[Retinoblastoma and retinocytoma (retinoma)]. / Retinoblastom und Retinozytom (Retinom).

Retinoblastomas are extremely rare withabout half of the cases being hereditary eye neoplasms in young children. They show highly proliferative, CRX-positive undifferentiated tumour cells (occasionally forming rosettes). Staging is performed according to the pTNM classification and the International Retinoblastoma Staging System (IRSS). The diagnostic basis for systemic administration of chemotherapy and/or radiation is postlaminar optic nerve invasion, massive choroidal tumour infiltration, scleral invasion or even extraocular invasion. In cases that are difficult to diagnose, immunohistochemical stains (CRX and Ki67) may be very helpful. Retinocytomas (retinomas) completely lack undifferentiated tumour cell areas, show an exclusive photoreceptor differentiation and an exceptionally low Ki67 index.

[Intraocular metastases]. / Intraokulare Metastasen.

Metastatic cancer represents the most common form of intraocular malignancy. Due to its abundant vascular supply the choroid is the most common ocular site for intraocular metastatic disease (approximately 90%). Less than 10% of intraocular metastases are located in the iris and/or ciliary body, whereas the retina and vitreous are rarely affected. Most intraocular metastases are carcinomas; the majority of metastases originate from breast cancer in females and lung cancer in males. However, virtually every primary malignancy has been described to metastasize to intraocular structures. In this review we address the pathology and clinical features of intraocular metastases, noninvasive and invasive diagnostic procedures, as well as the pathological work-up of cytological and histological specimens obtained either by fine needle aspiration biopsy or special biopsy forceps.

[Heterotopic gastric mucosa of the rectum. Case report with literature review]. / Rektale Magenschleimhautheterotopie. Ein Fallbericht in Zusammenschau mit der Literatur.

Heterotopic gastric mucosa is a rare finding in the rectum. Apart from two other hypotheses, a misdifferentiation of entodermal stem cells is the most widely accepted aetiopathogenetic assumption today. Due to acid secretion, the lesions predominantly manifest with hematochezia. Therapeutic options include medicinal therapy and particularly (endoscopic) removal. From the pathologist's point of view a careful evaluation is required also in terms of basically possible dysplastic or malignant changes.

[TTF-1 (8G7G3/1) positive colon adenocarcinoma: diagnostic implications]. / TTF-1- (Klon 8G7G3/1) positives Kolonkarzinom: Diagnostische Implikationen.

Immunohistochemical evaluation of primary and secondary (adeno-) carcinomas of the lung often includes utilisation of two different clones (8G7G3/1 or SPT24) of TTF-1 (thyroid transcription factor 1) antibodies. In a subgroup of adenocarcinomas with a primary site other than the lung a positive reaction of clone SPT24 and also of clone 8G7G3/1 is described. We report on a patient with TTF-1 (clone 8G7G3/1) positive adenocarcinoma of the colon with metastases to the eye and lung and discuss TTF-1 based diagnostic considerations.

[Impressive picture of a melanosis coli after chronic anthraquinone laxative use--is there an increased risk for colorectal cancer?].

We report the case of a 74-year-old female with an extreme picture of melanosis coli of the whole colon after chronic use of anthraquinone laxatives for the treatment of constipation over many decades. Endoscopic work-up revealed an impressive deep black pigmentation of the whole colon mucosa which could be verified by histopathology as a widespread lipofuscin granulation. In addition, various adenomas but no colorectal carcinoma could be detected. The term melanosis coli describes a brown or black pigmentation of the colonic mucosa. Induction of melanosis coli by anthraquinone laxatives and their derivatives can be regarded as verified. The question if melanosis coli predisposes for colorectal neoplasia is discussed controversially. Based on the current literature, an association of melanosis coli between colorectal adenomas, but not colorectal carcinomas, is under discussion but the mechanisms to effect the development of colorectal neoplasia are not completely understood. Considering our case and the current scientific backround, we conclude that due to pharmaceutical side effects of anthraquinone derivatives such as electrolytic shift and water loss in addition to the risk of developing melanosis coli, anthraquinone laxatives should not be used for long-term therapy of constipation.

Dynamics of bone marrow changes in patients with chronic idiopathic myelofibrosis following allogeneic stem cell transplantation.

