Diagnostische Fallstricke beim Cushing-Syndrom

Adrenal cortical carcinoma is a rare diagnosis and may present with hormone secretion. A histological differentiation between an adrenal cortical adenoma and carcinoma can be very difficult. However, a fast diagnosis including staging and complete surgical resection is pivotal for the prognosis of an adrenal cortical carcinoma. Metastasing adrenal cortical carcinoma should be treated with a mitotane based chemotherapy, and inclusion in the “firm-act study” is highly recommended. The present case report demonstrates the diagnostic pitfalls in a female patients with Cushing’s syndrome who suffered from metastasing adrenal cortical carcinoma.     

Immunological characterization of mononuclear cells and morphological findings in patients with mammary carcinoma

Summary Mononuclear cells from peripheral blood and draining lymph nodes of 40 patients with invasive mammary carcinoma were examined for various immunological cell surface markers including surface membrame immunoglobulins and rosetting properties (E, EA, EAC). No significant relationship could be established to anyone of the following criteria for which the literature reports varying prognostic values: Clinical staging of the disease, histological tumor type, grading, nuclear differentiation, round cell infiltration, perivenous infiltration, sinus histiocytosis, and lymph node reaction patterns (lymphocyte predominance, germinal center predominance, lymphocyte depletion, unstimulated nodes). From the reported results it is concluded that the analysis of lymphocyte cell surface markers in mammary carcinoma is not a suitable parameter for supporting the existence of specific or unspecific anti-tumor immune reactions which may be suspected from certain histological reaction patterns     

Prenatal Diagnosis of Giant Left Ventricular Diverticulum: Case Report

The distinction between a ventricular aneurysm and diverticulum is difficult. The differences between these two are based on anatomical, histological, and functional criteria. We present a case of prenatal diagnosis of a giant left ventricular outpouching at 28 weeks gestation. During the postnatal period, the neonate underwent surgical correction for the outpouching. Histopathological examination reported the resected segment was a cardiac diverticulum. Our case indicates that differentiating between the two diagnoses during the intrauterine period is not always straightforward and possible. Histopathological examinations are sometimes necessary to make a precise differentiation. Treatment should be individualized depending on the clinical presentation.     

Colorectal carcinoma: histopathological diagnosis and staging

It is possible to make a histopathological diagnosis of colorectal carcinoma from ulcerating lesions by means of forceps biopsy, but this presents problems in polypoid tumours. In order to make the diagnosis of invasive carcinoma, evidence of invasive growth into the submucosa is necessary. In polypoid tumours, this can be done usually only by endoscopic or surgical polypectomy. In addition to histopathological diagnosis, one of the most important tasks for the contemporary pathologist is the exact classification of colorectal tumours. The most important parameters are typing, grading, staging and the R classification, i.e. the assessment of presence or absence of residual tumour following treatment. Typing and grading is done according to the WHO recommendations; the great majority of colorectal carcinomas are adenocarcinomas or mucinous adenocarcinomas. In grading, one can differentiate into either four grades (G1 to 4) or between low and high grade. The internationally accepted TNM/pTNM system, as described in the 4th edition, is used for staging. This system has considerable advantages over the traditional, but often misused Dukes' classification. After treatment, the surgeons and the pathologists must work together to determine the R classification. Typing, grading and staging are of great importance in deciding on the indication for either a limited surgical procedure or a radical resection. Together with the R classification, they decisively influence the indications for post-treatment after surgical therapy. R classification is the most important factor for prognosis after surgical removal of tumours. Following resection for cure, the prognosis is especially affected by the pTNM classification and its corresponding stages. The independent prognostic significance of other clinical, macroscopic and histological findings cannot yet be definitively determined.     

