[Eosinophilic Granulomatosis with Polyangiitis with Pulmonary and Cardiac Involvement]. / Eosinophile Granulomatose mit Polyangiitis mit pulmonaler und kardialer Beteiligung.

A 62-year-old patient with bronchial asthma and chronic rhinosinusitis underwent inguinal hernia surgery. After the operation, sudden circulatory arrest occurred, requiring cardiopulmonary resuscitation. Coronary angiography revealed a 99 % proximal stenosis of right coronary artery (RCA) with unsuspicious and smooth coronary vessel walls. In the further course, several similar events occurred, but without pathological findings in the coronary angiography. Initially, echocardiography showed slightly reduced left ventricular ejection fraction of 45 %. Chest radiography revealed bilateral pulmonary infiltrates, and white blood cell count showed severe eosinophilia (37 %). Serological antibody testing including ANA, ENA and c-/p-ANCA was negative. Myeloproliferative pathologies were excluded by bone marrow puncture. The patient suffered from emerging dyspnea, weakness, and ongoing weight loss. A methylprednisolone pulse of 250 mg/d for 3 days remained without significant effect, so that the patient was eventually referred to our university hospital due to ongoing clinical deterioration. On admission, the patient suffered from weakness, progressive muscular atrophy, and dyspnea on exertion. Physical examination revealed a right-sided peroneal paralysis. Bronchial lavage detected severe eosinophil alveolitis (37 %), and laboratory findings showed elevated cardiac enzymes and NT-proBNP (Troponin-T > 700 ng/l, NT-proBNP > 10.000 ng/l). Echocardiography revealed a dramatic deterioration of cardiac function (LVEF 16 %). Interdisciplinary discussion between pulmonologists and cardiologists lead to the diagnosis of ANCA-negative eosinophilic granulomatosis with polyangiitis (EGPA) with pulmonary and cardiac involvement. Initiation of immunosuppressive therapy with methylprednisolone 1000 mg/d for 3 days followed by cyclophosphamide therapy (6 pulses, administered every 4 weeks) led to substantial symptomatic improvement, complete regression of pulmonary infiltrates and marked recovery of cardiac function (LVEF 47 %). CONCLUSION: Serological detection of elevated ANCAs is not necessary for diagnosis of EGPA. Only 30 - 70 % of patients are positive for these, particularly if neurological and/or renal rather than cardiac and/or pulmonary involvement is present. This may be a pitfall in establishing the correct diagnosis. Induction therapy with cyclophosphamide is the preferred treatment for steroid-refractory EGPA with life-threatening organ involvement.

Overview and evaluation of the value of fine needle aspiration cytology in determining the histogenesis of liver nodules: 14 years of experience at Hannover Medical School.

Fine needle aspiration (FNA) is a sensitive and specific method (95%), often helpful in characterizing suspected liver lesions. It is appropriate to distinguish between primary and secondary liver neoplasia. Moreover, in most cases, the use of cell block preparations of small specimens allows immunocytochemical evaluation to determine the nature of the primary tumour. In a retrospective study at Hannover Medical School (MHH) from 1998 to 2012 (14 years), 4,136 sonographically guided FNAs were performed. The patients provided consent and the study protocol was approved by the local ethics committee. There were 39.6% malignant and 57.5% benign lesions in the liver, while 2.8% of the cases were undetermined. FNA was non-representative in 1.1% of the cases. The diagnostic utility of highly differentiated hepatocellular carcinoma (HCC; G1) remains difficult; cell bridges with cell atypia are pathognomonic for diagnosis. Ancillary techniques and immunocytochemical investigations will increase the sensitivity and specificity, particularly by using the cell block technique.

[Splenosis--important differential diagnosis in splenectomized patients presenting with abdominal masses of unknown origin]. / Splenose -- eine wichtige Differenzialdiagnose unklarer abdomineller Raumforderungen bei splenektomierten Patienten.

A 40-year-old female patient was admitted for work-up of multiple abdominal masses. The lymphoma-mimicking tumors were detected accidentally during an ultrasound course. The past medical history was unremarkable besides a status post-traumatic splenic rupture and splenectomy. The patient was asymptomatic, especially there were no complaints of fever, night sweats or weight loss. Laboratory tests did not show pathological results. Ultrasound of the abdomen revealed multiple hypoechoic mesenterial and peritoneal enlarged tumors as well as a subhepatic mass (30 x 20 mm). Transmission computed tomography (CT) showed a normal chest, excluded abnormal thoracal masses and confirmed the multiple abdominal nodules. Microparticles were trapped only by tissue with phagocytosis function as cells of the reticulohistiocytary system in liver and spleen. Uptake of (99 m)Tc-labeled microparticles is specific for splenic tissue. All abdominal masses were detectable by single photon emission computed tomography (SPECT) after intravenous administration of this radiotracer. Ultrasound-guided biopsy proved the presence of spleen tissue with follicular hyperplasia. In conclusion, we report a case of post-traumatic splenosis. In 16 - 67 % of patients who experienced traumatic splenic rupture autotransplanted spleen tissue can be detected. Splenosis therefore is an important differential diagnosis of abdominal masses in splenectomized patients.

