Tamás Tornóczky

Cell formation in the cortical layers of the developing human cerebellum.

Cell proliferation has been studied in the human cerebellar cortex between the 24th gestational week and the 12th postnatal month. Intensive cell formation has been found in the external granular layer (EGL) of the human cerebellum, where the highest cell proliferation rate occurs between the 28th and 34th gestational weeks. This is followed by a gradual decrease that lasts up to the eighth postnatal month. As late in development as the fifth postnatal month, still 30% of cells of the EGL are labeled with the monoclonal antibody Ki‐67, which is specific for dividing cells. The width of the EGL remained unchanged from the 28th gestational week to the end of the first postnatal month, when it starts to decrease and completely disappears by the 11th postnatal month. Large number of Ki‐67 labeled cells occurs in the internal granular layer (IGL) between the 24th and 28th gestational weeks. From the 36th week onwards, the labeling index is less than 1%, although a few labeled cells have always been found in this layer even in the late postnatal period. Labeled cells are distributed in the entire width of the IGL. However, from the 34th gestational week, almost all labeled cells are found among and directly below the Purkinje cells. Their position, the nuclear features, and their occasionally stained cell processes suggest that those are Bergmann glial cells. There are few Ki‐67 labeled cells in the molecular layer (ML) and in the white matter (WM) of the cerebellum throughout the examined period. It is likely that most of these are glial cells. Pyknotic index has been found to be small in all layers of the cerebellum during the examined period.

Gastrointestinal stromal tumors: A clinicopathologic and immunohistochemical study of 136 cases

The clinicopathologic features of 136 gastrointestinal stromal tumors were analyzed. The tumors occurred in 60 women and 76 men, ranging in age from 19 to 88 years (median 59 years, mean 59.2 years). Sixty-one cases arose from stomach, 38 from small intestine and 11 from colon or rectum. Abdominal cavity was indicated as tumor site in 10 cases, but the extragastrointestinal origin using strict criteria was not proved. Four locally recurrent cases and 12 metastatic samples were also included. The primary and recurrent tumors ranged in size from 0.5 to 30 cm (mean 8.3 cm). The large number of high-grade cases (85 of 112 classifiable) is alarming and emphasize the importance of oncology care. Histologically, ninety-two cases were classified as spindle cell while 11 as epithelioid GIST. Mixed cellularity was seen in 33 cases. Skeinoid fibers were present in 14 and coagulation necrosis in 40 primary cases. Ulceration observed by microscopic examination was common (36 of 110 cases, 32.7%), explaining the clinically frequently observed gastrointestinal bleeding. Unusual histological features such as stromal hyalinization and nuclear palisading were present in 30 and 27 cases, respectively. Immunohistochemical CD117 (c-kit) positivity was documented in 133 cases. Three cases with CD117 negative results were included, because their morphology was most consistent with GIST and immunohistochemical reactions excluded the possibility of other neoplasms. CD34 positivity was seen in 70%, alpha-smooth muscle actin positivity in 39.6% of examined cases. Only one case showed desmin reactivity and seven had S100 positive tumor cells. For h-caldesmon 39 cases proved to be positive (60.9% of the tested cases).

Solid and papillary epithelial neoplasm arising in heterotopic pancreatic tissue of the mesocolon

Aim—Solid and papillary epithelial neoplasm (SPEN) is an uncommon pancreatic tumour. Very rarely it has also been described outside the pancreas, usually arising from heterotopic pancreatic tissue. This report summarises all the published extrapancreatic SPENs and documents the sixth such case arising from heterotopic pancreatic tissue of the transverse mesocolon in a 15 year old girl. Methods/Results—Histological and immunohistochemical examination revealed typical papillary and solid areas composed of columnar, cuboidal, and round cells, which were focally positive for vimentin, cytokeratin, neurone specific enolase, carcinoembryonic antigen, α1-antitrypsin, α1-antichymotrypsin, and negative for neuroendocrine markers (neurofilament, PGP 9.5, chromogranin A, synaptophysin, and S100), p53, and oestrogen and progesterone receptors. Electron microscopy showed scant zymogen but no neurosecretory granules. In agreement with the flow cytometric result of diploidy, comparative genomic hybridisation (CGH) did not reveal loss or gain of genetic material, and the in situ hybridisation analysis of the RB1 and p53 genes revealed no abnormality in the 13q and 17p arms. Conclusions—Immunohistochemical and electron microscopic data support exocrine differentiation. The CGH and the flow cytometric results suggest a subtle, yet unknown genetic change, rather than a large genetic alteration. RB1 and p53 in situ hybridisation ruled out the role of deletion at these sites in the pathogenesis of SPEN. Interestingly, review of the published and the present heterotopic pancreatic SPENs identified the mesocolon as the most common anatomical site (four of six), despite the very rare occurrence of ectopic pancreatic tissue at this site.

Large cell neuroblastoma: a distinct phenotype of neuroblastoma with aggressive clinical behavior.

Among cases of undifferentiated and poorly differentiated tumors in the neuroblastoma (Schwannian stroma–poor) category, the authors histologically identified a group of rare tumors, known as large cell neuroblastomas (LCNs), that are composed of large cells with sharply outlined nuclear membranes and 1–4 prominent nucleoli.