Scant knowledge exists about the dynamics of fibro-osteosclerotic bone marrow (BM) lesions and regeneration of hematopoiesis following allogeneic peripheral stem cell transplantation (SCT) in chronic idiopathic myelofibrosis. Therefore, an immunohistochemical and morphometric study was performed on BM biopsies in 20 patients before and at standardized intervals (days 30 through 384) following SCT. In responding patients, a total regression of the pretransplant increased fibrosis was completed in the posttransplant period after about six months, while the extent of osteosclerosis did not change significantly during observation time. The quantity of CD61+ megakaryocytes including precursors was strikingly variable after SCT and, by using planimetric methods, atypical microforms exhibiting a dysplastic aspect could be demonstrated. These anomalies may be responsible for posttransplant thrombocytopenia. CD34+ progenitor cells were increased before transplantation, however, their number declined rapidly to normal values in responding patients. Nucleated erythroid precursors revealed a decreased amount before and after SCT accounting for anemia. Large clusters of this cell lineage indicated an initial hematopoietic reconstitution comparable with the expansion of the neutrophil granulopoiesis. Proliferative activity and apoptosis showed an increase until one year after SCT that implied a still regenerating hematopoiesis in keeping with an enhanced cell turnover.

ETV6-NTRK3 gene fusion in a secretory carcinoma of the breast of a male-to-female transsexual.

Secretory carcinomas of the breast were first described as "juvenile carcinoma" by McDivitt and Stewart in a cohort of children. This term has been replaced by the term "secretory breast carcinoma", because the entity can occur at any time of life. Carcinoma of the male breast is uncommon and accounts for approximately 1% of all cancers in men. Recently, it has been reported that human secretory breast carcinoma expresses the ETV6-NTRK3 gene fusion that was previously cloned in pediatric mesenchymal cancers. We present the case of a 46-year-old male-to-female transsexual in whom a secretory breast carcinoma was an incidental finding. As confirmation of the histopathological diagnosis we detected the novel ETV6-NTRK3 gene fusion in this tumor.

Regeneration of heart muscle tissue: quantification of chimeric cardiomyocytes and endothelial cells following transplantation.

Persuasive evidence has been recently provided that adult bone marrow (BM) cells exert greater plasticity than previously assumed. This review is focused on the quantification of mixed chimerism (mCh) in the hearts (cardiomyocytes and endothelial cells) of patients after orthotopic heart to heart transplantation (HHT) in comparison to full (unmanipulated) allogeneic BM and peripheral blood stem cell (PBSC) transplants. Following a sex-mismatched transplantation constellation heart muscle tissue obtained at autopsy was examined. Evaluation of mCh was most often performed by immunophenotyping combined with fluorescence in-situ hybridization (FISH) applying x- and y-chromosome-specific DNA probes. When comparing our data with the results of former studies that were regularly based on the detection of the y-chromosome alone, the quantity of chimeric cardiomyocytes after HHT ranged from 0% to 9%. On the other hand, after full BM transplantats (chimeric) cardiomyocytes of donor-type origin appeared at an incidence between 0.23% to 6.4%. These disturbing inconsistencies were assumed to be related to methodology: the restriction to the y-chromosome, disregard of the plane of section (detection sensitivity ranging between 35% and 67%) and state of tissue preservation (cadaver hearts). Therefore, when strictly applying dual color FISH and limiting the recognition of chimeric cardiomyocytes and endothelial cells to the presence of two distinctive signals detection sensitivity was significantly enhanced. Contrasting a total congruence with the genotyping in control specimens of normal cadaver hearts, a striking disparity in the extent of mCh was found depending on the different modes of transplantation. After allografting with PBSC a considerably low incidence (1.6%) of chimeric cardiomyocytes was determined contrasting with 5.3% of donor-derived cells after full BM transplants. Following HHT host-type endothelial cells (16.2%) of the intramural and subepicardial vessel walls were more often encountered than following BM and PBSC allografting. These findings are in keeping with the assumption of a sprouting and migration of vascular structures into the donor heart from the site of surgical aligment and injury between retained host and donor atrial walls. When considering the other methods of transplantation (BM, PBSC) the data on chimeric endothelial cells support the hypothesis of a common hemangioblast. Concerning the cardiomyocytes it seems most reasonable to assume that primitive mesenchymal stem cells of the BM play a pivotal role in the development of mCh. This phenomenon is more extensively expressed than previously expected and may be related to an enforced repair of the damaged myocardium during the post-transplant period as the sequel of myeloablative (cardiotoxic) conditioning.

