[Blast-like tumor tissue in cervical lymph node with expression of placental alkaline phosphatase]. / Blastäres Tumorgewebe in Halslymphknoten mit Expression plazentaalkalischer Phosphatase.

We report a case of ALK1-positive anaplastic large cell lymphoma with expression of placental alkaline phosphatase (PLAP) in many tumor cells. Initially, due to the positivity of tumor cells for CD30 and PLAP, lymph node metastasis of a germ cell neoplasm was discussed. Anaplastic large cell lymphomas of T­cell lineage form a group of rare non-Hodgkin lymphomas with heterogeneous morphological and immunohistochemical appearance. They may imitate other neoplasms, such as large cell B­cell lymphomas, metastasis of a carcinoma, melanoma, embryonal carcinoma or seminoma, rhabdomyosarcoma and inflammatory myofibroblastic tumor. Only an extended immunohistochemistry panel leads to an accurate diagnosis.

Improving the reproducibility of the Gleason scores in small foci of prostate cancer--suggestion of diagnostic criteria for glandular fusion.

High upgrading rates of Gleason score 6 to 7 carcinomas between biopsy and radical prostatectomy specimens may be produced by change of fused glands of pattern 3 to pattern 4. Therefore, inter-observer reproducibility of fused and non-fused glands in biopsy specimens was analysed. Images of H&E stained slides of glands of carcinomas with Gleason score 6 and 7 (3 + 4) with and without glandular fusions with different lens magnification were analysed by 4 specialized genitourinary pathologists and 3 non-specialized pathologists. The definition of glandular fusion was a complete lack of any stromal fibres between a minimum of two glands and only one line of nuclei within the area of fusion. Overall agreement and inter-observer reproducibility of fused versus non-fused glands of non- and uro-pathologically specialized pathologists were lower in lens magnification of 50× in contrast to 200×. The inter-observer reproducibility of fused glands by specialized observer was higher than that of non-specialized pathologists. The results support the importance of strict but practicable criteria for the diagnosis of fused tumor glands in order to decrease the interobserver variability of Gleason scores, particularly in non-specialised pathologists.

[Importance of second opinions on histology of prostate biopsy specimens]. / Bedeutung der Zweitmeinung bei Prostatabiopsien.

OBJECTIVE: The significance of a second opinion on the histological findings of prostate carcinomas as well as suspicious lesions on core needle biopsy specimens was studied in cases from the year 2008. STUDY DESIGN: A total of 920 core needle biopsy specimens of the prostate were stained with H & E and when necessary immunohistochemical analyses were performed with basal cell markers p63, 34ßE12, PSA and AMACR (P504 S) and neuroendocrine markers such as synaptophysin and chromogranin. The modified Gleason grading system was used. RESULTS: In 43.5% of suspicious lesions adenocarcinomas of the prostate were found. In 53.2% the findings of atypical small acinar proliferations or high-grade prostatic intraepithelial neoplasia (HGPIN) were confirmed with a recommendation of serum PSA and morphological controls. The suspicion of prostatic carcinoma could be confirmed in 87.2% by the diagnosis of adenocarcinoma. After Gleason grading 82.8% of all diagnosed carcinomas had scores 6 or 7(3 + 4) and belonged to the group of low grade carcinomas. High grade carcinomas were without diagnostic problems. CONCLUSION: A second opinion on the histological analysis of suspicious lesions of the prostate as well as of confirmation of Gleason grading is a very important point of quality management of diagnostic steps of prostate carcinomas and may be helpful for different therapeutic strategies.

[Bone metastasis of prostatic cancer imitating Paget's sarcoma]. / Ossäre Metastase eines Prostatakarzinoms simuliert ein Paget-Sarkom.

HISTORY AND CLINICAL FINDINGS: A 74-year-old man presented with bone pain of the right hip, night sweat and weight loss for 18 months. The diagnosis of Paget's disease was confirmed four months before admission, but pain and elevated serum alkaline phosphatase levels remained despite treatment with i.v. bisphosphonates. The physical examination showed no specific abnormalities. INVESTIGATIONS: Laboratory findings were elevated levels of serum alkaline phosphatase (AP), CA 19-9 and CEA. Radiological and tomographic images showed an aggressive periostal reaction consistent with Paget's sarcoma. The bone biopsy revealed the presence of prostatic cancer which was confirmed in a subsequent prostate biopsy. TREATMENT AND COURSE: Because of the multiple bone and lung metastases the disease proved to be incurable and the patient received palliative therapy with flutamide. He died 12 months later. CONCLUSION: In patients with Paget's disease lacking of response to bisphosphonate administration (permanently increased AP and sustained pain) radiological and clinical re-assessment of the diagnosis is indicated and may sometimes also include bone biopsy.

