The overall metastatic rate in early esophageal adenocarcinoma: long-time follow-up of surgically treated patients.

The overall metastatic potential of surgically treated early esophageal adenocarcinoma has not been studied in detail. This paper therefore assessed lymph node metastases at surgery, loco regional and distant metastases, in order to assess the metastatic potential of early esophageal adenocarcinoma. Two hundred and seventeen patients (53 T1a, 164 T1b; median follow-ups 87 and 75 months, 187 males) diagnosed with early esophageal adenocarcinoma and treated with esophagectomy in our tertiary center's database between July 2000 and December 2015 were included. All metastatic events were retrospectively analyzed, their topographic distribution was assessed, and the overall metastatic rate was calculated. Lymph node metastases occurred in 39 patients (18%) and 29 (13.4%) developed recurrences. Lymph node metastases were absent in m1 and m2 tumors and rare in m3 (1/18), m4 (5/21), and sm1 (4/42), but more frequent in sm2 (11/44) and sm3 tumors (18/78). Locoregional recurrences were exceedingly rare in m3 (2/18), m4 (1/21), sm1 (1/42), and sm2 (2/44), but frequent in sm3 (12/78). In contrast, distant metastases were more frequent with 2/18 in m3, 1/21 in m4, 4/42 in sm1, 4/44 in sm2, and 13/78 in sm3. Overall metastatic rates of 11.9% in sm1 (submucosal layer divided into equal thirds), 27.3% in sm2, and 32.1% in sm3 tumors were calculated. This first report of the metastatic potential of early esophageal adenocarcinoma provides a meticulous assessment of the overall metastatic risk. Metastatic events pose a relevant risk in surgically treated patients with esophageal adenocarcinoma with distant metastases being more frequent than locoregional recurrences.

Early-stage adenocarcinoma of the esophagus with mid to deep submucosal invasion (pT1b sm2-3): the frequency of lymph-node metastasis depends on macroscopic and histological risk patterns.

The rate of lymph-node (LN) metastasis in early adenocarcinoma (EAC) of the esophagus with mid to deep submucosal invasion (pT1b sm2/3) has not yet been precisely defined. The aim of the this study was to evaluate the rate of LN metastasis in pT1b sm2/3 EAC depending on macroscopic and histological risk patterns to find out whether there may also be options for endoscopic therapy as in cancers limited to the mucosa and the upper third of the submucosa. A total of 1.718 pt with suspicion of EAC were referred for endoscopic treatment (ET) to the Dept. of Internal Medicine II at HSK Wiesbaden 1996-2010. In 230/1.718 pt, the suspicion (endoscopic ultrasound, EUS) or definitive diagnosis of pT1b EAC (ER/surgery) was made. Of these, 38 pt had sm2 lesions, and 69 sm3. Rate of LN metastasis was analyzed depending on risk patterns: histologically low-risk (hisLR): G1-2, L0, V0; histologically high-risk (hisHR): ≥1 criterion not fulfilled; macroscopically low-risk (macLR): gross tumor type I-II, tumor size ≤2 cm; macroscopically high-risk (macHR): ≥1 criterion not fulfilled; combined low-risk (combLR): hisLR+macLR; combined high-risk (combHR): at least 1 risk factor. LN rate was only evaluated in pt who had proven maximum invasion depth of sm2/sm3, and who in case of ET had a follow-up (FU) by EUS of at least 24 months. 23/38 pt with pT1b sm2 lesions and 39/69 pt with sm3 lesions fulfilled our inclusion criteria. In the pT1b sm2 group, rate of LN metastasis in the hisLR, hisHR, combLR, and combHR groups were 8.3% (1/12), 36.3% (4/11), 0% (0/5), and 27.8% (5/18). In the pT1b sm3 group, rate of LN metastasis in the hisLR, hisHR, combLR and combHR groups were 28.6% (2/7), 37.5% (12/32), 25% (1/4), and 37.1% (13/35). 30-day mortality of surgery was 1.7% (1/58 pt). In EAC with pT1b sm2/3 invasion, the frequency of LN metastasis depends on macroscopic and histological risk patterns. Surgery remains the standard treatment, because the rate of LN metastasis appears to be higher than the mortality risk of surgery. Whether a highly selected group of pT1b sm2 patients with a favourable risk pattern may be candidates for endoscopic therapy cannot be decided until the results of larger case volumes are available.