Classification of thyroid follicular cell tumors: with special reference to borderline lesions

We propose a new classification of thyroid follicular cell tumors which is correlated with patient's prognosis. It is unique as to two new categories: borderline malignancy between benign and malignant, and moderately differentiated adenocarcinoma (MDA) as a differentiation classification to stratify tumor aggressiveness. As to diagnostic criteria, we recommend invasiveness (capsular and vascular invasion) to separate benign and malignant and it should not be based on presence or absence of papillary thyroid carcinoma (PTC) type nuclear features (PTC-N). Thus borderline malignancy in our new classification includes some of the formerly malignant tumors and they are 1) papillary microcarcinoma, 2) encapsulated conventional PTC (EncPTC), 3) encapsulated follicular variant PTC (EnFVPTC), 4) well differentiated tumor of uncertain malignant potential (WDT-UMP), 5) follicular tumors of uncertain malignant potential (FT-UMP), and 6) capsular invasion only follicular thyroid carcinoma (FTC). Review of the literature revealed that those thyroid tumors have consistently excellent outcome. Well differentiated follicular cell adenocarcinoma (WDA) in our classification includes common type PTC and low-risk follicular carcinoma (FTC). They are invasive (diffuse infiltrative) common type PTC and minimally invasive type FTC with less than 4 foci of angioinvasion. Moderately differentiated follicular cell adenocarcinoma (MDA) includes FTC with angioinvasion (more than 4), aggressive variants of PTC, such as tall cell, columnar cell, solid, loss of cellular polarity/cohesiveness (hobnail) variants and encapsulated carcinoma with high grade histology. Poorly differentiated carcinoma (PDC) includes PDC of WHO definition, insular carcinoma, tumors with minor anaplastic transformation and tumors with distant metastasis at presentation.     

Relationship between microvessel density and telomerase activity in hepatocellular carcinoma

AIM: To study the relationship between microvessel density (MVD), telomerase activity and biological characteristics in hepatocellular carcinoma (HCC). METHODS: S-P immunohistochemical method and telomeric repeat amplification protocol (TRAP) were respectively used to analyze the MVD and telomerase activity in 58 HCC and adjacent normal tissues. RESULTS: The MVD in HCC with metastasis, lower differentiation or without intact capsule was significantly higher than that in HCC with intact capsule, higher differentiation, or without metastasis. While MVD had no relationship with tumor size, hepatic virus infection and other clinical factors. Telomerase activity was related to differentiation degree, but not to tumor size or histological grade. MVD in HCC with telomerase activity was higher than that in HCC without telomerase activity. CONCLUSION: MVD and telomerase activity may serve as diagnostic criteria of HCC in earlier stage. Meanwhile, there may be a cooperative effect between MVD and telomerase on the growth and metastasis of HCC.     

The colorectal malignant polyp: scoping a dilemma.

Colorectal adenomas containing invasive carcinoma represent the majority of early colorectal cancers. The malignant polyp carries a significant risk of lympho-haematic metastasis and mortality due to the penetration of cancerous cells into the submucosal layer. The therapeutic dilemma is whether to perform endoscopic or surgical resection. A thorough assessment of the endoscopic, histological and clinical variables is needed to unravel the best treatment for each patient. In particular, a unique staging of such lesions, based on certain histopathological features, has been deeply implicated in the therapeutic choice. Aim of this article is to review the main endoscopic, histological and clinical features of the malignant polyp in order to propose a systematic management of this lesion.     

A case report of cribriform carcinoma of the pancreas with long time survival

A 62-year-old man had complained of left abdominal pain and tenderness and a body weight loss. Abdominal ultrasonography and computed tomography revealed homogeneous tumor with clear margin, and an irregular shape (3.5 x 2.0 cm) in the body of the pancreas. Endoscopic retrograde cholangiopancreatography showed a shadow defect in the main pancreatic duct adjacent to the tumor, which suggested intraductal tumor spread. Distal pancreatectomy with splenectomy and left paraaortic lymph node dissection was performed. Microscopically, the tumor showed microtubular carcinoma, which was characterized by a cribriform pattern, medullary growth, and little interstitium. The tumor was encapsulated by a relatively thick fibrous capsule. The patient was discharged uneventfully, and he is alive 33 months after operation without a distinct sign of recurrence. In conclusion, cribriform carcinoma of the pancreas has specific characteristics, such as good prognosis, expansive growth with little invasion, intraductal growth and spread without mucin production and histological marked cribriform pattern. This type of carcinoma should be classified as a new disease entity of carcinoma of the pancreas.     