[Intestinal tuberculosis: Easier overlooked than diagnosed]. / Darmtuberkulose: leichter zu übersehen als zu sichern.

Intestinal tuberculosis: Easier overlooked than diagnosed. The medical history of two Asian immigrants suffering from intestinal tuberculosis demonstrates the difficulties in finding the correct diagnosis. Intestinal tuberculosis resembles Crohn's disease with regard to clinical symptoms, macroscopic and microscopic intestinal findings. Sonographic, radiologic, endoscopic, and histological examinations facilitate distinguishing both entities. Diagnosis of intestinal tuberculosis is made by identification of the causative microorganism in tissue specimens. As this may be difficult and time-consuming, a therapeutic trial with anti-tuberculous agents may be warranted.

Familial isolated parathyroid adenoma in a consanguineous family.

The 23-year-old Caucasian male propositus presented with symptomatic hypercalcemia, hypophosphatemia and normocalciuria for 2 months. His 29-year-old brother had undergone an operation for recurrent parathyroid adenoma at age 26 and 28. No other member of the family was affected. His father and mother were second-degree relatives. Laboratory studies showed primary hyperparathyroidism (pHPT), while the remaining endocrine studies and genetic testing for multiple endocrine neoplasia 1 and 2A were normal. Technetium-cardiolite scintigraphy and ultrasound scans revealed a parathyroid mass at the left lower neck. Apart from bilateral hearing loss due to gentamicin treatment as a pre-term child, the patient was in of good health. Signs or symptoms of other endocrinopathies were absent. The patient was referred for parathyroidectomy with subsequent autotransplantation of the remaining glands into his sternocleidomastoid muscle. Histological examination revealed an adenoma with oncocytic differentiation, similar to that seen in his brother. The disease may follow a recessive mode of inheritance or may be due to a dominant germ-cell mutation in one of the parents. The presented case may ultimately help in elucidating the molecular genetic basis of this rare form of pHPT.

[Follow-up of differentiated thyroid cancer patients using rhTSH--preliminary results]. / Nachsorge des differenzierten Schilddrüsenkarzinoms unter Verwendung von rhTSH--vorläufige Ergebnisse.

AIM: In the follow-up of patients with advanced stage thyroid cancer radioiodine scintigraphy, F-18-FDG PET and tumormarker hTg using stimulation with recombinant human TSH (rhTSH) were compared to the results of same diagnostic procedures during TSH-suppression or endogenous TSH-stimulation. METHODS: 30 patients were investigated in hypothyroidism and after application of rhTSH regarding the serum hormone concentrations, hTg, radioiodine scans and FGD-PET scans. RESULTS: Radioiodine avidity and FDG uptake were significantly higher in 7/30 and 3/5 patients, respectively, compared to endogenous stimulation or TSH-suppression. In about one third of patients hTg increased more than 30%. CONCLUSION: Our preliminary results indicate a sufficient feasibility and sensitivity of rhTSH not only in the follow-up by hTg and radioiodine scan but also in FDG-PET.

Fluorescence in situ hybridization and surface markers of fine needle aspiration specimen confirm extramedullary myeloblastoma in a patient with chronic myeloid leukemia.

We report on a patient with chronic myeloid leukemia (CML) with a rapidly growing left cervical tumor 5 months after the initial diagnosis of CML. This tumor was diagnosed as a very early manifestation of extramedullary myeloblastoma by a minimally invasive method. A fine needle aspirate (26-gauge needle) was obtained from the tumor. Morphological and cytochemical analysis of the aspirate revealed 19% undifferentiated blasts. The immunophenotype was suggestive of a myeloid differentiation of the blasts (CD33+). The CML origin of the blasts was confirmed by the detection of the bcr-abl gene rearrangement in the blasts by two-color fluorescence in situ hybridization (FISH). We conclude that fine needle aspiration in combination with immunophenotyping and FISH analysis of the aspirate is a minimally invasive and rapid diagnostic tool to confirm extramedullary manifestation in CML. To our knowledge, this is the first case of extramedullary myeloblastoma confirmed by this combined technique.