[Determination of tumor biological parameters in breast cancer: round robin testing for quality assurance]. / Bestimmung tumorbiologischer Parameter beim Mammakarzinom: Ringversuche zur Qualitätssicherung.

Round robin testing for quality assurance in the determination of the breast cancer biomarkers estrogen receptor (ER), progesterone receptor (PR) and epithelial growth factor receptor 2 (HER2) have been carried out in Germany for 13 years. As the first quality assurance trial worldwide tissue microarrays with 20 different breast cancer specimens were used. As a further innovation the challenges were split into a test part representing routine cases and a training part enriched with difficult borderline cases in order to uncover latent weaknesses in the participating laboratories. Certificates are issued based exclusively on the test part. Similar to NordiQC and UKNequas stained slides are assessed externally and the quality of staining and evaluation are considered separately. Since 2010 an additional internet-based trial without assessment of the staining quality is offered for ER and PR. Since the introduction of the round robin trials the numbers of participants (n = 200-250) and the success rates have steadily increased. The breast cancer quality assurance trial ranks first with regard to the number of participants in Germany. It could be demonstrated that regular participation in the round robin test leads to an improvement of staining results of ER, PR and HER2 and hence appears to be mandatory for maintaining quality standards. The use of fully automated immunohistochemical staining procedures has steadily increased and these are now used by approximately 50 % of participants.

[Tumor infiltrates suspicious of carcinoma in mediastinal lymph nodes]. / Karzinomverdächtige Tumorinfiltrate in mediastinalen Lymphknoten.

Myelosarcomas are, due to their rarity, a difficult differential diagnosis. Not infrequently, extensive immunohistochemical staining for characterization of the tumor is performed, if one does not directly think of myelosarcoma. In the present case, there was a positivity of the myeloid blasts for cytokeratin. This may complicate the discrimination of myelosarcoma from carcinoma, in particular small cell carcinoma, not only in the mediastinum, but also in the skin, e.g., Merkel cell carcinoma.

Cerebral metastases in metastatic breast cancer: disease-specific risk factors and survival.

BACKGROUND: Survival of patients suffering from cerebral metastases (CM) is limited. Identification of patients with a high risk for CM is warranted to adjust follow-up care and to evaluate preventive strategies. PATIENTS AND METHODS: Exploratory analysis of disease-specific parameter in patients with metastatic breast cancer (MBC) treated between 1998 and 2008 using cumulative incidences and Fine and Grays' multivariable regression analyses. RESULTS: After a median follow-up of 4.0 years, 66 patients (10.5%) developed CM. The estimated probability for CM was 5%, 12% and 15% at 1, 5 and 10 years; in contrast, the probability of death without CM was 21%, 61% and 76%, respectively. A small tumor size, ER status, ductal histology, lung and lymph node metastases, human epidermal growth factor receptor 2 positive (HER2+) tumors, younger age and M0 were associated with CM in univariate analyses, the latter three being risk factors in the multivariable model. Survival was shortened in patient developing CM (24.0 months) compared with patients with no CM (33.6 months) in the course of MBC. CONCLUSION: Young patients, primary with non-metastatic disease and HER2+ tumors, have a high risk to develop CM in MBC. Survival of patients developing CM in the course of MBC is impaired compared with patients without CM.

[Histopathological evaluation of the meniscus]. / Histopathologische Begutachtung des Meniskus.

