Ayoub Nahal

New insights into the pathogenesis of glucocorticoid-induced avascular necrosis: microarray analysis of gene expression in a rat model

IntroductionAvascular necrosis of the femoral head (ANFH) occurs variably after exposure to corticosteroids. Microvascular thrombosis is a common pathological finding. Since systemic thrombophilia is only weakly linked with ANFH, we propose that microvascular vessel pathology may be more related to local endothelial dysfunction and femoral head apoptosis. Corticosteroid effects on the endothelium and resultant apoptosis have been reported. We hypothesize that corticosteroids contribute to a differential gene expression in the femoral head in rats with early ANFH.MethodsBesides bone marrow necrosis, which is a common sign in ANFH and reported in the early stages, we include the presence of apoptosis in this study as a criterion for diagnosing early disease. Forty Wistar Kyoto (WKY) rats were randomized to either a corticosteroid-treated group or an age-matched control group for six months. After sacrifice, the femoral heads were examined for ANFH. Total mRNA was extracted from femoral heads. Affymetrix exon array (Santa Clara, CA, USA) was performed on 15 selected RNA samples. Validation methods included RT-PCR and immunohistochemistry (IHC).ResultsAlthough rat exon array demonstrated a significant upregulation of 51 genes (corticosteroid(+)/ANFH(+) VS control), alpha-2-macroglobulin (A2M) gene was particularly over-expressed. Results were validated by RT-PCR and IHC. Importantly, A2M is known to share vascular, osteogenic and cartilage functions relevant for ANFH.ConclusionsThe findings suggest that corticosteroid-induced ANFH in rats might be mediated by A2M. Investigation of A2M as a potential marker, and a treatment target, for early ANFH should be carried out.

A rat model of early stage osteonecrosis induced by glucocorticoids

BackgroundGlucocorticoid (GC)-induced osteonecrosis (ON) is an important complication of medical therapy. The exact pathomechanisms of ON has not been clearly elucidated. There is a need for a reproducible animal model that better approximates the clinical scenario.MethodsTo determine the genetic susceptibility of rats to develop GC-induced femoral head ON, we evaluated 5 different inbred strains of rats (Spontaneous Hypertensive Rat, Wistar Kyoto, Wistar Furth, SASCO Fisher and Lewis). Prednisone pellets (dosage of 1.82-2.56 mg/kg/day) were implanted subcutaneously for 90. After 90 days, the femurs were resected and examined histologically and radiographically. Pathological and histological examination was performed. Hematoxylin and eosin (H & E) staining was used to delineate the femoral head osteonecrosis lesions as well as abnormalities of articular cartilage and growth plate.ResultsThe greatest differences in H & E staining were seen in the Wistar Kyoto and Wistar Furth groups. In these groups 4 out of 5 and 3 out of 5, respectively, steroid-induced rats revealed growth plate disruption with acellular areas. The TUNEL apoptosis staining assay for apoptosis revealed that 4 out of 5 of Wistar Kyoto rats, 5 out of 5 of Wistar Furth, 2 out of 4 of surviving Lewis and 2 out of 2 of the surviving spontaneous hypertensive rats had apoptotic osteocytes in trabeculae, whereas none of the Fisher rats showed apoptotic osteocytes.ConclusionsWe postulate that Wistar Kyoto, Wistar Furth and spontaneous hypertensive rats may be strains of rats more susceptible to develop ON of the femoral head while Fisher rats were the most resistant.

Malignancy in giant cell tumour of bone: is there a reproducible histological threshold? A study of three giant cell tumours with worrisome features.