Infiltration of the central nervous system by a granulosa cell tumor immunostained by antibodies against inhibin.

Involvement of the CNS by a granulosa cell tumor of the ovary is rare. We describe a patient with leptomeningeal and cerebral cortex infiltration by this tumor. The diagnosis was confirmed by CSF cytology and immunocytochemistry using monoclonal antibodies against human inhibin.

Immune thyroiditis after transplantation of allogeneic CD34+ selected peripheral blood cells.

A 28-year-old female patient underwent allogeneic PBSCT from her HLA-identical sister for AML in first CR. CD34+ cells were positively selected from PBPC using immunoaffinity columns. She received 8.0 x 10(6) CD34+ cells/kg and 1.74 x 10(6) CD3+ cells/kg body weight (BW). The patient developed acute GVHD III and mild limited chronic GVHD. Thirteen months after transplantation severe thyrotoxicosis requiring plasmapheresis occurred. Immune thyroiditis was confirmed cytologically by lymphocytic infiltration in a fine needle aspirate and by elevated thyroid-Ab-titers. The patient's donor had received thyroid hormone substitution for 10 years for hypothyroidism. The most probable cause of immune thyroiditis after allogeneic BMT is the transfer of antithyroid donor lymphocytes. These lymphocytes can also be transferred with a CD34+ selected peripheral stem cell graft. The transplantation of lymphocyte-depleted autologous bone marrow or PBPC grafts after myeloablative treatment is increasingly considered as potential treatment of severe autoimmune diseases. This case demonstrates that even low numbers of lymphocytes are capable of transferring autoimmune disorders.

[Scintigraphy using 131I in oxyphilic carcinomas of the thyroid gland]. / Szintigraphie mit 131J bei oxyphilen Karzinomen der Schilddrüse.

The aim of the study was to ascertain the role of 131I scintigraphy (RIS) in the follow-up of oxyphilic thyroid carcinomas (OTC). It is discussed that metastases (M) and local recurrencies (LR) are incapable of accumulating 131I sufficiently; therefore, the usual strategy of RIS cannot be used for follow-up. The re-examination of 91 patients suffering from OTC showed that 10/20 patients with M/LR did have a positive uptake of 131I, which could be used for therapy in 8 patients. An ablation of M using high-dose 131I therapy could be demonstrated in three younger patients who had cervical lymph node M 3 months after thyroidectomy as an early manifestation of their disease. In three patients RIS first led to the metastatic site. The clinical course of patients with distant M that developed at a later stage was unfavourable, even though they did accumulate 131I. Patients with positive uptake of 131I in M/LR were significantly younger (55a) than patients who had no uptake (67a) and belonged more often to stage I and II of UICC, namely 7/10 vs 2/10. RIS should be used especially in an early interval after thyroidectomy and individually for follow-up: as a diagnostic method and therapeutic instrument.

Helicobacter pylori infection and serum pepsinogen A, pepsinogen C, and gastrin in gastritis and peptic ulcer: significance of inflammation and effect of bacterial eradication.

OBJECTIVES: To study the relationship between Helicobacter pylori infection, gastric inflammatory scores, and fasting gastrin and pepsinogen A and C concentrations, and to evaluate the effect of treatment on these parameters. METHODS: Gastrin and pepsinogen A and C concentrations were measured in 36 patients with gastritis, 10 gastric ulcer patients, 12 duodenal ulcer patients, and in 15 subjects with normal gastric mucosa, by standard radioimmunoassay techniques. Fifteen patients with H. pylori infection underwent triple therapy (bismuth subsalicylate, amoxicillin, metronidazole) and were reassessed 1 month later. RESULTS: Fasting gastrin and pepsinogen A and C concentrations were significantly higher in H. pylori-positive gastritis and peptic ulcer patients than in subjects with normal mucosa and in patients with H. pylori-negative gastritis. There was a significant correlation between inflammatory scores and serum gastrin (r = 0.45, p < 0.0001), and pepsinogen A (r = 0.33, p < 0.006) and pepsinogen C (r = 0.55, p < 0.0001) concentrations. Neither sex nor age affected basal gastrin and pepsinogen concentrations. Eradication of H. pylori infection was successful in 12 patients and resulted in a significant fall in serum gastrin and in pepsinogen A and C concentrations, and in a concomitant improvement of the inflammatory scores. Serum peptide levels and gastritis scores were unchanged in those patients in whom H. pylori infection persisted. CONCLUSIONS: These findings suggest that hypergastrinemia and hyperpepsinogenemia are secondary to H. pylori infection and are related to mucosal inflammation.

