Soft tissue high grade myoepithelial carcinoma with round cell morphology: report of a newly described entity with EWSR1 gene rearrangement.

The case of soft tissue malignant myoepithelioma is presented including clinicopathological, immunohistochemical and cytogenetic findings. A 36-year-old Saudi male patient suffered from large mass involving right scapula and right shoulder joint measuring 14x13x11 mm. Core biopsy revealed sheets and lobules of poorly differentiated small malignant cells with marked atypia and frequent mitosis. Initially, immunohistochemistry was reactive for vimentin, pan-cytokeratin, EMA and CD99. The case was negative for desmin, SMA, CD34, S-100 protein and GFAP. FISH analysis exhibited negativity for SS18 (18q11.2) gene rearrangement and positivity for EWSR1 (22q12) gene rearrangement and a diagnosis of Ewing/PNET was considered. Clinical behavior and therapeutic response did not match the diagnosis with re-evaluation. Wedge biopsy demonstrated aggregates of epithelioid cells besides calponin and P63 positivity. Final diagnosis of malignant myoepithelioma with EWSR1 gene rearrangement was issued; a new entity with aggressive course. Myoepithelial carcinoma of soft tissue exhibits a wide spectrum of cytomorphology with overlapping phenotype similar to other soft tissue sarcoma like synovial sarcoma, mesenchymal chondrosarcoma, epithelioid sarcoma as well as Ewing/PNET. Moreover, a new finding of EWSR1 gene rearrangement is recognized in malignant myoepithelioma with different fusion partners. Hence, myoepithelial carcinoma should be kept in mind in diagnosis of soft tissue tumors even with unusual phenotype and gene rearrangement.

Primary mediastinal pleomorphic rhabdomyosarcoma: a case report.

OBJECTIVE: To report a rare case of pleomorphic rhabdomyosarcoma which occurred in the mediastinum of a 34-year-old man. CLINICAL PRESENTATION AND INTERVENTION: A young male labourer presented with dyspnoea on exertion. A large mediastinal mass was detected on chest CT scan. The chest surgeons advised against open biopsy. His alpha-fetoprotein was 22,000 IU/l; based on this the diagnosis of a germ cell tumour was made and the patient was treated with a bleomycin/etoposide/cisplatin regimen. He left for his native country where an open biopsy from the mediastinum was taken and reported as pleomorphic rhabdomyosarcoma. He was given five courses of chemotherapy with doxorubicin, etoposide, and ifosfamide with mesna protection without much relief. The inoperable disease occupied the whole of the right chest and mediastinum. The enormous size of the radiation field made radiotherapy prohibitive. Finally, the patient opted for symptomatic treatment and left for his native place. CONCLUSION: This case is presented because of its difficulty in management and rarity.

Cytomorphological and immunocytochemical study of non-Hodgkin's lymphoma in pleural effusion and ascitic fluid.

INTRODUCTION: Non-Hodgkin's lymphoma (NHL) is often complicated by pleural effusion and ascites. The present study is an attempt to categorize the lymphomatous effusions according to the WHO classification, using archival material. METHODS: May-Grünwald-Giemsa and Papanicolaou-stained smears of 31 lymphomatous effusion specimens were reviewed. Of these, detailed cytological assessment was done on 12 pleural effusions and ten ascitic fluid specimens from 22 patients using the WHO lymphoma classification system. Immunocytochemical studies were performed in 21 specimens. RESULTS: Based on cytomorphological features, the 22 lymphomatous effusion specimens were categorized into lymphoplasmacytoid lymphoma (1), follicle centre cell (FCC) grade-1 (centrocytic) lymphoma (3), FCC grade-2 (centrocytic-centroblastic) lymphoma (3), FCC grade-3 (centroblastic) lymphoma (4), large cell immunoblastic lymphoma (4), lymphoblastic lymphoma (2), anaplastic large cell lymphoma (3) and miscellaneous types (2). Immunocytochemically, the lymphoma cells were T-cell (positive for CD3) and B-cell type (CD20 positive) in five and six cases respectively. CONCLUSION: Cytological examination of pleural effusion and ascitic fluid samples, supported by immunocytochemical studies, may be useful for the classification of lymphomas under the WHO system.