1. Goedert JJ. The epidemiology of acquired immunodeficiency syndrome malignancies. Semin. Oncol. 2000; 27; 390–401. 2. Cathomas G, McGandy CE, Terracciano LM, Itin PH, De Rosa G, Gudat F. Detection of herpesvirus-like DNA by nested PCR on archival skin biopsy specimens of various forms of Kaposi sarcoma. J. Clin. Pathol. 1996; 49; 631–633. 3. Cheuk W, Wong KO, Wong CS, Dinkel JE, Ben-Dor D, Chan JK. Immunostaining for human herpesvirus 8 latent nuclear antigen-1 helps distinguish Kaposi sarcoma from its mimickers. Am. J. Clin. Pathol. 2004; 121; 335–342. 4. Lasota J, Miettinen M. Absence of Kaposi’s sarcoma-associated virus (human herpesvirus-8) sequences in angiosarcoma. Virchows Arch. 1999; 434; 51–56. 5. Lebbe C, Pellet C, Flageul B et al. Sequences of human herpesvirus 8 are not detected in various non-Kaposi sarcoma vascular lesions. Arch. Dermatol. 1997; 133; 919–920. 6. Karpati S, Desaknai S, Desaknai M, Biro J, Nagy K, Horvath A. Human herpesvirus type 8-positive facial angiosarcoma developing at the site of botulinum toxin injection for blepharospasm. Br. J. Dermatol. 2000; 143; 660–662. 7. McDonagh DP, Liu J, Gaffey MJ, Layfield LJ, Azumi N, Traweek ST. Detection of Kaposi’s sarcoma-associated herpesviruslike DNA sequence in angiosarcoma. Am. J. Pathol. 1996; 149; 1363–1368. 8. Remick SC, Patnaik M, Ziran NM et al. Human herpesvirus-8associated disseminated angiosarcoma in an HIV-seronegative woman: report of a case and limited case-control virologic study in vascular tumors. Am. J. Med. 2000; 108; 660–664. 9. Ahmed I, Hamacher KL. Angiosarcoma in a chronically immunosuppressed renal transplant recipient: report of a case and review of the literature. Am. J. Dermatopathol. 2002; 24; 330–335. 10. Fink-Puches R, Zochling N, Wolf P, Back B, Kerl H, Soyer HP. No detection of human herpesvirus 8 in different types of cutaneous angiosarcoma. Arch. Dermatol. 2002; 138; 131–132. 11. Schmid H, Zietz C. Human herpesvirus 8 and angiosarcoma: analysis of 40 cases and review of the literature. Pathology 2005; 37; 284–287. 12. Gessi M, Cattani P, Maggiano N et al. Demonstration of human herpesvirus 8 in a case of primary vaginal epithelioid angiosarcoma by in situ hybridization, electron microscopy, and polymerase chain reaction. Diagn. Mol. Pathol. 2002; 11; 146–151. 13. Ioachim HL, Adsay V, Giancotti FR, Dorsett B, Melamed J. Kaposi’s sarcoma of internal organs. A multiparameter study of 86 cases. Cancer 1995; 75; 1376–1385. Malignancy in giant cell tumour of bone: is there a reproducible histological threshold? A study of three giant cell tumours with worrisome features

The utility of MDM2 and CDK4 immunohistochemistry in needle biopsy interpretation of lipomatous tumours: a study of 21 Tru-Cut biopsy cases.

proposed classification of two tumour categories, namely (i) Toker cell derived (benign and malignant) and (ii) tumours derived from underlying carcinomas. First, it should be emphasized that the proposed precursor cells are rarely identified on haematoxylin and eosin sections. Toker described these cells in only 10% of nipples investigated, and Willman et al. demonstrated vulvar Toker cells only by means of immunohistochemistry (there is only one publication on vulvar Toker cells in the literature). One should bear in mind that although Toker cells seem appealing to some investigators, one can hardly find uniform, clear and reproducible morphological criteria in order to identify such cells. Furthermore, the immunoprofile of Toker cells has never been fully elucidated in a significant number of cases. For example, we do not know much about the expression of highand lowmolecular-weight CKs such as CK34BE12, CK5 ⁄ 6 (both high-molecular-weight CKs) and CK8 ⁄ 18 (lowmolecular-weight CK) in Toker cells. The immunoexpression of oestrogen receptor, progesterone receptor and AR is also largely unknown in this cell type. As admitted by Dr Fernandez-Flores, many cases of MPD and EMPD clearly show a different immunoprofile from that of normal Toker cells, including differences in the mucin phenotype of Toker cells and cases of vulvar Paget’s disease. The fact is that the immunohistochemical phenotype of Toker cells is reproduced by just a minority of cases with MPD and EMPD. For that reason, we believe that it is misleading to claim that so-called Toker cell pathology can currently serve as a reliable unifying concept for the cellular origin of either mammary or extramammary Paget’s disease. However, we would welcome larger, well-designed studies investigating Toker cells and their possible role in the pathogenesis of MPD and EMPD.