Menisci fulfill many functions within the complex biomechanics of the knee joint. In the case of meniscus lesions, sparing arthroscopic resection and surgical refixation are the treatments of choice. In terms of diagnosis, this means in general that histopathologic diagnostics are carried out on detached meniscus fragments of between 5 mm and 2 cm in size. A good knowledge of physiologically possible cellular and fibrous histological meniscus damage, as opposed to nonphysiological change regarded as normal with respect to age, is essential for diagnostic meniscus evaluation. The clinician expects clear statements from the pathologist regarding the severity of previous or secondary degenerative meniscus damage, the age and type of traumatic tears, and an appraisal of the relationship between trauma and meniscus damage from an insurance point of view. Close cooperation between the clinician and the pathologist allows for a fast and unambiguous correlation of anamnesis, the clinical picture, and morphological reporting such that problematic insurance cases can be clarified quickly.

[Acetone compression. A fast, standardized method to investigate gastrointestinal lymph nodes]. / Acetonkompression. Schnelle, standardisierte Methode zur Untersuchung von Lymphknoten im Gastrointestinaltrakt.

Lymph node staging is the most important prognostic parameter in malignant gastrointestinal tumors. Manual dissection of adipose tissue is time-consuming and also depends on the experience of the individual examiner. By combining elution with acetone and mechanical compression using simple equipment it was possible to completely embed adipose tissue from 404 surgical specimens (colon 348, stomach 28, greater omentum 14, other location 14) without manual dissection. As a result of the procedure, the weight of the adipose tissue could be reduced by 90%-95%, making full histological examination possible. The colon specimens included an average of 43.8 lymph nodes (14-109) in 14 embedding cassettes (1-38) with a native fat weight of 234.7 g (42.8-820 g). The quality of histological staining, including immunohistochemical and molecular investigations, is of comparable quality to routine work-up. Elution with acetone enables the prompt, standardized and full histological work-up of adipose tissue without manual dissection. Moreover, additional costs are low. The number of lymph nodes required by medical associations was attained in all cases and often exceeded. This method was successfully used in other organs (greater omentum, breast).

Hypersensitivity pneumonitis associated with the use of temozolomide.

The aim of the present study was to investigate a case of hypersensitivity pneumonitis associated with the use of temozolomide in the treatment of gliosarcoma. A 54-yr-old female developed dyspnoea, cough and hypoxia after surgical resection for gliosarcoma and adjuvant radio- and chemotherapy with temozolomide. A high-resolution computed tomography scan of the thorax showed a bilateral ground-glass pattern. Bronchoscopy with bronchoalveolar lavage and lung biopsies was performed. Bronchoalveolar lavage demonstrated significant lymphocytic alveolitis and transbronchial lung biopsies revealed lymphocytic infiltration with foamy macrophages, consistent with hypersensitivity pneumonitis. There was no evidence of other causes, including infections. After withdrawing temozolomide and initiating prednisolone therapy, the patient had no further pulmonary symptoms. To the present authors' knowledge, this is the first definitively described case of temozolomide-associated hypersensitivity pneumonitis.

[New TNM classification of malignant lung tumors 2009 from a pathology perspective]. / Neue TNM-Klassifikation maligner Lungentumoren 2009 aus Sicht der Pathologie.

Based on the IASLC multicenter data collected worldwide on 81495 patients diagnosed or registered with lung cancer between 1990 and 2000, the T, N, and M descriptors were analyzed and recommendations for changes in the seventh edition of the TNM classification were proposed on the basis of differences in survival. This new TNM classification replaces the old UICC classification and the staging system according to C. Mountain 1997. The changes principally affect the T and M classifications. For the T component, tumor size was found to have prognostic relevance and its analysis led to recommendations to subclassify T1 into T1a and T1b, and T2 tumors into T2a and T2b and to reclassify T2 tumor>7 cm into T3 tumors. In the M category, M1 was recommended to be subclassified into M1a (contralateral lung nodules and pleural dissemination) and M1b (distant metastasis). There is no change in the N category. The proposed changes for the new stage grouping are to upstage T2b N0 M0 from stage IB to stage IIA and to downstage T2a N1 M0 from stage IIB to stage IIA and T4 N0-N1 M0 from stage IIIB to stage IIIA. The particulars of the new classification are discussed in the context of practice-relevant aspects from a pathology perspective view.

