Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

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The Armed Forces Institute of Pathology.

Hodgkindisease (HD) is characterized by a small numberofputativemalignant cells [HodgkinandReed-Sternberg (HRS) cells] among a background of lymphocytesandhistiocytes. The lineage ofHRS cells is still elusive anda clonal origin of these rare cells hasnot formally been demon-strated. Weisolated HRScells by micromanipulation fromhistologicalsectionsofthreecasesofHodgkinlymphoma(eachrepresenting a distinct subtype of the disease) and analyzedindividual cells for immunoglobulin variable (V) gene rear- rangements by PCR. In each of the three cases a singieheavy-chain V (VH) (and in one case, in addition, a K light-chain)generearrangement was amplifiedfromtheHRScells, identifying these cells as membersof a single done. A poten-tiallyfunctionalVHrearrangement was obtainedfrom acase ofnodular sclerosis HD. Somatic mutations and intraclonal di- versity in the VHgenesindicate a germinal center B-cell originof the HRScells in a case of lymphocyte-predominant HD,whereas ina caseof mixed-cellularity

Hodgkin disease: Hodgkin andReed-Sternberg cells picked from histological sections showclonal immunoglobulin gene rearrangements andappear tobederived fromB cells atvarious stages ofdevelopment

On tumors of the salivary glands.

Characteristics and outcomes according to molecular subtypes of breast cancer as classified by a panel of four biomarkers using immunohistochemistry

Background The characteristics of the cellular kinetic reflect the aggressiveness of the tumors and even their prognosis, many studies proving the correlation between the increased proliferation activity and a poor prognosis in a variety of neoplasms. Aim The analysis of immunohistochemical expression of the Ki-67 antigen using the monoclonal antibody MIB1 in 61 patients with gastric cancer, the correlation with clinicopathological factors and the prognosis of the patients. Material and methods We used the primary MIB1 antibody pre-diluted, using the LSAB technique, DAB visualization. The quantification of the reaction was performed by appreciating the marking index Ki-67 (MI Ki-67). Although all the lesions were positive, we noticed a marked intratumoral heterogeneity regarding the distribution of the Ki-67 score. The tumor cells were considered Ki-67 positive in the presence of brown nuclear staining of granular or diffuse type. The tumor invasion front has shown the most numerous Ki-67 positive cells. Results In the gastric carcinomas, we remarked various Ki-67 scores. For a proper grouping of the results, we classified gastric carcinomas into two categories: carcinomas with high MI Ki-67 (≥45%) and carcinomas with low MI Ki-67 (≤45%). We noticed an increased frequency of high MI Ki-67 carcinomas in elderly patients (p=0.03) and also in the tumors developed at cardia level and those extended in the entire stomach in the moment of diagnosis (p 0.05). Conclusions In our study, immunohistochemical assessment of the tumor proliferation does not represent a prognostic factor, but seems to be useful in identifying of a group of patients with aggressive tumors, needing adjuvant postoperatory chemotherapy.

Ki-67 expression in gastric cancer. Results from a prospective study with long-term follow-up

BACKGROUND The aim of our study is to investigate the immunohistochemical expression of E-cadherin in gastric carcinomas and in surrounding mucosa (normal or with lesions of chronic atrophic gastritis, intestinal metaplasia or dysplasia). MATERIAL AND METHODS We included 61 patients with gastric cancers operated in Emergency County Hospital Timisoara. We analyzed the E-cadherin immunohistochemical expression, the correlation with clinical and pathological factors and the outcome of the patients. The positive homogeneous pattern of staining for the cellular membranes is considered normal. The negative homogeneous or the heterogeneous pattern (of the cytoplasm and membrane) represented aberrant E-cadherin expression. RESULTS Areas of chronic atrophic gastritis and intestinal metaplasia presented a normal pattern of immunostaining for the membranes. Aberrant E-cadherin expression was noticed in 30 cases of gastric carcinomas (49.2%) and in 11 cases (35.5%) of epithelial dysplasia in the surrounding tissue. Our results showed no correlation between E-cadherin expression and gender, age, tumor location, pT, pN, pTNM and lympho-vascular invasion. Aberrant E-cadherin immunostainings were significantly more frequent in diffuse-type carcinomas in comparison with the intestinal-type carcinomas (82.4% vs. 31.6%) (p = 0.000491 ES). Signet-ring carcinomas and anaplastic carcinomas presented a high-proportion of aberrant immunostainings (82.4% and 100%), as well as poor differentiated carcinomas (61.5%). Carcinomas with distant metastasis presented significantly more aberrant immunostainings than those without metastasis (71.4% vs. 42.6%). Five-year survival rate was significantly lower in patients with aberrant E-cadherin expression in comparison with the patients presenting normal staining (10% vs. 22.6%). CONCLUSIONS In gastric carcinomas and areas of epithelial dysplasia, aberrant E-cadherin expression was significantly more frequent in comparison with the surrounding normal mucosa (p<0.001 ES). Our data suggest a strong correlation between Lauren's classification of gastric carcinomas and E-cadherin immunohistochemical expression. Assessment of the survival curve of the patients highlighted the role of prognostic factor for the aberrant immunohistochemical E-cadherin expression.

The immunohistochemical expression of E-cadherin in gastric cancer; correlations with clinicopathological factors and patients' survival.