Effect of keyhole limpet hemocyanin (KLH) and bacillus Calmette-Guérin (BCG) instillation on carcinoma in situ of the urinary bladder.

Patients with histologically verified carcinoma in situ (CIS) of the urinary bladder (13 primary and 8 secondary CIS) were treated with intravesical instillations of Keyhole Limpet Hemocyanin (KLH) (20 mg KLH weekly for 6 weeks, then monthly for 1 year or bimonthly for 2 subsequent years. Patients, non-responding to 2 courses of KLH were then treated with regular Bacillus Calmette-Guerin instillations (120 mg BCG-Connaught strain). The follow-up period ranged from 10 to 54 months (mean 23.5 months). 7 patients (33%) were free of tumor after the first therapeutical KLH course and 4 patients (19%) presented a complete-remission after the second KLH course (total primary response: 52%). 5 patients (24%) remained free of tumor during the established follow-up period (mean 31.7 months) and no evidence of further tumor progression occurred in patients after two courses of KLH treatment. However, 2 patients (9.5%) had to be cystectomized after KLH instillations because of progressive disease or tumor recurrence. 8 patients (38%) had to be radically cystectomized because of CIS persistence or progression after KLH and subsequent BCG treatment. Altogether 9 patients (42.8%) presented long-term remissions, with a mean duration of 31.3 months. Instillations of KLH did not induce major side effects; however, instillations of BCG caused severe dysuria in 60% and fever in 40% of patients.

Adenocarcinoma of the colon with syncytiotrophoblastic differentiation: differential diagnosis and implications.

A case of adenocarcinoma of the colon is reported, whose metastases exhibited a syncytiotrophoblastic differentiation that gradually increased with advancing distance from the primary. Immunohistochemically, syncytiotrophoblastic giant cells with strong positivity for beta-HCG could be demonstrated within the metastatic tissue. Also, there was beta-HCG positivity in a fraction of the atypical epithelial elements of the primary. The case is discussed with respect to the differential diagnosis, and the cause of the syncytiotrophoblastic differentiation is attributed to the phenomenon of genetic instability. The case shows that by virtue of genetic instability totally new differentiations may be elaborated, so that the phenotypical appearance of a given tumor does not necessarily allow conclusions as to its tissue of origin. Thus, observations such as the one presented here clearly indicate that the histogenetic principle of tumor classifications by far does not apply to all cancers and that, therefore, its value and validity are considerably limited.

CD30 differential staining is useful in classifying lymphomas intermediate between Hodgkin's disease and anaplastic large cell (Ki1) lymphoma.

AIMS AND BACKGROUND: The authors analyzed the BerH2 reactivity patterns of the tumor cells in 23 Hodgkin's lymphomas (HD), in 13 CD30+ anaplastic large cell (Ki1) lymphomas (ALCL), in two HD with transition to secondary CD30+ ALCL, and in six additional lymphomas intermediate between HD and ALCL. METHODS: Paraffin blocks of formalin-fixed biopsies were immunostained. Immunostaining was modified by pronase digestion and by microwave assistance. RESULTS: Hodgkin-Reed-Sternberg (HRS) cells of all 23 Hodgkin's lymphomas were reactive for BerH2, but the reactivity patterns differed: after pronase digestion, HRS cells of 17/23 Hodgkin's lymphomas showed exclusively or at least predominantly cytoplasmic BerH2 reactivity, whereas only four Hodgkin's lymphomas presented with prominent membrane-bound positivity. Microwave processing in 16/23 Hodgkin's lymphomas induced membrane-bound BerH2 positivity in the HRS cells; a minority of five cases retained the distinct cytoplasmic pattern. In contrast, 10/13 ALCLs were characterized by membranous reactions, independent of whether pronase or microwave pretreatment had been applied. The CD30+ ALCLs secondary to HD also showed a tendency towards membranous positivity more than did the antecedent Hodgkin's lymphomas. In the HD/ALCL borderline group, 3/6 cases revealed cytoplasmic BerH2 patterns after pronase digestion and thus were more closely related to HD, whereas 2/6 cases reacted with membranous positivity as did the genuine ALCLs of our series. CONCLUSIONS: We conclude from these findings that the above modifications in CD30 immunostaining can be helpful in the characterization of lymphomas that constitute a continuous histomorphological as well as phenotypical spectrum between HD and ALCL.

