Castleman Disease and Rosai-Dorfman Disease.

This chapter describes the main features of two different diseases, Castleman Disease (CD) and Rosai-Dorfman Disease (RDD). Castleman disease (CD) is a clinical and histopathologically heterogeneous lymphoproliferative disorder that encompasses at least three distinct entities with some common overlapping morphological features: Hyaline Vascular CD (HVCD), Unicentric Plasma Cell CD and Multicentric CD. The most important feature of HVCD is the presence of abnormal germinal centers with hyaline-vascular transformation, sometimes showing multiple germinal centers within a single reactive lymphoid follicle, this outlining HVCD as a disorder of follicular dendritic cells. Unicentric and multicentric CD are, in contrast, lymphoproliferative lesions. Proinflammatory hypercytokinemia is an essential feature of multicentric CD, distinguished by a florid clinical presentation. Rosai-Dorfmann Disease is a histiocytic proliferative disorder diagnosed by the presence of tissue infiltration by S100-positive CD1a-negative histiocytes and plasma cell aggregates, often with Russell bodies. A typical, though not specific, characteristic of the disease is emperipolesis. Initially considered to be an inflammatory/reactive condition, molecular studies suggest that at least some cases of RDD could be considered as a low-grade histiocytic neoplastic process.

Tactile Corpuscle-like Bodies in Gastrointestinal-type Mucosa: A Case Series.

Tactile corpuscle-like bodies (TCLB) are microscopic Schwannian structures that simulate the superficial mechanoreceptors of the peripheral nervous system (Wagner-Meissner corpuscles). They have been described nearly exclusively in peripheral nerve sheath tumors, namely diffuse neurofibromas, and schwannomas but also in cellular nevi. There are rare reports of these structures in the gastrointestinal tract (predominantly the lower tract), with the presumption that they are incidental reactive neural proliferations. We compiled 9 cases showing this rare phenomenon in gastrointestinal-type mucosa in nonsyndromic patients to further characterize its features. There were 6 men and 3 women (age range, 39 to 79 y, mean 56 y) with lesions involving esophagus/gastro-esophageal junction (n=7), sigmoid colon (n=1), and gastric heterotopia of the cricopharynx (n=1). Endoscopic examination was abnormal in 6 of the 7 cases (including changes consistent with Barrett esophagus and polypoid/nodular mucosa) and normal in 1 of 7 cases for which this information was available. The histologic features were similar in all cases, with unencapsulated clusters of lamellated and concentrically arranged spindle cells in the lamina propria. The foci of TCLB ranged in size from <0.1 to 1.5 mm in the greatest dimension. Abnormal histopathologic findings were identified in the background mucosa in 6 of 9 cases (including Barrett esophagus, active and inactive chronic gastritis, enterochromaffin-like cell hyperplasia, and gastric intestinal metaplasia). None of the patients showed signs of neurofibromatosis type 1, multiple endocrine neoplasia type 2B, Cowden syndrome, or other inherited syndrome. No morbidity related to TCLB was reported for the patients with available follow-up.

A clinical model for predicting lymph node metastasis in submucosal invasive (T1) colorectal cancer.

BACKGROUND: No single histopathological feature of submucosal invasive colorectal cancer (T1-CRC) can reliably predict the risk for lymph node metastasis (LNM). AIM: The purpose of the study was to develop a prediction model of LNM in T1-CRC. METHODS: Ninety-seven surgically resected T1-CRC at our institution were retrospectively evaluated. Morphology, localization, grading, mode of growth, presence of background adenoma, lymphoid infiltration, angiolymphatic invasion, budding, and depth of invasion were assessed. Mortality and morbidity related to surgery were also evaluated. Benefit-risk balance was assessed according to the presence of severe complications and to the presence of LNM. RESULTS: Fourteen cases had LNM (14%). Eight patients (8%) presented severe surgical complications and there were two deaths (2 %). Infiltrative growth pattern (OR 31.91, 95% CI 2.37-428.36; p = 0.009) and the absence of lymphoid infiltrate (OR 28.75; 95% CI 2.13-388.37; p = 0.011) were the only variables independently associated with LNM in the multivariate analysis. Both variables were included in the prediction model together with sessile morphology (OR 4.88; 95% CI 0.81-29.3; p = 0.083) and poorly differentiated carcinoma (OR 11.77; 95% CI 0.77-179.83; p = 0.076). A 0-100 score was developed (infiltrative growth pattern: no = 0, yes = 33; lymphoid infiltrate: no = 29, yes = 0; sessile morphology: no = 0, yes = 15; poorly differentiated: no = 0, yes = 23). Cutoff point to indicate additional surgery was set in 35 points (i.e., 10% risk LNM). Discrimination of the prediction model was excellent (AUC 0.90; 95% CI 0.81-0.99). CONCLUSION: Combined evaluation of infiltrative growth pattern, lymphoid infiltration, poorly differentiated carcinoma, and sessile appearance showed good performance for discriminating T1-CRC patients with LNM. The benefit-risk balance was in favor of surgery when at least two of these criteria were present.

Viral-associated trichodysplasia secondary to antineoplastic treatment in a patient with lymphoblastic leukemia.

