[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.

[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.

[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.

[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.

[Fever and nonspecific pulmonary lesions--a rare differential diagnosis]. / Fieber und unklare pulmonale Infiltrate--eine seltene Differenzialdiagnose.

HISTORY AND ADMISSION FINDINGS: A 70-year-old woman presented with rapidly increasing weakness, night sweats, progressive dyspnea and daily fever up to 39 C. 30 years before early stage breast cancer had successfully been treated by resection. INVESTIGATIONS: Blood tests revealed moderate normocytic anemia and a considerable elevation of the serum level of lactate dehydrogenase (LDH). The differential blood count was normal. Chest radiography showed interstitial infiltrates. Computed tomography revealed reticular shadows and ground-glass opacities which on histological examination were attributed to intravascular lymphoma (IVL) of B cell lineage. TREATMENT AND COURSE: Treatment with eight cycles of the R-CHOP 14 regimen (rituximab, cyclophophamide, doxorubicine, vincristine, prednisone; interval: 14 days) resulted in complete remission with rapid resolution of constitutional symptoms. 7 months later the IVL relapsed, again with fever and an elevation of the LDH level. Bone marrow biopsy revealed intravascular infiltration by lymphoma cells. Salvage treatment with six courses of a methotrexate-containing protocol led to a second complete remission. CONCLUSION: Nonspecific constitutional symptoms, a large variety of potential clinical presentations and the infrequency of the disease render the ante mortem diagnosis of an intravascular lymphoma difficult. Treatment follows the same principles as in nodal aggressive non-Hodgkin's lymphomas.

Dualism of mixed chimerism between hematopoiesis and stroma in chronic idiopathic myelofibrosis after allogeneic stem cell transplantation.

Scant knowledge exists concerning lineage-restricted mixed chimerism (mCh) after allogeneic peripheral blood stem cell transplantation (PSCT) in patients with chronic idiopathic myelofibrosis (CIMF). Following a sex-mismatched PSCT, a combined immunopheno- and genotyping by fluorescence in-situ hybridization (FISH) was performed on sequential bone marrow (BM) biopsies at standardized intervals. Results were compared with PCR analysis of corresponding peripheral blood samples in five patients. According to FISH, pretransplant specimens revealed a gender congruence of more than 99%, while in the first three months the total BM exhibited a persistent fraction of host cells (30% to 40%) with a tendency to decline after about one year. It is noteworthy that the majority of endothelial cells maintained a recipient origin, whereas CD34+ progenitors and especially CD61+ megakaryocytes exhibited only very few host-derived cells. In keeping with the prevalence of donor cells in the hematopoietic compartment, PCR analysis of peripheral blood cells displayed a non-significant degree of mCh. In conclusion, according to FISH and PCR analysis, successful PSCT in CIMF results in an almost complete chimeric (donor-derived) state of the hematopoietic cell population. The non-transplantable stromal compartment includes the vascular endothelium with a predominance of recipient cells. The minimal mCh of this population implies probably a donor-derived origin (endothelial progenitor cells).

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.

[Two cystic retroperitoneal lesions mimicking adrenal cysts]. / Retroperitoneale Zysten, die Nebennierenzysten imitieren können.

Adrenal cysts are uncommon lesions and most of them are found incidentally during abdominal imaging. We report on two benign extraadrenal lesions mimicking adrenal tumors in abdominal imaging. The histopathological investigation of the lesions revealed a foregut duplication cyst of the lesser gastric curvature and an epithelial inclusion cyst (epidermoid cyst) in an intrapancreatic accessory spleen respectively.

[Squamous cell carcinoma of the external ear. A carcinoma of old age which requires individualized therapy planning]. / Das Plattenepithelkarzinom der Ohrmuschel. Ein Alterskarzinom erfordert eine individualisierte Therapieplanung.

METHODS: Data for all patients with ear malignancies being operated in our department between August 1988 and March 2001 were retrospectively analyzed for tumor localisation, stage, biometric data, anesthesiological risk factors, therapy and recurrence of the disease. RESULTS: Thirty of 79 patients (29 male, one female; average age 77.2 years, range 54-99 years) with cutaneous malignancies of the external ear were diagnosed as SCC ( n=32 SCC). A total of 17 SCC were smaller than 2 cm, 12 were between 2-5 cm, and three were larger than 5 cm. Only two patients had regional nodal disease, none had distant metastases. The anesthesiological risk was estimated according to the recommendations of the American Society of Anesthesiologists (ASA); 16/30 patients were classified as group 3 or 4, having severe general disease with a decrease in vitality or even vital risks. A total of 24 SSC were primarily operated under local anesthesia. Depending on histology, localisation and size of the SCC local excision, partial or total removal of the auricle was performed. In the remaining 8/32 cases, the primary intervention was performed under general anesthesia, mostly in combination with an ipsilateral neck dissection and a superficial parotidectomy. In 8/32 cases, the SCC had to be re-operated after primary R1 resection. Altogether, eight patients received radiotherapy. In 5/32 cases there was a recurrence of the disease. The average follow-up period of the 13 patients who are still alive is 50 months (17-113). One patient died as a result of the metastasized SCC and 16 patients died due to other diseases. DISCUSSION: Considering the high age and the age-associated general diseases of the patients with SCC of the auricle, differentiation between a radical concept of therapy and its risks and possible therapy-related damage is important. Therefore, individual concepts such as partial removal of the pinna without neck dissection and parotidectomy for the N(0) stage are justified if relevant anesthesiological risk factors have to be taken into account.