Well-differentiated (oncocytoid) neuroendocrine carcinoma of the larynx with multiple skin metastases: a brief report.

A 63-year-old woman presented with a history of increasing dysphagia of about two weeks duration. Laryngoscopy revealed a nonulcerated supraglottic epitheliomatous lesion that morphologically appeared well-differentiated and distinctly oncocytoid. Although the tumour lacked any criteria for malignancy such as cellular atypia, pleomorphism or necroses, it recurred twice after primary surgery and later gave rise to multiple painful skin metastases. The diagnosis of an oncocytoid differentiated neuroendocrine carcinoma of the larynx (laryngeal carcinoid) was made. Misinterpretation of laryngeal carcinoids is common, but can be avoided if one is familiar with this rare variant of laryngeal neoplasms.

[Endoscopic excision of extra-adrenal pheochromocytomas (paragangliomas)]. / Die endoskopische Exstirpation extraadrenaler Phäochromocytome (Paragangliome).

We describe the successful endoscopic removal of six extra-adrenal pheochromocytomas in three patients. One neoplasia was located retrocavally, two between the aorta and vena cava, two by the para-aortal, and one by the parailiacal. The tumors were removed by the posterior retroperitoneoscopic or by the anterior laparoscopic approach, respectively. The intraoperative and postoperative courses were uneventful.

[A bone-destroying tumor of the maxilla. Reparative giant cell granuloma or brown tumor?] / Knochendestruierender Tumor der Kieferhöhle : Reparatives Riesenzellgranulom oder brauner Tumor?

Brown tumors are focal bone lesions caused by an increased osteoclastic activity and fibroblastic proliferation within a primary or more rarely secondary hyperparathyroidism. They are named after their typical brown hemorrhagic stroma with its also typical giant cell formations.We report the case of a 31-year-old pregnant patient with a rapidly growing tumor of her left maxilla whose first symptoms during pregnancy mimicked chronic sinusitis.After swelling of the cheek, diplopia, and recurrent epistaxis appeared, she was referred to our Department for further diagnostics.After CT scan, biopsy was performed under the presumption of a malignant process with the surprising histological result of a reparative giant cell granuloma. At the same time, hyperthyroidism and nodular goiter were diagnosed and further endocrinological examinations were planned.Not until a parathyroid adenoma was diagnosed after urgent operation of the maxillary process (loose molar teeth and displacement of the left bulbus) could the tumor be interpreted and detected within this context of primary hyperparathyroidism as a brown tumor.The brown tumor should be taken into consideration as a rare differential diagnosis of a bone-destroying process of the facial bones.We discuss the clinical signs, diagnostics, and therapy for this case as well as the relevant literature. The reparative giant cell granuloma represents an important differential diagnosis and cannot be distinguished from a brown tumor by histological examination or radiological findings without complete information about the clinical signs and the endocrinological status of the patient.

[Detection of endometriosis during cesarean section for HELLP syndrome in the 32nd week of pregnancy]. / Erkennung einer Endometriose bei Sectio caesarea wegen HELLP-Syndrom in der 32. Schwangerschaftswoche.

The rare case of a decidualized endometriosis of the appendix vermiformis is reported in a woman who developed HELLP syndrome during the 32nd week of a twin pregnancy. Cesarean section and simultaneous appendectomy were performed. An inspection of the appendix should always be carried out if an endometriosis-associated anamnesis is known. No pathophysiological correlations between the HELLP syndrome and the endometriosis of the appendix vermiformis could be found.

[Value of transretinal tumor biopsy as diagnostic and predictive instrument]. / Stellenwert der transretinalen Tumorbiopsie als diagnostisches und prädiktives Instrument.

Transretinal biopsy of intraocular tumors plays a decisive role as a diagnostic tool in ocular oncology. A biopsy is indicated to confirm a clinical diagnosis before treatment and allows identification of high risk melanomas of the uvea with a high potential of metastasis by molecular genetic evaluation of the specimen. This review will focus on the various biopsy techniques and indications for this method.