[The clinical course of oxyphilic carcinoma of the thyroid]. / Klinisches Verhalten oxyphiler Karzinome der Schilddrüse.

In a total of 1665 patients with malignant thyroid neoplasms 90 oxyphilic thyroid carcinomas (OTC) were found of whom 55 could be re-examined and newly classified. Morphological and clinical parameters influencing the clinical course were determined. During a mean follow-up period of 6.5 y metastases or local recurrent disease occurred in 12 patients (24%). Apart from 3 early manifestations of metastases, 9 patients developed recurrent disease within, on average, 4.7 y after thyroidectomy: local lymph node metastases and local recurrences occurred within an average of 5.4 y, distant metastases after only 2.7 y. Thyroglobulin proved to be reliable for follow-up with a sensitivity of 88% on levothyroxine and 75% on endogenous TSH-stimulation (specificity: 98%). The frequency of metastases and local recurrences correlated with age at the time of tumor diagnosis, the degree of invasiveness and the local tumor extension (pT4 vs. pT1-3), whereas other factors such as the absolute diameter of the tumor or patient's sex had no influence on the clinical course. The survival probability for 5 and 10 years was 95 and 75%, respectively. All OTC patients should be examined regularly at least once a year by cervical sonography and thyroglobulin measurement. Because 18% recurrences occurred within 4.7 y such examinations should be repeated beyond year 5 after thyroidectomy.

Histomorphometry in paraffin sections of thyroid tumors.

Planimetric features of cell nuclei in paraffin-embedded histological sections of benign and malignant thyroid tumors, as well as normal thyroid tissue as control, were determined by means of a semiautomatic system. The main aim was to objectify possible quantitative differences between adenomas and carcinomas of the thyroid gland, which had recently been reported by several authors. For each nuclear profile, the area, the maximum diameter as well as two form factors were calculated. Statistical analyses of morphometric differences between normal controls, oxyphilic adenomas and carcinomas, and between follicular adenomas and carcinomas were performed using the T-test, a multivariate test, and a discriminant analysis. The tests revealed significant differences between controls and all other groups. The most striking result, however, was the total discrimination between follicular adenomas and carcinomas, with no false reclassification. Carcinomas had a higher mean nuclear area and diameter and a lower form factor. A similar reliability of discrimination could be obtained by comparing these morphometric values in oxyphilic adenomas and carcinomas. When using a test set of 9 cases (4 adenomas, 5 carcinomas), only one adenoma was falsely reclassified as a carcinoma by the discriminant analysis. Our results thus allow the conclusion that planimetric nuclear measurements indeed seem to be useful for the objectivation of cytomorphologic differences between adenomas and carcinomas of the thyroid gland.

Evaluation of a monoclonal antibody for detection of Helicobacter pylori in a direct immunofluorescence test.

A monoclonal antibody was developed for detection of Helicobacter pylori in gastric tissue sections in a direct immunofluorescence test. On a comparison of the immunofluorescence test with standard methods for detection of Helicobacter pylori, i.e. culture, the urease activity test and histological examination of tissue sections, using 158 biopsy specimens, 30 specimens were positive in all methods and 64 negative. In the remaining cases comparison was not possible because either immunofluorescence (29 specimens) or the standard methods (16 specimens) gave ambiguous results. The direct immunofluorescence test may have potential as an alternative to standard methods, but further testing in a defined patient population is necessary.

The role of omeprazole (40 mg) in the treatment of gastric Helicobacter pylori infection.

The efficacy of omeprazole in the elimination of Helicobacter pylori was investigated in a prospective randomized-controlled trial. 50 patients with upper gastrointestinal symptoms and chronic active H. pylori-associated gastritis were allocated to one of the following four therapeutic schedules: 1) omeprazole 40 mg/d for 4 weeks (n = 13); 2) bismuth subsalicylate (BSS) 3 x 600 mg for 4 weeks (n = 12); 3) omeprazole plus BSS for 4 weeks (n = 13); 4) triple therapy (BSS for 4 weeks, amoxicillin 3 x 750 mg and metronidazole 3 x 400 mg for 10 days) (n = 12). Clinical symptoms, endoscopic and histologic findings, and H. pylori status were reassessed immediately after therapy, and 1 and 6 months later. After cessation of therapy bacterial clearance rates were: 1) omeprazole 2/13 (15%); 2) BSS 6/12 (50%); 3) omeprazole plus BSS 5/13 (38%); 4) triple therapy 10/12 (83%). The degree of density of gastric mucosal infestation with H. pylori and the degree of activity of gastritis was reduced in all treatment groups but was most prominent after triple therapy. Clinical symptoms improved in all treatment groups. One and six months after completion of therapy H. pylori eradication rates were: 1) omeprazole 0/13 (0%); 2) BSS 1/12 (8%); 3) omeprazole plus BSS 1/13 (8%); 4) triple therapy 10/12 (83%). Our study shows that 40 mg/d omeprazole is ineffective in eradicating H. pylori. Dual therapy with omeprazole and bismuth subsalicylate does not improve bacterial elimination. Only triple therapy effectively eradicates H. pylori.