Cytoplasmic colloid inclusions in thyroid lesions: a cytomorphological study based on fine needle aspiration.

INTRODUCTION: Intracytoplasmic lumens (ICL) with or without magenta material and transgressing vessels are features of Hürthle cell neoplasms (HCN). After detection of intracytoplasmic colloid inclusions (CIs) including targetoid (magenta) body-like structures in the Hürthle cells (HC) in a case of Hashimoto's thyroiditis (HT), we reviewed cases of HT, thyroid neoplasms, hyperplastic nodules (HN) and colloid goitres to determine the frequency of these structures. Further, an attempt was made to find out the significance of CIs. METHODS: FNA smears of 120 HT, 101 colloid goitres, 11 HN, and 76 neoplastic goitres were examined. The presence of CIs and empty ICL were noted in epithelial cells in these lesions. An attempt was made to find out the difference between HT with and without CIs in respect of various cytomorphologic features. The groups were compared using the Fisher's exact test of probability. RESULTS: The CIs were present in 36 (30.0%) of HT, 26 (34.2%) of neoplastic goitres, 3 (27.3%) of HN, and 4 (4.0%) colloid goitres. As compared to colloid goitres, CIs were present in a significant higher number of cases in HN (P = 0.0202), neoplastic goitres (P < 0.0001), and HT (P < 0.0001). Among neoplasms the frequency of CIs in HCN (75.0%) was significantly higher than that of papillary thyroid carcinoma (PTC) (33.3%, P = 0.0466), and follicular neoplasm (14.3%, P = 0.0083). The CIs were more frequent in HC in HT and HCN but in follicular cells (FC) in other lesions. The HT cases with CIs differed significantly from those without CIs in respect of HC and their cellularity, cellularity of reactive lymphoid cells, extracellular colloid and empty ICL. CONCLUSION: Care should be taken not to diagnose HT cases with an excessive Hürthle cell component and CIs, and PTC cases with Hürthlization and CIs, as HCN in FNA smears. Based on review of the literature and our findings, it is suggested that the Hürthle cell metaplasia in HT is a survival response of FC and the presence of CIs in Hürthle cell may represent their limited ability to synthesize colloid.

Cytomorphological spectrum in scar endometriosis: a study of eight cases.

OBJECTIVE: Endometriosis due to ectopic endometrial tissue that responds to hormonal stimulation and is extremely rare in a surgical scar appearing in 0.1% of women who have undergone Caesarean section. Fine needle aspiration cytology (FNAC) can be a valuable diagnostic aid in the evaluation of these subcutaneous abdominal masses. METHODS: We present the cytomorphological spectrum in eight cases of abdominal wall endometriosis diagnosed by FNAC over a 6-year period (June 1998-June 2004) in Mubarak Al-Kabeer Hospital (Kuwait). The patients ranged from 27 to 56 years of age. Seven had a prior Caesarean section and one had a hysterectomy for fibroid. They presented 3-8 years later with nodules in/near the abdominal scar. Five cases presented with a painful nodule, fluctuant with the menstrual cycle. RESULTS: Cytological findings comprised epithelial clusters and fusiform stromal cells with numerous haemosiderin-laden macrophages. Mild to moderate epithelial atypia was observed in three cases. A diagnosis of endometriosis was rendered in all the eight cases and tissue was available in four cases. CONCLUSIONS: Endometriotic nodules need to be differentiated from other benign/malignant masses and evaluated for possible malignant transformation. FNAC provides a safe and effective tool for diagnosis thereby obviating the need for other procedures.

Cytodiagnosis of nipple discharge: a study of 602 samples from 484 cases.