The Stem Cell Marker Bmi-1 Is Sensitive in Identifying Early Lesions of Carcinoma ex Pleomorphic Adenoma

In the present study, we evaluated and described the sensitivity of the stem cell marker B cell-specific moloney murine leukemia virus integration site 1 (Bmi-1) in identifying early lesions of carcinoma ex pleomorphic adenoma (CXPA). While invasive CXPAs are tumors with a prominent and easily recognizable malignant component, the identification of early carcinomatous changes in PA remains a diagnostic challenge due to the lack of objective morphological criteria. The immunohistochemical expression of Bmi-1 was assessed in both adenomatous and carcinomatous components of 9 CXPA cases at an early phase of histological progression (6 intracapsular and 3 minimally invasive) grouped according to the cellular differentiation as luminal (7 cases) or myoepithelial (2 cases). A selective nuclear expression of Bmi-1 was found exclusively in the malignant component of 8 cases (6 luminal type and 2 myoepithelial type), including intraductal carcinoma areas, except for 1 case in which scarce cells of the remnant PA were positive. Thus, Bmi-1 is expressed from the earliest morphologically detectable stages of PA malignant transformation. When faced with atypical features in PA, evaluation of Bmi-1 expression can provide more objective criteria for identification and diagnosis of early lesions of CXPA. This is applied to carcinomas with luminal or myoepithelial differentiation.     

Gastric form of alpha chain disease

A case of alpha chain disease, involving the stomach only, is reported in an Algerian man suffering from epigastric pains. Upper digestive tract fibreoptic endoscopy showed two antral ulcers and an ulcerative gastritis pattern, which promptly disappeared with cimetidine treatment. Antral biopsies at a distance from the ulcers, but not of the ulcer crater itself, disclosed a dense infiltration of antral lamina propria by mature or sometimes atypical plasma cells. On transmural surgical antral biopsy, the infiltrate spread to the superficial part of the submucosa. No other localisation of the disease was found in spite of multiple biopsies obtained by endoscopy, with a peroral capsule and during staging laparotomy. The alpha chain disease protein was absent from serum and urine, but found in the gastric juice and in the cytoplasma of the cellular infiltrate (alpha 1 subclass). A complete clinical, endoscopic, histological and immunological remission was observed after a six months' course of oral tetracycline.     

Surgical management of gallbladder sarcomatoid carcinoma

AIM： To study the behavior as well as optimal treatment of gallbladder sarcomatoid carcinoma, we reviewed the results of treatment of gallbladder sarcomatoid carcinoma from Chang Gung Memorial Hospital. METHODS： From 1987 to 2005, six patients were diagnosed with gallbladder sarcomatoid carcinoma and treated at our institution. Tumor staging was based on 2002 revised tumor-node-metastasis （TNM） staging for gall bladder cancer from the American Joint Committee on Cancer. The clinical presentation, laboratory data and preoperative workup were reviewed retrospectively. RESULTS： Five patients were female and one was male. The age ranged from 51 to 66 years （median, 58 years）. Surgical procedures included three curative resections, two palliative resections and one biopsy. There were two surgical complications （33.3%） and one case of surgical mortality （16.7%）. The follow- up time ranged from 30 d to 5 mo. The median survival was 2.5 mo. The prognosis was extremely poor, even after curative resection and postoperative chemotherapy. CONCLUSION： The prognosis of gallbladder sarcomatoid carcinoma was not dependent on TNM stage and was always dismal. The clinicopathological features were different from those of gall bladder cancer.     

Evolutionary genetics of the encapsulated strains of Haemophilus influenzae.