[Extensive bilateral lower leg muscle necrosis after nasal application of heroin. Macroscopic and histologic findings in a 23-year-old man]. / Ausgedehnte bilaterale Unterschenkelmuskelnekrosen nach nasaler Heroinapplikation. Makroskopische und histologische Befunde bei einem 23-jährigen Mann.

Rhabdomyolysis is one of the less known complications of heroin abuse. A case of lower leg muscle necrosis after nasal application of heroin is reported with repeated resection of the necrotic muscles. Superinfection with a methicillin-resistant Staphylococcus aureus (MRSA) strain was present. After 4 weeks, bilateral amputation could not be avoided. We regard a direct toxic effect of the heroin as the most probable mechanism of the muscular damage, with possible influence of the reduced oxygen delivery due to central respiratory and circulatory depression.

Limiting the diagnosis of atypical small glandular proliferations in needle biopsies of the prostate by the use of immunohistochemistry.

Prostatic biopsies containing small glandular formations suspicious of, but not diagnostic for, carcinoma represent a diagnostic dilemma, as they cannot be definitely identified as either benign or malignant. The term 'atypical small acinar proliferation' (ASAP) in the differential diagnosis of carcinoma has recently evoked considerable discussion. This study has tried to assess the biological potential of ASAP by further immunohistochemical (IHC) analysis. Biopsy-proven cases of ASAP (n=114) were analysed, in which consecutive sections still contained the suspicious lesion. IHC studies were undertaken with anti-cytokeratin 34betaE12 and the proliferation marker MIB-1. Staining with 34betaE12 revealed a complete basal cell layer in 25 cases (21.9%), a fragmented layer in 58 cases (50.9%), and absence of basal cells in 31 cases (27.2%). MIB-1 labelling indices (LIs) in these three groups were significantly higher than in benign prostatic tissue (p<0.001) and reached the level of low-grade prostatic carcinoma (p>0.05). The suspicious morphology of ASAP on haematoxylin and eosin-stained slides was supported by the finding of elevated proliferative activity. Subgroups were revealed by immunohistochemical assessment of basal cell status and cases without basal cells were diagnosed as carcinoma. Nevertheless, rebiopsy is recommended if radical surgery is planned, to exclude insignificant cancer. Cases with a complete or fragmented basal cell layer were regarded as non-malignant. Whether a fragmented basal cell layer reflects a technical artefact or transition to carcinoma is unknown, but the proliferative activity of both lesions was increased and corresponded to that of low-grade prostatic carcinoma. In these cases, therefore, at least clinical follow-up is strongly recommended and repeat biopsies are encouraged.

Acute measles gastric infection.

We describe the case of a 44-year-old man who was referred for gastroscopy because of abdominal pain. During endoscopy, inflammatory changes of the antrum and corpus mucosa were clearly visible, and biopsy samples from the antrum and corpus mucosa were taken. At histology, routine hematoxylin and eosin staining showed characteristics indicative of so-called ex-Helicobacter pylori-gastritis that had developed after antibiotic treatment 2 years ago. Additional large, bizarre inclusion bodies and clusters of multinucleated giant cells were located in the surface epithelium and within the lamina propria. These giant cells had an appearance similar to that of Warthin-Finkeldey cells, which can be found during the prodromal phase of measles infection. Anti-measles virus immunochemistry showed a strong positivity for measles virus antigen within the giant cells. Based on these results, the final diagnosis of morbilliform gastritis was made. To our knowledge, no case of measles gastritis has been described in the literature. Our case report confirms the systemic character of measles virus infection and confirms that measles viral replication can involve the gastric mucosa in addition to the conjunctiva, lung, and intestina.

Nondetected tumor (pT0) after prolonged, neoadjuvant treatment of localized prostatic carcinoma.

OBJECTIVES: 135 patients with stage T1-3N0M0 prostatic carcinoma were submitted to prolonged PSA-monitored neoadjuvant endocrine treatment (PPNET). The rate of pT0 reports was three times higher (15%) than after the standard 3-month therapy (5%). The present work was done to elucidate the initial characteristics of these tumors, to see if additional workup of these prostatectomy specimens is able to detect tumor vestiges and, if so, to describe their morphology. METHODS: The original clinical and histopathological data of 20 pT0 cases were reviewed and an additional histopathological workup of the prostatectomy specimens was done. RESULTS: The majority of patients had initially small (9 patients cT1, 8 patients cT2, 3 patients cT3) and well-differentiated tumors (18 patients Gleason score <7). Microscopic assessment of 4,503 slides revealed very small tumor remnants (mean volume 0.2 ml) in 13 of the 20 prostatectomy specimens. Severe tumor regression was seen in 3 cases, slight to moderate regression in 10 cases. CONCLUSIONS: A pT0 report following detailed routine histopathological workup has to be regarded as a maximal therapeutic effect, but not as tumor elimination. PPNET clearly increases the rate of pT0 reports, implicating that the conventional 3 months of pretreatment does not exploit the possibilities of neoadjuvant therapy.