Purpose In the last years, the incidence of breast cancer has been increasing; characteristic patterns of gene expression have emerged, reflecting molecular differences between previously known as well as newly defined subtypes of breast cancer. This study aimed to classify the molecular subtypes of breast cancers based on the expression profile of immunohistochemical markers and to evaluate their association with clinicopathological features. Material and methods A total of 173 cases of breast carcinoma were examined retrospectively using immunostains for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2). Because the triple-negative phenotype, when defined by IHC using only these three markers, is not the optimal method for defining basal-like breast cancer, we need to use an additional marker--CK 5/6. Results The luminal type was the most common subtype in breast cancer (71.6%), which was followed by the basal subtype (21.9%). HER2 subtype were 2.8% from the total of cases, being associated with the highest rate of high-graded cases. Basal type is presented largely in premenopausal women and displayed aggressive features, such as large tumor size and poorly differentiated cancers. Luminal A included the highest percentage of patients older than 60 years, the highest proportion of stage I-II tumors and well/moderately differentiated lesions. HER2-type was more frequent in premenopausal women and showed a high percentage of positive lymph nodes. Conclusions These molecular differences have been shown to correlate very well with clinical features and survival, or even better than traditional histopathological parameters. The discovery of certain molecular characteristics of breast cancers has helped us to understand better the pathophysiology of disease and to develop more direct therapeutic strategies.

Clinicopathologic features and five years survival analysis in molecular subtypes of breast cancer.

Warthin tumor was first described in the American literature, by Aldred Warthin, in 1929, the pathologist who named this tumor papillary cystadenoma lymphomatosum, but since than it was also knew as adenolymphoma, cystadenolymphoma, and Warthin tumor. Because of its microscopically appearance and unknown origin, this tumor entity is still fascinating head and neck surgeons and pathologist. We evaluate the histopathological aspect of Warthin tumors using Hematoxylin-Eosin stain, and immunohistochemical and histological techniques. We reviewed the medical record of patients with salivary gland tumors diagnosed at County Hospital of Timisoara from 2002-2008. In six years, 22 cases with Warthin tumor were diagnosed and among them 17 men and five women, with average age 58.47. The analysis showed that 77.27% of Warthin tumors occurred in men, and the main histopathological aspect was with 50% epithelial component. The stromal component showed a prominent B-cell population by staining with CD20, and histological techniques for mucin were positive, and reticulin fibers were revealed while using Gordon-Sweets stain. The standard and the histological and immunohistochemical techniques highlighted the complex and variable microscopical appearance of Warthin tumor that the pathologist should consider when a diagnosis for this tumor is to be considered.

Warthin tumor: a curious entity--case reports and review of literature.

PURPOSE The purpose of this study was to identify the clinicopathological factors that influence the prognosis of patients having undergone surgery for gastric cancer The analysis of the potential prognosis factors has included in this study parameters concerning the patient (sex, age), as well as parameters related with the tumor (histological type according to the WHO classification; degree of tumor differentiation; tumor location; stage of disease; pT and pM parameters according to the TNM classification of AJCC/UICC) MATERIAL AND METHODS From the total number of 265 patients (186 men and 79 women) diagnosed with gastric cancer in the period 1998-2002, 61 operated patients were selected On this group, we performed a prospective study regarding the evolution and aggressiveness of gastric cancer, on a duration of 5 years Survival time was calculated from the month of the surgical intervention until the month of death or confirmation of survival, and survival rate was represented by the percentage of survivals at the end of the observed interval (in years and months) RESULTS The studied group consisted of 61 patients (43 men and 18 women), with ages between 30 and 80 (average age = 5934 years) According to the maximum level of tumor invasion we identified: pTis - one case (16%); pT1 - four cases (66%); pT2 - nine cases (147%); pT3 - 17 cases (279%); most gastric cancers were included in the pT4 category (492%) We identified 43 gastric carcinomas with metastases in regional lymph nodes (705% of the cases) According to the number of lymph nodes involved: pN0 - 18 cases (295%); pN1 - 16 cases (262%); pN2 - 23 cases (377%); pN3 - four cases (66%) Distance synchronous metastases were present in 14 gastric carcinomas (pM1 - 23% of the cases), nine cases with hepatic metastases and five cases with distance peritoneal disseminations Classification of gastric carcinomas: we identified one single case listed in the 0 stage, three cases in the IA stage, five cases in the IB stage, seven cases in the II stage, 11 cases in the IIIA stage, eight cases in the IIIB stage, and 26 cases in the IV stage From the total of carcinomas, stage IV consisted of the greatest number of tumors, representing 426% We generally remarked the increase of the number of cases in advanced stages CONCLUSIONS In the studied group, we noted a great number of gastric carcinomas diagnosed in stages T3 and T4 (771% of cases) Cardial tumor locations and gastric stump locations, as well as "signet-ring" cell and undifferentiated carcinomas prove to be aggressive, being diagnosed in advanced stages 705% of gastric neoplasms presented lymph node metastases, most cases representing pN2 tumors (377%) 23% of neoplasms studied presented distance metastases at the time of diagnosis We noted a significant correlation between the degree of tumor differentiation and the level of invasion, as well as the presence of distance and lymph node metastases Survival at 5 years of patients included in the study was correlated significantly with the level of tumor invasion, the presence of lymph node and distance metastases, and the TNM stage

Elena Lazăr

Papers

Ki-67 expression in gastric cancer. Results from a prospective study with long-term follow-up

The immunohistochemical expression of E-cadherin in gastric cancer; correlations with clinicopathological factors and patients' survival.

Clinicopathologic features and five years survival analysis in molecular subtypes of breast cancer.

Warthin tumor: a curious entity--case reports and review of literature.

Gastric cancer: correlation between clinicopathological factors and survival of patients (III).