Primary perivascular epithelioid cell neoplasm (PEComa) of bone: Report of two cases and review of the literature

Primary perivascular epithelioid cell neoplasms (PEComas) of bone are rare mesenchymal tumors. Histologically, they are composed predominantly of perivascular epithelioid cells and have the capacity to metastasize. PEComas have been reported within intra-abdominal and intra-pelvic organs. To the best of our knowledge, only seven primary PEComas of bone have been described in the English literature. We present two cases of PEComa of bone, one arising from the distal fibula and one from the acetabulum. Both were treated by surgical excision and one also received adjuvant chemotherapy.

Pulmonary Inflammatory Myofibroblastic Tumor Invading the Gastroesophageal Junction

Pulmonary inflammatory myofibroblastic tumors are rare neoplasms of intermediate malignant potential. Most patients are asymptomatic and present with incidental findings on imaging. Dysphagia due to direct invasion into the esophagus is an extremely rare presentation of this uncommon tumor. The diagnosis is difficult to make preoperatively. Complete surgical resection offers the best chance of cure. We describe a 27-year-old man who presented with progressive dysphagia and the diagnosis was only revealed after en bloc resection of the esophagus, cardia, and left lower lobe.

Malignant epithelioid hemangioendothelioma with spindle phenotype: report of an unusual case diagnosed by fine needle aspiration cytology.

BACKGROUNDnEpithelioid hemangioendothelioma (EHE) is a rare sarcoma of vascular differentiation that involves various sites and is rarely diagnosed by cytology.nnnCASEnA thigh mass in a 36-year-old woman was aspirated. Cytologic examination showed a population of single cells of predominantly spindle morphology. The cells were large, with abundant cytoplasm, and possessed cytoplasmic processes. The nuclei were small and monomorphic and had a single conspicuous nucleolus. A minority of cells had a polygonal shape. Occasionally a perinuclear dense, round cytoplasmic condensation was present in the absence of a clear-cut intracytoplasmic luminae. Necrosis was noted. The tumor expressed vascular markers and was labeled as malignant EHE because of the spindle cell morphology, marked cellularity and presence of necrosis.nnnCONCLUSIONnOn cytology, malignant EHE is a very difficult diagnosis to render, especially when the tumor displays spindle cell morphology. In such cases, the differential diagnostic list is that of spindle cell lesions, especially of fibroblastic-myofibroblastic nature. Including endothelial markers in the immunohistochemical panel is crucial to reach the diagnosis. Also, the presence of perinuclear cytoplarmic condensation should be interpreted as evidence of endothelial differentiation on cytology, even in the absence of clearcut intracytoplasmic luminae.

Transoral Endoscopic Resection of Esophageal Liposarcoma

A 63-year-old man presented with a 1-month history of dysphagia. Endoscopy showed the patient had a mass in the cervical esophagus. Multiple biopsy specimens were taken, which were inconclusive for a diagnosis. A positron-emission tomography scan showed a hypermetabolic lesion. A transoral endoscopic approach was used to resect the tumor. Final histologic examination revealed a completely resected low-grade liposarcoma.

Primitive neuroectodermal tumor (PNET) as somatic-type malignancy arising from an extragonadal germ-cell tumor: clinical, pathological and molecular features of a case.

We report a rare case of a 34-year-old man with a right axillary mass. Ten years previously, he had been diagnosed with a right scapular nonseminomatous germ-cell tumor consisting of teratoma, completely resected without any further treatment. Presently he was found to have a metastatic malignant small round cell tumor consistent with a secondary somatic malignancy arising in the background of nonseminomatous germ-cell tumor, teratoma, yolk sac tumor, and primitive neuroectodermal tumor with distinct chromosome 22 translocation. Although the patient initially responded well to chemotherapy with etoposide, cisplatin, ifosfamide and mesna, he relapsed shortly after.