[The role of the pathologist in mammography screening]. / Die Rolle des Pathologen im Mammographie-Screening.

Within the framework of mammography screening programmes the expertise of the pathologist is embedded in an interdisciplinary diagnostic and therapeutic procedure. The quality of histopathological diagnosis not only depends on the expertise of the pathologist, but also requires skillful co-operation with the radiologist and the gynecologist who are both responsible for determining the medical indications for further radiographic and surgical tests and must ensure appropriate tissue samples are taken for non-palpable lesions. Bearing this process in mind it becomes clear that increased expertise in interventional tissue sampling leads to histological samples which are more representative. If the samples are not representative, their histological evaluation does not permit a conclusive statement on the origin of tissue abnormalities shown by mammography. At the mammography unit in Wiesbaden it was demonstrated that breast tissue punches almost always allow a precise histological diagnosis of tissue abnormalities and are at the same time appropriate for additional immunohistochemistry, such as for hormone receptors on carcinoma cells. Non-representative tissue samples are the exception.

[Sickle cell anemia in perinatal placental diagnostics]. / Sichelzellenanämien in der perinatalen Plazentadiagnostik.

Hereditary hemoglobinopathies should be considered as differential diagnosis when examining placental specimens for fetal growth retardation and spontaneous abortion. They can cause various macroscopic and microscopic changes in the placenta that are relevant for routine pathology examination. The importance of interdisciplinary co-operation between obstetrics and pathology to achieve optimum diagnostics and therapy planning is demonstrated using the case of a pregnant woman with heterozygous genotype and her child with homozygous genotype. Within this context, the influence of hemoglobinopathies on placental pathology and fetal development are summarized and exemplified.

[Histopathological meniscus diagnostic]. / Histopathologische Meniskusdiagnostik.

Menisci fulfill many functions within the complex biomechanics of the knee joint. In the case of meniscus lesions, sparing arthroscopic resections and operative refixation are the treatments of choice. With regard to diagnostics, this means that in general terms, the histopathologic diagnostics are carried out on detached meniscus fragments of between 5 mm and 2 cm in size. An experienced pathologist's knowledge of physiologically possible cellular and fibrous histological meniscus damage, as opposed to nonphysiological change regarded as normal with respect to age, is essential during a diagnostic meniscus evaluation. The clinician expects clear statements from the pathologist regarding the severity of previous or secondary degenerative meniscus damage, the age and type of traumatic tears, and appraisal of the relationship between trauma and meniscus damage from an insurance point of view. Close cooperation between the clinician and the pathologist allows for fast and unambiguous correlation of anamnesis, the clinical picture, and morphological reporting so that cases involving insurance problems - which are numerous, often long-term, and often unsatisfactory - can be clarified quickly.

[Interlaboratory trials for quality assurance of breast cancer biomarkers in Germany]. / Ringversuche zum Nachweis von therapeutischen Zielmolekülen beim Mammakarzinom in Deutschland.

In the age of personalized medicine, and in addition to typing and grading, breast cancer pathologists are now also involved in determining biomarkers such as steroid hormone receptors and Her-2, which are of the utmost importance in adjuvant therapy. In order to assure quality of these biomarker assays, external proficiency testing has been implemented in Germany. Since 2002 trials have been conducted annually, with up to 180 participating laboratories. More than 85% of all participants achieved good results in clearly negative and positive cases seen in daily practice. If at all, discordant results were observed in the rarer low steroid-hormone receptor expressing tumors and Her-2 borderline cases (2+). Regular participation in interlaboratory testing leads to significantly improved immunohistochemical results, particularly in these problematic cases. Tissue microarrays (TMA) with 20-24 different breast cancer samples including cell lines meant that a huge number of pathologists were challenged with identical samples, providing the prerequisite for comparability. Participation is recommended for pathology departments involved in the service for breast units. The organizational frame work of the trials is described here. The confidence of cooperating disciplines in breast cancer biomarkers assessed by pathologists will be fostered by external proficiency testing as presented here.