To find out the gross and microscopic differentiating features between nipple discharges (ND) due to various breast lesions, smears of 602 ND samples from 484 cases were reviewed by one of the investigators (D.K.D.). The reviewed cytodiagnoses were as follows: benign nipple discharge (59.1%), inflammatory ND (6.5%), ?papillary lesions (2.5%), papillary lesions (20.6%), papillary lesions with atypia (3.8%), duct cells with atypia (0.2%), suspicious for malignancy (0.5%), malignant ND (1.2%), and inadequate (5.6%). Following review, samples with epithelial abnormalities (?papillary lesion, papillary lesion with and without atypia, duct cells with atypia, suspicious for malignancy, and malignancy) increased from 16.6% to 30.4% of adequate samples (P < 0.0001). 37.9% unilateral ND samples showed epithelial abnormalities, as opposed to 18.9% of bilateral ND samples (P < 0.0001). Bloodstained ND showed epithelial abnormalities in 41.5% samples, as compared to 22.1% of ND with other specified gross characteristics (P < 0.0001). The samples with epithelial abnormalities differed significantly from benign and inflammatory ND in respect of frequency of benign duct cells, duct cells with atypia, papillary clusters with or without atypia, malignant cells, columnar cells, red blood cells, inflammatory cells, and background lipid vacuoles (P < 0.01 to < 0.0001). The ND samples with suspicious and malignant cytology, besides the presence of malignant cells (P < 0.0001), differed significantly from rest of the lesions in respect of foam cells (P < 0.0001), red blood cells (P < 0.01), and inflammatory cells (P < 0.05). When compared with histopathological diagnosis in 20 cases, the benign or malignant nature of the lesion was correctly identified in ND in 80% cases. The ND cytologies in 7 histologically proved malignant cases were malignancy (3 cases), suspicious for malignancy (1 case), papillary lesion with atypia (1 case), papillary lesion (1 case), and benign ND (1 case).

Fine needle aspiration cytology diagnosis of a cutaneous granular cell tumor in a 7-year-old child. A case report.

BACKGROUND: Granular cell tumors are neoplasms of uncertain histogenesis, although a neural origin is favored. Most reports on the cytologic features of granular cell tumors have been on lesions from the breast or respiratory tract. However, there are only a few reports on fine needle aspiration (FNA) cytologic diagnosis of cutaneous or soft tissue granular cell tumors. CASE: A 7-year-old girl presented with a skin lesion on her right forearm of one year's duration. The FNA smears showed sheets and clusters of oval to polygonal cells with an abundant amount of granular cytoplasm. Many single, scattered cells with similar morphology were seen in the background. Immunostaining for S-100 protein showed granular cytoplasmic positivity. The tumor was diagnosed as a benign granular cell tumor. The histopathology report on the excised lesion confirmed the FNA diagnosis. CONCLUSION: The cytopathologic features of granular cell tumors presenting as skin lesions are distinctive enough to allow a correct diagnosis on FNA cytology.

Insulin-like growth factor 1-induced alterations in lumbospinal monoamine dynamics.

A wealth of evidence indicates that insulin-like growth factor (IGF-1) is involved in neurotransmitter release, synaptic plasticity, morphogenesis and regulation of gene expression. RT-PCR and immunocytochemical-based techniques revealed that IGF-1 and its receptor are highly expressed by different neuronal elements of the spinal cord lumbar enlargement. Accordingly, the present study intended to examine lumbospinal monoamine dynamics in the context of the neurotrophic factor IGF-1. Spinal release of norepinephrine (NE) represented by 3-methoxy-4-hydroxyphenylglycol (MHPG)/NE ratio was enhanced by IGF-1. This action of IGF-1 was associated with a similar increase in both tyrosine hydroxylase (TH) immunoreactivity and the level of its mRNA. In contrast, neuronal contents of serotonin and its metabolite 5-hydroxyindoleacetic acid in IGF-1-treated animals remained at control level. Genistein, a tyrosine kinase inhibitor, which by itself had no effect on NE metabolism, abolished the induction effect of IGF-1 on TH and MHPG/NE ratio. Our results suggest that IGF-1 augments the lumbospinal noradrenergic system by an intracellular mechanism involving a receptor-linked tyrosine kinase. The physiological consequences of the IGF-1 actions are discussed in terms of neuroprotection and nociception.

Manual versus image analysis estimation of PCNA in breast carcinoma.

