancies may present initially with a pericardial effusion. Cytological examination of pericardial fluid may be valuable in differentiation of these cases. However, a metastatic tumour in serous effusion may not always show the functional differentiation of the primary tumour. In such a situation, although a wide range of special studies have been suggested for the diagnosis of malignancy we have found the use of a panel of a few common immunostains to be useful in confirming or suggesting the site of a primary tumour. The material for this study consisted of 76 pericardial fluids obtained between January 1991 and October 1998 from 46 males (mean age 59 years) and 30 females (mean age 52 years). Metastatic malignancy was diagnosed in 22 of the 76 patients and in 7/22 cases pericardial effusions were the initial presentation. The subsequent follow‐up in the seven cases revealed adenocarcinoma of lung (n = 2), small cell anaplastic carcinoma of lung (n = 1), squamous cell carcinoma lung (n = 1), melanoma leg (n = 1), non‐Hodgkin’s lymphoma retroperitoneal lymph nodes (n = 1) and carcinoma of the breast (n = 1). Of the remaining 15 cases with a known history of malignancy, eight had cancers (three adeno; two small cell; one poorly differentiated, and two squamous cell types) of the lung; breast (n = 3); colon (n = 1); melanoma (n = 2) and non Hodgkin’s lymphoma (n = 1). Immunostains which were useful in the diagnosis were EMA, CEA, cytokeratin, B72.3, HMB45, vimentin, S100, LCA, L26 and kappa and lambda light chains.

Vasculitis-induced colonic strictures

PURPOSE: The clinical presentations of gastrointestinal involvement from systemic vasculitis are diverse. Colonic involvement from systemic vasculitis is unusual. We report the first case of a symptomatic colonic stricture associated with rheumatoid vasculitis and another associated with systemic lupus erythematosus. METHODS: The clinical, radiologic, and histologic features of two cases of symptomatic colonic strictures secondary to colonic involvement with vasculitis are described. The literature covering gastrointestinal involvement from vasculitis in these conditions is reviewed. RESULTS: Surgical resection of the colonic strictures was required in both patients and had a satisfactory outcome. CONCLUSIONS: These cases provide further evidence of the protean clinical presentations of intestinal involvement in systemic vasculitis. Although immunosuppression has been shown to be of value in the treatment of vasculitis affecting the gastrointestinal tract, surgical resection is required for established strictures.

Malignant mixed mullerian tumour of the fallopian tube occurring in a patient with Peutz–Jegher's syndrome

Peutz–Jegher’s syndrome (PJS) is an inherited condition in which patients develop multiple hamartomatous polyps of the gastrointestinal tract and mucocutaneous pigmentation affecting the mouth. In addition, PJS predisposes to cancer, the most common malignancies being those of the small and large intestines, stomach and pancreas. Females with the syndrome are also at increased risk for breast cancer and tumours of the genital tract including adenoma malignum of the cervix and various tumours of the ovaries including mucinous cystadenomas, granulosa cell tumours and sex cord tumour with annular tubules. The fallopian tube may also be affected, the most common lesion being mucinous metaplasia. To our knowledge, malignant mixed mullerian tumour (MMMT) of the fallopian tube has not previously been described in association with PJS.

Elasticity of abdominal wall vessels in children: clinical implications in child abuse

Abdominal trauma secondary to non‐accidental injury is associated with high rates of morbidity and mortality. It has been noted that children who have suffered abusive abdominal injuries often lack abdominal wall bruising. We hypothesize that children have highly elastic vessels that stretch instead of rupturing when the abdomen is punched. Our study investigates the degree of elasticity in abdominal wall vessels in young children.