[Amiodarone-induced pneumonitis. Lethal complication in a patient after thoracic surgery]. / Amiodaroninduzierte Pneumonitis. Letale Komplikation bei einem thoraxchirurgischen Patienten.

The case of a 69-year-old patient is reported with non-small cell lung cancer who underwent lobectomy with sleeve resection and postoperatively developed intermittent atrial tachyarrhythmia. The patient was treated with a beta-blocker and the class III antiarrhythmic drug amiodarone, which resulted in normal frequency sinus rhythm. After pharmacological saturation with amiodarone, fibrosis of the lungs developed with subsequent respiratory insufficiency. Despite maximum intensive care therapy the patient died 9 weeks after surgery of hypoxemia-related multiple organ dysfunction syndrome. Based on this case amiodarone-related pneumonitis will be discussed, which due to a lack of pathognomonic symptoms is often difficult to diagnose and for which there are few treatment options available. The differential diagnoses of pneumonitis will also be discussed.

[Thoracic inflammatory pseudotumors : A rare differential diagnosis]. / Thorakale inflammatorische Pseudotumoren : Eine seltene Differenzialdiagnose.

BACKGROUND: Inflammatory pseudotumors are a rare and in the main benign tumor entity but infiltrative growth, recurrence and metastases are described. Generally, a complete resection is needed to exclude lung cancer. This study analyzed our data and experiences with this rare tumor entity. MATERIAL AND METHODS: We performed a retrospective study of all our patients who had been operated on between 2002 and 2016 in our institution for an inflammatory pseudotumor of the lungs. The extent of resection, morbidity, mortality and long-term results were analyzed. RESULTS: Altogether, in this period 13 patients were operatively treated (5 women and 8 men). The median age was 52 years (range 34-74 years). A reoperation was carried out in one patient for recurrence after enucleation of the tumor in another hospital. In no case could lung cancer be excluded prior to complete resection. In total, 11 pulmonary, 1 tracheal and 1 chest wall pseudotumor could be resected by thoracotomy (9×) and thoracoscopy (3×) and 1 by ventral chest wall resection. In eight patients the resections were performed by standard resection (wedge resection or anatomic resection) and five times by extended resection. In all cases a R0 resection was achieved. Due to one case of postoperative pneumonia the morbidity and mortality rates were 7.7% and 0%, respectively. CONCLUSION: The differential diagnosis between inflammatory pseudotumors and lung cancer cannot be definitely made preoperatively. For an exact diagnosis by the pathologist a complete histological preparation is needed. Due to infiltrative growth and recurrence, extended resection can be necessary for a R0 resection. This can be achieved with low morbidity and mortality. Important is an en bloc R0 resection, which is associated with good long-term results.

Quality assurance trials for Ki67 assessment in pathology.

Ki67 is a broadly used proliferation marker in surgical pathology with an obvious need for standardization to improve reproducibility of assessment. Here, we present results of the so far only existing round robin tests on Ki67, organized annually in Germany, Austria, and Switzerland from 2010 to 2015 with up to 160 participating laboratories (QuIP). In each quality assessment trial, eight probes from each breast cancer, neuroendocrine tumor, and malignant lymphoma were compiled on a tissue microarray (TMA). TMAs were stained in the participants' laboratories with antibodies and procedures also applied in their daily routine. Participating pathologists were expected to assign Ki67 values to one of four different categories for each tumor type. All local stainings and evaluations were reassessed by the organizing panel and compared to a preset standard. On average, 95% of participants reached the benchmark of over 80% concordance rates with the Ki67 category pre-established by the panel. Automatization and type of antibody did not affect the success rate. Concordance rates differed between tumor entities being highest in each tumor type with either very high or very low labeling indices. Lower rates were seen for intermediate Ki67 levels. Staining quality improved during the observation period as did inter-observer concordance with 85% of participants achieving excellent agreement (kappa > 0.8) in the first year and over 95% in 2015. In conclusion, regular external quality assurance trials have been established as a tool to improve the reproducibility and reliability of the prognostic and predictive proliferation marker Ki67.