Viral-associated trichodysplasia spinulosa is an unusual condition with distinctive clinical and histopathological features. Initially described in patients immunosupressed as a result of solid organ transplantation, it has also been reported in patients treated with immunosuppressive drugs other than cyclosporine or being treated for hematological malignancies. Patients presented with disseminated follicular, hyperkeratotic papules, and variable degrees of alopecia. Histopathological examination revealed shaftless bulbous and dilated hair follicles with keratotic plugging of the infundibulum. The authors reported a case of viral-associated trichodysplasia in a 5-year-old boy treated for a lymphoblastic leukemia. Eruption persisted, although treated with emollients and keratolytics, but resolved spontaneously after completing the antineoplastic medication.

Family history and breast cancer hormone receptor status in a Spanish cohort.

BACKGROUND: Breast cancer is a heterogenous disease that impacts racial/ethnic groups differently. Differences in genetic composition, lifestyles, reproductive factors, or environmental exposures may contribute to the differential presentation of breast cancer among Hispanic women. MATERIALS AND METHODS: A population-based study was conducted in the city of Santiago de Compostela, Spain. A total of 645 women diagnosed with operable invasive breast cancer between 1992 and 2005 participated in the study. Data on demographics, breast cancer risk factors, and clinico-pathological characteristics of the tumors were collected. Hormone receptor negative tumors were compared with hormone receptor postive tumors on their clinico-pathological characteristics as well as risk factor profiles. RESULTS: Among the 645 breast cancer patients, 78% were estrogen receptor-positive (ER+) or progesterone receptor-positive (PR+), and 22% were ER-&PR-. Women with a family history of breast cancer were more likely to have ER-&PR- tumors than women without a family history (Odds ratio, 1.43; 95% confidence interval, 0.91-2.26). This association was limited to cancers diagnosed before age 50 (Odds ratio, 2.79; 95% confidence interval, 1.34-5.81). CONCLUSIONS: An increased proportion of ER-&PR- breast cancer was observed among younger Spanish women with a family history of the disease.

BRCA1 mutations do not increase prostate cancer risk: results from a meta-analysis including new data.

BACKGROUND: Although in recent years deleterious BRCA1 mutations have been extensively studied as a prostate cancer risk factor, results are inconclusive. To assess the contribution of the BRCA1 Galician founder mutation c.211A>G in prostate cancer morbidity we conducted a case-control study. Moreover, to better elucidate whether deleterious BRCA1 mutations are involved in the development of prostate cancer, we performed a systematic review and a meta-analysis of BRCA1 studies on prostate cancer. METHODS: A total of 905 unselected men diagnosed with adenocarcinoma of the prostate and a control group of 936 unrelated men without history of prostate cancer were evaluated for c.211A>G. Adjusted by age Odds ratios (OR) and 95% confidence intervals (CIs) were estimated using logistic regression. To construct the meta-analysis, genotype-based epidemiological studies reporting BRCA1 founder mutations on prostate cancer were identified by comprehensive and systematic bibliographic search. After extraction of relevant data, main and subgroup analysis by mutation were performed to assess the effect of BRCA1 on prostate cancer risk. RESULTS: Four c.211A>G heterozygous individuals, one patient and three controls, were detected (OR = 0.27; 95% CI: 0.01-2.36; P = 0.28). Meta-analysis results from the integration of our data and other seven studies with BRCA1 genotyping data (5,705 prostate cancer cases and 13,218 controls) did not detect an association with prostate cancer risk (OR = 1.36; 95% CI: 0.87-2.14; P = 0.18). CONCLUSIONS: Our conclusive trial demonstrates the lack of association between Galician splicing mutation c.211A>G in the BRCA1 gene and prostate cancer risk. Moreover, the result of the meta-analysis also discards the involvement of BRCA1 mutations in the development of prostate cancer.

Pharmacogenetic analysis in neoadjuvant chemoradiation for rectal cancer: high incidence of somatic mutations and their relation with response.

AIMS: The identification of predictive markers of response to chemoradiotherapy treatment remains a promising approach for patient management in order to obtain the best response with minor side effects. Initially, we investigated whether the analysis of several markers previously studied and others not yet evaluated could predict response to 5-fluorouracil- and capecitabine-based neoadjuvant treatment in locally advanced rectal cancer. METHODS & MATERIALS: We studied germline and tumoral samples of 65 stage II/III rectal patients. A panel of pharmacogenetic markers was genotyped in paired peripheral blood samples and rectal cancer tumors. RESULTS: Our results seem to confirm the previously described association of thymidylate synthase and the prediction of chemoradiotherapy response in rectal cancer. However, it failed to confirm the clinical utility proposed for XRCC1, ERCC1, ERCC2, MTHFR and EGFR polymorphisms in blood/germline samples. Subsequently, with the aim of improving prediction of individual response and assessing the role of studied polymorphisms in response to treatment, we determined if changes in tumor response to these markers could predict clinical outcome. We found a high degree of changes between germline and tumor samples, mainly somatic mutations without microsatellite instability, and a minor frequency of loss-of-heterozygosity events. In tumoral samples, XRCC1 appeared to be significantly associated (p = 0.006) with downstaging of the tumor (odds ratio: 7.93; 95% CI: 1.03-60.83), but the increasing of TYMS low-expression alleles contradict the previous results observed in germline samples. CONCLUSION: The detection of somatic mutations in rectal cancer tumors led us to re-evaluate the utility of the tests performed in blood samples for these polymorphisms in rectal cancer. Furthermore, studies aimed at assessing the influence of pharmacogenetic markers in treatment response performed in blood samples should take into account the particular pattern of hypermutability present in each tumor type. We hypothesize that different patterns of hypermutability present in each tumor type would be related to the different results in association studies related to response to the treatment.