OBJECTIVE: To compare manual to image analysis estimation of proliferating cell nuclear antigen (PCNA) expression in paraffin sections of breast carcinomas. STUDY DESIGN: Paraffin sections of 51 breast carcinomas were stained with primary antibody to PCNA. Nuclear PCNA expression in 100 randomly selected tumor cells from marked areas was manually graded from 0 to 3. Antigen expression was also calculated by a cell analysis system (CAS-200, Becton Dickinson, Elmhurst, Illinois, U.S.A.) from marked and random microscopic fields. Obtained proliferative index (PI) from both methods was compared. RESULTS: Manually calculated PI correlated strongly with the CAS-200-calculated PI (P < .01). The highest correlation was seen between the CAS-200 PI value and manually calculated PI value using grade 2 and 3 nuclei. A particularly high correlation was noted between the number of positive nuclei and antigen staining area (P < .01) as estimated by the CAS-200. CONCLUSION: Nuclear expression of PCNA and other nuclear antigens can be accurately evaluated by an image analysis system. The speed and objectivity of such machines allow the evaluation of larger parts of tissues and provide more-representative antigen expression profiles.

Value of radiologically guided fine needle aspiration cytology (FNAC) in the diagnosis of spinal tuberculosis: a study of 29 cases.

FNAC is a simple diagnostic tool for the initial evaluation of various deep seated pathological lesions. This study describes the applicability and practical aspects of the technique in establishing the diagnosis of spinal tuberculosis (TB) with the aid of radiographic guidance. The study was conducted in a major teaching hospital in Kuwait between the years 1985 and 1994. Twenty-nine patients (M:F = 18:11 and age range 8-72 years) with clinically and/or radiologically suspected spinal TB were seen in the Department of Cytology, Mubarak Al Kabeer Hospital. The patients were re-examined by either computed tomography (CT) scanning (n = 19) or fluoroscopy (n = 10) to localize the lesion for FNAC. FNAC smears were routinely stained with Papanicolaou and Diff Quik stains and one smear of each case was stained with Ziehl-Neelsen (Z-N) stain for acid-fast bacilli (AFB). Aspirated purulent material or syringe washings of dry aspirates were also submitted for microbiological cultures including AFB. Radiological and cytological findings were recorded in each case. Radiological findings included: bony rarefaction and destruction (93.1%), narrowed disc space (89.7%), soft tissue calcification (65.5%) and para-vertebral abscess formation (51.7%). Cytological findings included: epithelioid cell granulomas (89.7%), granular necrotic background (82.8%) and lymphocytic infiltration (75.9%). Smears were positive for AFB in 51.7% of cases. A positive AFB culture was obtained in 82.8% of cases, including all cases with positive AFB on smear by Z-N stain. Radiologically guided FNAC with AFB culture is a simple, reliable and practical approach to diagnosing spinal TB lesions. With a high diagnostic yield, it allows immediate initiation of specific treatment, helps to avoid invasive diagnostic procedures, and decreases hospitalization time.

A new experimental model for partial ureteric obstruction in sheep.

This study aimed to develop a new experimental model of partial ureteric obstruction in sheep. Graded obstruction of the ureter using various sized catheters (Fr 3-8) for variable durations up to 6 weeks was performed in 19 sheep. The kidneys were studied by radionuclide diuretic renography for up to 21 weeks and had histopathological examination at the end of the experiment. Catheters of Fr 3 or Fr 5 should be used to block the ureter for a minimum of three weeks to produce sufficient functional and pathological changes to be studied. The advantages and disadvantages of this model are discussed.

Heat-shock protein 72/73 and impaired wound healing in diabetic and hypercortisolemic states.

BACKGROUND: Impaired wound healing is a well-documented phenomenon in experimental and clinical diabetes. Emerging evidence favors the involvement of glucocorticoids (GCs) in the pathogenesis of this diabetic complication. Recent data indicated that a heat-shock protein (HSP) with a molecular weight of about 70 kd is expressed in wound healing and it is under the control of the hypothalamic-pituitary-adrenal axis. In view of these findings, the current study was designed to examine the influence of diabetes and the hypercortisolemic state on the expression of HSP 72/73 during wound healing. METHODS: Induction of diabetes was achieved by the intravenous injection of streptozotocin at a dose of 55 mg/kg. Subcutaneously implanted polyvinyl alcohol (PVA) sponges were used as a wound healing model. Control and diabetic animals received, respectively, subcutaneous 30-day timed-release pellets of GC (200 mg) and RU 486 (25 mg). Corresponding animals received placebo pellets. Expression of HSP 72/73 within the PVA sponges was assayed with use of Western blotting and immunohistochemical techniques. RESULTS: GCs caused a Cushing-like syndrome with weight loss and adrenal atrophy. A pronounced accumulation of constitutive HSP 72/73 was observed in the cytoplasm of various cell types including fibroblasts, macrophages, and endothelium of nondiabetic controls. The PVA sponge contents of HSP 72/73 were decreased as a function of diabetes. A similar phenomenon was seen in control animals receiving high doses of GCs. Partial normalization of the associated hyperglycemic and hypercortisolemic states of diabetes with insulin (hyperglycemia) and the GC receptor block RU 486 (hypercortisolemia) ameliorated the diabetes-related decrease in PVA sponge contents of HSP 72/73. CONCLUSIONS: The current study provides evidence that both diabetes and the hypercortisolemic state are associated with a reduction in PVA sponge content of HSP 72/73. An amelioration of these changes was achieved by the institution of RU 486 therapy. Although our data may point to the possibility that the diabetes-related decrease in HSP 72/73 is mediated at least in part by GCs, a confirmation regarding this premise awaits further investigation.