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.

[Lymphadenopathy in the groin. Unusual etiology in a 65-year-old patient]. / Lymphknotenschwellung in der Leiste. Ungewöhnliche Ursache bei einer 65-jährigen Patientin.

A 65 year old female patient was admitted to our hospital with unspecific symptoms and a lump in the right groin which raised suspicion of a malignant lymphoma. Histologically a follicular dendritic reticular cell tumor was found. Because there are aggressive forms of this tumor and no established standard therapy, we decided to treat her with surgery followed by a combined radio- and chemotherapy. Despite this treatment 16 months after the first diagnosis a relapse occurred with a metastasis of the follicular dendritic cell tumor in the lung. The metastasis was resected surgically. The optimal management of this kind of tumor is not known.

[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.

[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.

Increased expression of metallothionein in inflammatory bowel disease.

OBJECTIVE: Metallothioneins (MT) are cytoprotective against the damaging effects of oxygen-derived free radicals. Therefore MT may be involved in defence mechanisms to counter Crohn's disease (CD) and ulcerative colitis (UC). MATERIALS: 107 routinely processed tissue samples from 22 patients with CD and 48 patients with UC were tested with the monoclonal anti-MT antibody E9. METHODS: Immunohistochemistry was used to assess MT staining in a semiquantitative manner. Chi-square test was used for statistical analysis. RESULTS: MT overexpression was found in the fibroblasts of all ulcerative and/or fissural lesions in UC and CD. MT overexpression in intestinal epithelial cells of 40% of UC and CD lesions correlated significantly with the grade of inflammation. CONCLUSIONS: MT-immunoreactivity in fibroblasts supports a protective role for MT in inflammatory bowel disease. It remains unclear whether MT overexpression in epithelial cells is also important in this protection.

Haemangiopericytoma of the nasal cavity.

Haemangiopericytomas (HPC) are rare vascular tumours originating from a pericytes, a term coined by Zimmermann to refer to the main location of this cell line in the pericapillary connective tissue. HPC may arise in any part of the body. We report a 29-year-old man with a histologically proven nasal haemangiopericytoma-like tumour. The lesion was embolised through the ophthalmic artery before it was removed surgically. The main symptoms of nasal HPC are epistaxis and obstruction of the nose. Malignant and benign clinical courses have been described. Local recurrence and metastases may be observed years after initial diagnosis.

Keyhole limpet hemocyanin for carcinoma in situ of the bladder: a long-term follow-up study.

OBJECTIVE: Keyhole limpet hemocyanin (KLH) is a nonspecific immunomodulator, demonstrated to be clinically effective in superficial bladder cancer. The present study investigated the clinical efficacy of intravesical KLH in patients with carcinoma in situ (CIS) with a long-term follow-up. METHODS: Thirteen patients with CIS grade III were treated with intravesical instillations of KLH, 20 mg for 6 weeks, then monthly for 1 year and bimonthly for 2 subsequent years. Patients not responding to 2 courses of KLH were treated with bacillus Calmete-Guérin (BCG, 81 mg Connaught strain). RESULTS: The follow-up period ranged from 12 to 84 months. Two patients were free of tumor after KLH instillations with a follow-up of 66 and 82 months, respectively. All patients who did not respond to the primary KLH course, but to the 'rescue' instillation of BCG, experienced recurrences after 42, 48, 56 and 60 months after the first KLH instillation treatment. Three patients with recurrent CIS and who were not cystectomized had recurrences after prolonged remission (4-5 years). Patients progressing despite KLH and BCG instillations underwent cystectomy. CONCLUSIONS: KLH demonstrates efficacy and induces long- term remissions against CIS in a limited number of cases. In the present study, most patients with CIS progressed over time whatever the substance instilled, whether KLH or BCG. CIS remains a very aggressive neoplasm requiring a lifelong follow-up. Further studies are necessary to define the precise role of KLH in patients with CIS.