Neuroendocrine differentiation in prostatic carcinomas: histogenesis, biology, clinical relevance, and future therapeutical perspectives.

Since the introduction of immunohistochemistry, there is an increasing interest in neuroendocrine (NE) differentiation in prostatic carcinomas. Focal NE differentiation in prostatic adenocarcinomas is a very frequent finding. It is subject of numerous studies, since a negative impact on prognosis and an important role in antiandrogen therapy failure are suspected. NE-differentiated small-cell carcinoma is a very rare tumor comprising 0.5-2% of all prostatic carcinomas. Nevertheless, although very rare, it is of clinical importance because it is one of the most aggressive tumors of the prostate with a very poor prognosis. This review is focused on actual concepts of histogenesis, cell biology, clinical implications, and possible future therapeutic perspectives of these two tumor entities.

[A fulminant course of infection after splenectomy]. / Foudroyant verlaufende Sepsis nach Splenektomie.

A report is given of two patients with a history of splenectomy many years previously due to traumatic rupture. No vaccination was given to either patient. From a state of good health, both patients developed fulminant, therapy-resistant sepsis with proof of Streptococcus pneumoniae in the blood culture. Autopsy findings were similar to Water-house-Friderichsen-syndrome. In conjunction with the history of splenectomy, the final pathological diagnosis was a so-called OPSI syndrome. This postsplenectomy sepsis is discussed further.

Osteoclast-like giant cell tumour of the pancreas presenting as a pseudocyst-like lesion.

A 57-year-old male patient presented with a cystic lesion in the tail of the pancreas, which was considered to be a pseudocyst. He was treated by cystojejunostomy but one year later a tumour was found to have invaded the stomach and jejunum. This was an osteoclast-like giant cell tumour containing a small area of typical ductal adenocarcinoma. Immunohistochemical staining revealed that the pleomorphic tumour cells were positive for cytokeratin, epithelial membrane antigen, vimentin and the proliferation marker MIB-1. The osteoclast-like giant cells and some small histiocytic cells stained for leukocyte common antigen and histiocytic markers and were negative for MIB-1. At autopsy, tumour rests were found in the pancreas but there were no metastases. Osteoclast-like giant cell tumours of the pancreas may present as cystic lesions and should be included in the differential diagnosis of pseudocysts.

[Fulminant infection outcome after splenectomy]. / Foudroyant verlaufende Sepsis nach Splenektomie.

A report is given of two patients with a history of splenectomy many years previously due to traumatic rupture. No vaccination was given to either patient. From a state of good health, both patients developed fulminant, therapy-resistant sepsis with proof of Streptococcus pneumonlae in the blood culture. Autopsy findings were similar to Waterhouse-Friderichsen-syndrome. In conjunction with the history of splenectomy, the final pathological diagnosis was a so-called OPSI syndrome. This postsplenectomy sepsis is discussed further.

Lethal complications in a case of sigmoid diverticulitis. A case report.

A 61-year-old female complaining of arthralgia was repeatedly treated with antibiotics and also with prednisolone. A chronic polyarthritis was assumed. In hospital, leukocytosis of 21.000 was found one day before death as well as moderate anemia. Colonoscopy was rejected by the patient. A computer tomography revealed destructive arthritis of the symphysis, vertebral osteochondrosis L5/S1, and sigmoid diverticulosis. The patient died with clinical signs of central dysregulation. At autopsy, a covered perforation of a sigmoid diverticulum with purulent peridiverticulitis was found. The 5th lumbal vertebra and the symphysis showed hematogenic abscesses. Microabscedating pneumonia, purulent meningitis and hypophysitis, and mycotic aneurysm of the basilar artery with lethal rupture were further results of hematogenic spread. Death was caused by massive subarachnoidal hemorrhage. This history is not untypical for elder patients with complicated diverticular disease. The intestinal perforation is often clinically occult due to only few and unspecific symptoms which cannot be exactly attributed to the colon. In the last ten years, we have found lethal complications of sigmoid diverticulitis at a frequency of 0.32% (5 cases in 1.557 subsequent autopsies). The clinical differential diagnosis included diverticulitis in none of the cases. This underlines the importance of autopsies for quality control in medicine, because modern diagnostic methods such as computer tomography were not able to give the correct diagnosis in these cases.