Genetic relationships among 2209 isolates of Haemophilus influenzae of polysaccharide capsule serotypes a, b, c, d, e, and f were determined by analyzing electrophoretically demonstrable allelic variation at 17 chromosomal enzyme loci. We distinguished 280 electrophoretic types (ETs), representing distinctive multilocus genotypes. Genetic diversity among ETs of isolates of the same serotype was, on average, only 67% of that in the total sample, and no ETs were shared among isolates of different serotypes. Cluster analysis of the ETs revealed 2 primary phylogenetic divisions at a genetic distance of 0.66 and 12 major lineages diverging from one another at distances greater than 0.42. In general, strains of different phylogenetic lines or groups of allied lineages have characteristic cap region restriction fragment length polymorphism patterns obtained by digestion of genomic DNA with EcoRI. Strains producing serotype c, e, and f capsules have no close relationships to those of other encapsulated strains. Lineages of both serotype a and b strains occur in each primary phylogenetic division, most probably as a result of the transfer of serotype-specific sequences of the cap region between clonal lineages. Serotype a strains allied in division I with a group of abundant serotype b clones and the serotype d strains apparently are more virulent than the serotype a strains in division II, which are related to serotype b and f strains that rarely cause invasive disease.     

Clinically unpredictable prognostic factors in the outcome of medullary thyroid cancer

Total thyroidectomy and central neck dissection are the procedures of choice in patients affected with medullary thyroid cancer. It is known that a medullary thyroid cancer with node metastases can be rarely cured, and therefore the utility of a modified radical neck dissection in the absence of suspicious node metastases still needs further evidence. The study aims to verify whether other epidemiological and pathological parameters could affect the prognosis of medullary thyroid cancer patients. We prospectively studied 70 medullary thyroid cancer patients consecutively operated on (from 2000 to 2004) at the same institution and analysed by the same pathologists. All patients underwent total thyroidectomy and central lymphadenectomy. In 27 cases, the ipsilateral (n=19) or bilateral (n=8) modified radical neck dissection was performed in the presence of suspicious lateral neck node metastases. After surgical treatment, basal and stimulated serum calcitonins (Cts) were measured in all patients. Follow-up ranged between 1 and 4 years. Patients were considered 'cured' when stimulated Ct was undetectable. Age, sex, tumour size, tumour capsule, multicentricity, nodes in the central neck and mean number of positive nodes were analysed in 'cured' and 'not-cured' patients. The presence of node metastases in the central compartment was significantly correlated with the outcome of the patients, being present in 9 and 72% of cured and not-cured patients respectively (P<0.000001). Tumour size was also significantly correlated with the outcome of the disease (P<0.00006). The presence of the tumour capsule correlated with better prognosis (P=0.0005) and absence of node metastases (P=0.0080). By multivariate analysis, the presence of node metastasis remained the most significant variable affecting the outcome of the disease (P=0.000014). Our results show that the outcome of encapsulated cancer is significantly better regardless of tumour size and node metastases. Although the early diagnosis and the extensive surgical treatment may favour the good outcome of medullary thyroid cancer, they do not always guarantee the definitive cure of the disease, being the capsular infiltration an independent bad prognostic factor.     

Usefulness of transbronchial and surgical biopsies for the management of interstitial lung disease

Interpretation of lung material can be very difficult in patients with interstitial lung disease. The pathologist must be particularly familiar with this type of situation since, unlike tumor diseases, the diagnosis is not purely histological and must always be established in correlation with the clinical and radiological presentation. In patients with suspected interstitial lung disease, the first diagnostic step is to perform a transbronchial biopsy or bronchoalveolar lavage. In many cases the two minimally invasive techniques can be combined to guide the diagnosis or establish confirmation. The indications for surgical biopsy can thus be limited to very exceptional situations. We recall here the requirement for rigorous handling of the endoscopic or surgical specimens and discuss the specific difficulties in interpreting the pathological material, focusing on the contribution of the pathological study to clinical surveillance of the disease course and its complications, particularly in treated patients. A close collaboration between clinicians and pathologists is essential for optimal diagnosis and management of interstitial lung disease.     