Subject Index Vol. 52, 2008

Analytical and Quantitative Cytology and Histology: Volume 29, Number 6 (December 2007), 2008; 52:114–116 Analytical and Quantitative Cytology and Histology: Volume 30, Number 1 (February 2008), 2008;52: 255–258 Analytical and Quantitative Cytology and Histology: Volume 30, Number 2 (April 2008), 2008;52: 373–376 Analytical and Quantitative Cytology and Histology: Volume 30, Number 3 (June 2008), 2008;52:505– 508 Analytical and Quantitative Cytology and Histology: Volume 30, Number 4 (August 2008), 2008;52: 631–634 Analytical and Quantitative Cytology and Histology: Volume 30, Number 5 (October 2008), 2008;52: 736–738 Acid-fast bacilli Role of Modified Bleach Method in Staining of Acid-Fast Bacilli in Lymph Node Aspirates. (Gangane et al), 2008;52:325–328 Adenocarcinoma CK5/6 in Effusions: No Difference Between Mesothelioma and Pulmonary and Nonpulmonary Adenocarcinoma. (Dejmek), 2008;52: 579–583 Cytology of Pseudomyxoma Peritonei Associated with Well-Differentiated Appendiceal Adenocarcinoma. (Siddaraju et al), 2008;52:391–394 (Letter) Diagnosis of Linitis Plastica–Type Gastric Adenocarcinoma by Endoscopic Ultrasound-Guided Fine Needle Aspiration: A Case Report. (Carter et al), 2008;52:725–728 Improved Identification of Malignant Cells in Serous Effusions Using a Small, Robust Panel of Antibodies on Paraffin-Embedded Cell Suspensions. (Grefte et al), 2008;52:35–44 Adenocarcinoma, clear cell Clear Cell Carcinoma in a Background of Endometriosis: Case Report of a Finding in a Midline Abdominal Scar 5 Years After a Total Abdominal Hysterectomy. (Rust et al), 2008;52: 475–480 Adenoma Cytologic Features of Pulmonary Alveolar Adenoma. (González et al), 2008;52:739–740 (Letter) Adenoma, microcytic Preoperative Fine Needle Aspiration Cytology Diagnosis of Microcystic Adenoma of the Pancreas: Fact or Fiction? A Report of 2 Cases. (Fitzhugh et al), 2008;52:240–246 Adenoma, pleomorphic Chondromyxoid Fibroma of the Mandible: A Diagnostic Pitfall on Aspiration Cytology of Parotid. (Daneshbod and Khademi), 2008;52:636–638 (Letter) Fine Needle Aspiration Biopsy of Pleomorphic Adenoma and Adenoid Cystic Carcinoma of the Lacrimal Gland. (Siddaraju et al), 2008;52:515– 517 (Letter) Adenoma, pleomorphic metastazing Pleomorphic Adenoma of the Parotid Gland Metastasizing to the Scapular Region: A Case Report. (Ghosh et al), 2008;52:733–735 Adnexa Cytologic Features of Primary Malignant Tumors of Skin and Adnexae. (Prayaga et al), 2008;52: 702–709 Adolescent Fine Needle Aspiration Cytology of Breast Masses in Children and Adolescents: Experience with 1,404 Aspirates. (Kapila et al), 2008;52:681–686 Adult T-cell leukemia/lymphoma Diagnostic Considerations in Prolymphocytes in Pleural Fluid: A Case Report. (Anand et al), 2008; 52:251–254 Africa Into Africa: Cytology for One World. (Kaminsky), 2008;52:399 Alcian blue Cytology of Pseudomyxoma Peritonei Associated with Well-Differentiated Appendiceal Adenocarcinoma. (Siddaraju et al), 2008;52:391–394 (Letter) Analytical and Quantitative Cytology and Histology