[Experiences from consultation in prostatic diseases]. / Erfahrungen aus dem Konsiliardienst für Prostataerkrankungen.

With the introduction of the terms atypical adenomatous hyperplasia (AAH) and prostatic intraepithelial neoplasia (PIN), the spectrum of prostatic diseases has been distinctly enlarged. With more sophisticated diagnostics, however, diagnostic and differential diagnostic problems grow more important. At the institute of pathology in Singen, this issue is reflected by the increasing use of the uropathologic consultation service since 1989. The purpose of this paper is to demonstrate typical diagnostic and differential diagnostic problems in the pathology of the prostate on the basis of this consultation service. 573 submitted prostatic cases were evaluated and the final diagnoses were compared to the preliminary diagnoses by the primary pathologist. Frequent differences could be detected in the 3 following groups: 1. Differentiation of sclerosing adenosis versus well differentiated adenocarcinoma 2. Differentiation of AAH versus well differentiated adenocarcinoma 3. Differentiation of high grade PIN versus poorly differentiated adenocarcinoma 4. Differentiation of glandular G II a versus G II b carcinomas. Possible decision guidelines are presented.

[Neurocysticercosis]. / Neurozystizerkose.

A 54-year-old female patient with a 10-year history of ventriculoperitoneal shunt resulting from communicating hydrocephalus of undetermined aetiology is reported. Transient gait disturbances and cerebral infarction at the age of 46 did not lead to further insights into the nature of the disease. After many years with only occasional disturbances, a distinct organic brain syndrome developed. Thorough examination led to a tentative diagnosis of neurocysticercosis; this was based on the history, liquor diagnosis and cerebral microcalcifications in CT. Despite the initiation of specific therapy, the patient died of the sequelae of the disease. At autopsy, characteristic cicatricial residues of mainly basal leptomeningitis were found with collapsed parasitic cysts. Additional intracerebral mesenchymal-glial reactions were less conspicuous. Residual ependymitis had caused aqueductal stenosis. Death was due to cachexia, bronchopneumonia and a lung abscess. The clinical course and morphology of neurocysticercosis are discussed. The disease has become rare in our country, but is globally the most important parasitic disease of the central nervous system.

[Unilateral testicular tumor in adrenogenital syndrome]. / Unilateraler Hodentumor bei adrenogenitalem Syndrom.

In male patients with congenital adrenogenital syndrome (AGS), in addition to the well known adrenal changes, tumor-like testicular proliferations may be observed. They have been known from literature since decades, but have become rare due to modern therapy. Especially in the mild and inapparent cases of AGS, the "tumors" cause clinical and morphological problems. The case of a 34 year old male AGS patient is presented, who underwent resection of a large adrenal cortical adenoma at age 28. Six years later, orchiectomy followed because of a testicular tumor. In frozen sections, the "Leydig cell-like" tumor caused diagnostic difficulties. After usual embedding and examination, the diagnosis of testicular "tumor" in AGS was confirmed. By review of the literature, pathomorphogenesis and morphology of these testicular tumors as well as possible histogenesis of their cells are discussed. Because of the close similarity to Leydig cell tumors, this most important differential diagnosis is especially considered. As a rule, testicular tumors in AGS are no indication for orchiectomy.

Investigations of the horse conceptus via magnetic resonance imaging (MRI) and nitroxide spin labels as contrast agents.

Results are presented which illustrate the usefulness of Magnetic Resonance Imaging as applied to the study of living embryos. Nitroxide spin labels were employed as contrast agents to study the structure and properties of the embryos. These spin labels offer the additional advantage that they may potentially be bound to biologically important molecules thereby imparting the ability to produce contrast in the MR images to these new molecules. The horse conceptus was chosen over other embryos due to its large size. Whereas the embryos of cattle and swine are sub-millimetre in size, the horse conceptus is on the order of 10 millimetres in diameter. The availability of microscopic imaging gradient coils will allow the techniques developed in this study to be applied to the smaller embryos of other species.

Sirenomelia and anencephaly in one of dizygotic twins.

The combination of sirenomelia and anencephaly was observed in a stillborn dizygotic twin. A review of the literature revealed no other patients reported to have both conditions. Various explanations concerning the genesis of sirenomelia, and also the combination with anencephaly, are discussed.