Clinical significance of cell differentiation in hepatocellular carcinoma

BACKGROUND/AIMS: Hepatocellular carcinoma is commonly found in Asian countries and prognosis still remains unsatisfactory due to recurrence after surgical tumor resection. METHODOLOGY: We try to demonstrate the recurrence and survival time in 99 surgical patients grading by tumor cellular differentiation from surgical specimen. RESULTS: The rates of well, moderate, and poor differentiation were encountered in 21 cases (21.2%), 61 cases (61.6%) and 17 cases (17.7%), respectively. Small tumor (< 3 cm) was found in only one (5.9%) in the poor differentiation group and 38.1% and 37.7% in the well and moderate differentiation groups. Capsular invasion was found in 13 (61.9%), 39 (63.9%) and 7 (41.1%) in the well, moderate and poor differentiation group, respectively. We found 41.9% (18/43) and 22.4% (13/58) to be tumor free in capsule invasion (-) and (+) after a period of 18.1 and 29.9 months, respectively. However, the recurrent time was 10.6 and 11.3 months, respectively with no significant difference (p > 0.05). Vascular invasion was more frequent in the poor differentiation group (76.5%) than the well (23.8%) and moderate (60.7%) differentiation groups (P < 0.05). We found 23.5% (4/17) and 35% (21/60) to be tumor free but the recurrence time was 6.5 and 14.1 months for the vascular invasion (-) and (+), respectively. The residual median survival times were 6.5 and 14 months after recurrence, respectively. The tumor recurrence rates were 52.7% (11/21), 52.4% (32/61), and 35.5% (6/17) and recurrence times were 11.7, 11.9, and 4.5 months for the well, moderate and poor differentiation group respectively totally. The recurrence time of young age group (< 39 years old) was shorter than the others and there was no patient of well differentiation less than 40 years old. The recurrence time was shorter in the poor differentiation group but there was no significant difference according to age group. The median survival times were 22.2, 22.9, and 9.5 months for each group, respectively. CONCLUSIONS: Differentiation of hepatocellular carcinoma cell had a clinical significance and was found to be positively correlated with the invasive proclivity. The median survival time was longer in both the well and moderate differentiation group, but not in the poor differentiation group. The clinical data revealed that the extended operations performed upon the patients with poor differentiation effected the recurrence time but not the survival time.     

Evaluation of dysplasia in gastrointestinal diseases

Dysplasia, or intraepithelial neoplasia, consists of noninvasive neoplastic cellular proliferation that may precede or accompany invasive neoplasia. Diagnosis is mainly based on histological criteria, which include cytological and structural alterations, since macroscopically identifiable lesions often do not occur. In all current classifications, dysplasia is divided in two categories, low- and high-grade, with the aim of attempting to evaluate risk and guide the therapeutic approach. The classification of the Vienna consensus aims to unity criteria and decrease interobserver variability in diagnosis. In the digestive tract, evaluation of epithelial dysplasia is especially important in four entities: Barrett's esophagus, chronic gastritis, inflammatory bowel disease, and colorectal adenomas. The criteria for diagnosis and dysplasia staging are the same in all these entities, but the therapeutic approach may vary according to the affected organ and the clinico-pathological context.     

RUNX3蛋白在人结直肠癌中的表达及其临床意义

背景:Runx3(runt相关转录因子3)基因是一种新发现的抑癌基因,近年研究发现Runx3异常表达与人类多种消化系肿瘤的发生密切相关。目的:研究人结直肠癌中RUNX3蛋白的表达,分析其表达与结直肠癌临床病理特征的关系。方法:以免疫组化方法检测90例结直肠癌患者的癌组织和癌旁组织中RUNX3蛋白的表达。结果:结直肠癌组织中RUNX3蛋白的阳性表达率(47.8%,43/90)显著低于癌旁结直肠黏膜组织(100%,P<0.05)。RUNX3蛋白的表达与结直肠癌患者的性别、年龄、肿瘤部位、大小和组织学类型无关(P>0.05),与肿瘤浸润深度、分化程度、Dukes分期和有无淋巴结转移有关(P<0.05),浸润越深、分化程度越低、Dukes分期越晚和有淋巴结转移的癌组织,RUNX3蛋白低表达越明显。结论:RUNX3蛋白的表达可能与结直肠癌的浸润、分化和转移相关,提示RUNX3蛋白表达下调可能对结直肠癌的发生、发展具有重要作用。     