Pathology of peripheral neuroblastic tumors: Significance of prominent nucleoli in undifferentiated/poorly differentiated neuroblastoma

The presence of large cells having simultaneously increased cytoplasmic and nuclear volume accompanied by prominent nucleoli; i.e., differentiating neuroblasts and ganglion cells, is well documented in peripheral neuroblastic tumors (pNTs), and considered as one of the signs of tumor maturation and an indication of a better prognosis of the patients. On the other hand, in 2004 it was reported that large-cell neuroblastoma composed of neuroblastic cells with only nuclear enlargement without recognizable cytoplasmic maturation behaved poorly clinically. Here we are proposing a new pNT subtype in the neuroblastoma category, in addition to the undifferentiated, poorly differentiated and differentiating subtypes: that is large nucleolar neuroblastoma (LNN) characterized by large prominent nucleoli and no or very little amount of discernible cytoplasm. LNN, whose neuroblastic cells are often large in size due to nuclear enlargement, includes those tumors previously categorized into the large-cell neuroblastoma group. LNN tumors, regardless of the size of nuclei, seem to behave aggressively with a very poor prognosis of the patients. It is speculated that nucleolar enlargement without cytoplasmic maturation in LNN tumor cells can be a sign ofMYCN amplification.

Penile chloroma in a patient with secondary acute myeloid leukemia

To the Editor: A 52-yr-old man was diagnosed as having secondary acute myeloblastic leukemia (AML), transformed from myelodysplastic syndrome. After achieving a partial remission with ‘3+7’ chemotherapy on the sulcus coronarius penis he developed a red, painful lesion. Initially it was treated as a superficial inflammation. As it did not improve, a biopsy was made and the histological result showed a chloroma (granulocytic sarcoma). There was a diffuse infiltration of variable pattern of blast cells, with a dispersed chromatin and smallto mediumsized nucleoli and more matured myeloid progenitor cells which were positive on chloroacetate esterase staining and showed very intense positivity with the Kp1 antibody reaction. Systemic antileukemic chemotherapy (mitoxantrone – cytosine arabinoside) and local irradiation was initiated. The lesion became smaller, but did not disappear. The patient died of septic shock. An autopsy revealed deep chloroma infiltration of the penis (Fig. 1). Most patients with AML have a short survival following the appearance of chloroma. The incidence of granulocytic sarcoma is 3–5% of patients with AML. It has been demonstrated on almost every part of the body. To our knowledge penile chloroma has not previously been described.

CD99-positive undifferentiated round cell sarcoma diagnosed on fine needle aspiration cytology, later found to harbour a CIC-DUX4 translocation: a recently described entity

IntroductionPoorly differentiated, small round cell sarcomasoften represent a serious differential diagnostic prob-lem. CD99 expression was initially considered to bespecific for Ewing sarcoma (ES); however, it mayalso be seen in many histologically similar neo-plasms. The differential diagnosis of these tumoursincludes mesenchymal chondrosarcoma, poorly dif-ferentiated synovial sarcoma and lymphoblastic lym-phoma. However, rarely, CD99 expression mayappear in other neoplasms of a similar morphologysuch as the blastemal component of Wilms’ tumour,small cell osteosarcoma, rhabdomyosarcoma, smallcell carcinomas, etc., further expanding the list ofdifferentials.

Ectopic pancreas tissue appearing in a mediastinal cyst.

Heterotopia of pancreatic tissue is a common developmental anomaly. Although ectopic pancreatic tissue is mostly found in the gastrointestinal tract, localization in the mediastinum is extremely rare. We report a 32-year-old male patient who had an urgent thoracotomy two years ago due to a thoracic surgery. During the thoracotomy fragments of a partly necrotic cystic mass in the right thorax were removed and decortication was performed. Two years later the patient was hospitalized again because of haemoptoe and atypical chest pain. A residual cystic mass was detected between the right hilum and the ascending aorta connecting to the pericardium, the superior vena cava and the aorta on the chest CT. After the operation a mediastinal cyst was diagnosed, with a pancreatic tissue by histology.

EBER oligonucleotide RNA in situ hybridization in EBV associated neoplasms

In virus associated diseases identification of viruses in cells can contribute to the understanding of the pathogenesis and may also help to establish the diagnosis. In the present communication, the effects of the microwave pretreatment (MWP) and that of the proteinase-K enzymatic predigestion (PKD) on EBER RNA oligonucleotide in situ hybridization (EBER-RNA-ISH) (EBER: Epstein-Barr-Encoded-(Early)-RNA) were studied. The efficacy of two EBV detecting methods, latent membrane protein-1 (LMP-1) immunohistochemistry and EBER-RNA-ISH were also compared. Our results show that microwave pretreatment enhances the intensity of the ISH signals and preserves significantly better the structure of the tissues compared with enzymatic predigestion. EBER-RNA-ISH, mainly in the nasopharyngeal carcinoma cases, showed a more frequent positivity than the immunohistochemical reaction for LMP-1, however in case of the Warthin’s tumor only the LMP-1 protein was expressed.

Angiomatoid Fibrous Histiocytoma: Pleomorphic Variant Associated with Multiplication of EWSR1-CREB1 Fusion Gene

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor which exceptionally occurs in visceral organs or bones. Histologically this is a bland, monomorphic tumor and only occasionally shows pleomorphism. Vast majority of the soft tissue cases share the same translocation and the resulting EWSR1-CREB1 gene fusion as background pathogenetic alteration. Here we report a 10-year-old boy with subcutaneous tumor of the right shoulder. Histological, immunohistochemical and FISH analyses of the case revealed pleomorphic phenotype, characteristic immunophenotype and multiplication of the EWSR1-CREB1 fusion gene in the nuclei of the tumor cells. The possible explanation of the fusion gene multiplication, its relation to the morphology and the clinical outcome are discussed in the context of the published literature.