[Diagnostic value of the prick test and tissue RAST in allergic nasal polyposis]. / Die diagnostische Wertigkeit von Pricktest und Gewebs-RAST bei der allergischen Polyposis nasi.

Nasal polyposis is often accompanied by an allergy against inhaled allergens or various foods and drugs. We studied the relationship between nasal polyposis and type-I allergy, using a preoperative skin test on 43 patients with nasal polyposis. This was followed by RAST test of serum, nasal secretion and homogenized tissue from the polyps removed. The rest of the polyp material was examined histologically and cytologically for tissue eosinophilia. A type-I allergy was proved in 40% of the patients by the presence of the same IgE antibodies in the skin test and all the RASTs, accompanied by a distinct eosinophilia in the polyp tissue. In a further 40% of the cases most of the tests were positive, suggesting a probable allergic disposition. These results support the theory of an allergic genesis of many nasal polyps. The tissue RAST especially is of great diagnostic value. Thus, postoperative anti-allergic treatment of these patients should be successful.

Epidemiology and treatment of gastric Campylobacter pylori infection: more questions than answers.

Two-hundred and ten consecutive patients undergoing routine gastroscopy were additionally investigated for evidence of Campylobacter pylori (C.p.). 106 patients were positive in one or more tests: 99.1% using a rapid urease detecting test (CLO-test), 80.2% histology, 78.3% cytology and 60% culture. We found no difference between the CLO-test results from biopsies taken from different parts of the stomach in individual patients. C.p. was found in 100% of patients with significant chronic antral gastritis, 67.7% with gastric ulcers, 65% with duodenal ulcers and in 12.1% of normal individuals. The C.p. infection was apparently eliminated in 50% of cases treated with bismuth subsalicylate (BSS) for four weeks. The combination of BSS with amoxicillin, tinidazole or an H2-receptor antagonist offered no advantage over BSS alone. Treatment with BSS led to improvement in symptoms and histological findings including healing of ulcers in patients with or without persistent C.p. infection. The recurrence of C.p. infection after apparently successful treatment was, however, 75% in 4 weeks. In conclusion, C.p. infection correlates strongly with the presence of chronic gastritis, and significantly with gastric and duodenal ulceration. The best diagnostic approach is the combination of a rapid urease detecting test and histology. C.p. infection is of long duration and difficult to eliminate. The most effective treatment for C.p. infection remains BSS as single agent.

Value of the cytologic analysis of fine needle aspiration biopsy specimens in the diagnosis of pancreatic carcinomas.

Between 1982 and 1986, 410 preoperative percutaneous fine needle aspiration (FNA) biopsies of the pancreas were performed on 316 patients clinically suspected of having a malignant pancreatic tumor. Of 58 patients with pancreatic carcinomas subsequently confirmed by histologic investigation, the FNA biopsy yielded a cytologically positive diagnosis of carcinoma in 39 cases (67.2%) and suspicious findings in another 5 cases (8.6%). In 14 cases of malignancy (24.1%), the FNA puncture failed to sample material from the tumor; hence, the cytologic evaluation yielded false-negative results. Of 21 patients with inflammatory disorders of the pancreas, cytologically suspicious cells were observed in 5 cases (23.8%); in none of those 5 cases did the histologic examination show any evidence of carcinoma. This indicates that caution should be taken not to cytologically over-diagnose cases of pancreatitis. On the whole, cytology proved to be a valuable method for the diagnosis of pancreatic carcinoma; it provided the highest rate of positive results in comparison with other modern clinical diagnostic methods. Furthermore, cytology may improve the diagnostic results even in those cases with clinically negative or merely suspicious findings. FNA punctures of the pancreas produced no serious complications in this series.

Binucleated cells in a human renal cell carcinoma with 34 chromosomes.

Cytogenetic analysis of a human renal cell carcinoma revealed a near-haploid chromosome number of 34 with the loss of one chromosome #1, #2, #3, #6, #7, #9, #10, #12, #13, #17, #18, and #21. Binucleated cells were observed in histologic, cytologic, as well as in cytogenetic preparations. The paper briefly discusses the binucleation-polyploidization as a possible compensatory mechanism to maintain the genetic balance in near-haploid cells.