肝癌动脉化疗栓塞效果的病理评价

目的研究肝细胞癌经动脉化疗栓塞治疗后癌肿的变化，探索提高疗效的方法。方法对动脉化疗栓塞治疗后行手术的３９例肝癌和１１例对照标本进行坏死程度与包膜、治疗次数、病理类型、分化、血管损伤及淋巴细胞浸润诸因素相关性的分析。结果完全坏死者６例，３０％＿９５％坏死者１４例，仅５％坏死及无坏死者１９例，１１例ＤＳＡ无坏死。癌肿坏死程度与肿癌分化、治疗次数、淋巴细胞浸润无关，而与病理类型、包膜、血管损伤有关。结论肝癌动脉化疗栓塞是中晚期肝癌目前唯一可取的治疗方法。对于有包膜的肝细胞癌，只要治疗能达到癌肿部位，即使一次治疗，也可收到明显的效果。对于如何使每例都达到彻底的癌肿坏死是值得进一步探讨的。     

超声内镜对壶腹癌及肝外胆管癌术前分期诊断

超声内镜对手术前Ｖａｔｅｒ＇ｓ壶腹癌及肝外胆管癌的原发病变范围、浸润深度、是否有区域淋巴结转移及远隔转移作出诊断及分期，将有助于选择最佳治疗方案及判断预后。对２８例Ｖａｔｅｒ＇ｓ壶腹癌及１８例肝外胆管癌于手术前进行了超声内镜检查，并按照国际ＴＮＭ分期方案进行了手术前分期。其中２２例Ｖａｔｅｒ＇ｓ壶腹癌及１８例肝外胆管癌进行了根治性切除及详细的病理组织学检查，有可能将超声内镜与病理诊断结果进行对照以检验超声内镜诊断的准确性。超声内镜判断Ｖａｔｅｒ＇ｓ壶腹癌及肝外胆管癌病变范围及浸润深度的准确性分别为８１．８％及７２．２％；判断其区域淋巴结转移的准确性分别为５９％及６１．６％。Ｖａｔｅｒ＇ｓ壶腹癌伴门静脉受侵的３例中有２例于术前超声内镜检查中获得了正确诊断，但３例肝转移均未能发现。     

Prognostic relevance of a histologic classification system applied in bone marrow biopsies from patients with multiple myeloma: A histopathological evaluation of biopsies from 153 untreated patients*

Abstract: A total of 153 diagnostic bone marrow biopsies from patients with advanced stages of multiple myeloma corresponding to stages II and III according to the Durie/Salmon classification were evaluated prior to any treatment in a prospective therapy trial of the German Myeloma Treatment Group. Histologic sections were analyzed according to a pre-defined system of criteria microscopically by 2 observers, determining three criteria: 1) grading by histopathology, regarding the cytologic differentiation of neoplastic cells and quantifying the percentage of plasmacytic, pleomorphic, and plasmablastic myeloma cells distributed within the sections; 2) the volume of infiltration; and 3) the pattern of neoplastic growth. Furthermore, four other criteria, namely hematopoiesis, fiber increase, osteomalacia, and micro-osteo-lesions, were evaluated. A cluster analysis using the three histological criteria revealed three groups of patients with significantly different survival times based on histological criteria only; the three criteria were mentioned above. It is concluded from these results that bone marrow biopsies, when evaluated histologically by grading and staging according to the three criteria, provide most valuable prognostic parameters in myeloma patients.