Glucocorticoid-dependent impairment of wound healing in experimental diabetes: amelioration by adrenalectomy and RU 486.

BACKGROUND: Failure of wounds to heal represents one of the major diabetic complications. Emerging evidence favors the involvement of glucocorticoids (GCs) in the pathogenesis of impaired wound healing in diabetes mellitus. OBJECTIVE: The purpose of this study was to examine wound healing potential in diabetics under conditions in which the hypercortisolemic state is normalized. DESIGN AND INTERVENTION: Linear skin incision and polyvinyl alcohol (PVA) sponge were used as wound healing models. Six groups of rats matched with respect to age, sex, and strain were included in this study. Animals in groups 1 and 6 were injected with citrate buffer, whereas rats in groups 2,3,4, and 5 received streptozotocin (STZ, 55 mg/kg iv in citrate buffer). Five days later animals in groups 4,5, and 6 received insulin (group 4) and subcutaneous implantation of slow-releasing pellets containing either the GC receptor blocker RU 486 (group 5) or a high dose of GC (group 6). MAIN OUTCOME MEASUREMENTS: Skin wound tensile strength and PVA sponge collagen metabolism were determined using tensiometric, spectrosphotometric, and polymerase chain reaction-based assays. In addition, cell infiltration and granulation tissue growth were assessed using a well-established histochemical technique. RESULTS: Wound-related parameters including fibroplasia, neovascularization, and inflammatory cell numbers were reduced as a function of diabetes. Similarly, skin wound tensile strength, PVA sponge hydroxyproline content, and the levels of mRNA transcripts for type I and III collagen were also decreased in this disease state. This diabetes-related deficit in wound healing potential was ameliorated by subjecting diabetic animals to insulin treatment or by counteracting the excessive actions of GCs using both pharmacological (RU 486) and endocrinological (ADX) paradigms. CONCLUSION: The current study supports the notion that GCs are implicated in the wound healing deficit of diabetics. Moreover, it illuminates the therapeutic potential of the GC receptor blocker (e. g., RU 486) in promoting wound repair under hypercortisolemic conditions including diabetes and Cushing's syndrome.

Musculoskeletal manifestations with panniculitis--a hospital based study on 62 patients in Kuwait.

The study describes 62 patients seen over a period of 4 years mainly presenting with an acute inflammatory ankle arthritis/periarthritis associated with panniculitis. Based upon the clinical characteristics of panniculitis two distinct categories could be defined. These included patients with characteristic lesions of erythema nodosum, seen in 51 (82%), the idiopathic form in 29 (57%), and secondary EN in 22 (43%). Associated conditions included Behçet's disease, oral contraceptive pills, pregnancy and penicillin treatment. Patients clinically not having typical EN was seen in 11 (18%). In this group the histopathology showed erythema induratum in 4, cutaneous-polyarteritis nodosa with minimal panniculitis in 3, Weber-Christian disease, cytophagic histiocytic panniculitis, and 'mixed' lobular and septal variety of panniculitis in 1 each. (In 1 patient the disease was not panniculitis but cutaneous variant of granuloma annulare). It is concluded that in a hospital setting EN associated with acute musculoskeletal symptoms, mainly ankle arthritis/periarthritis or an acute peripheral polyarthritis, was a common rheumatological problem in Kuwait. However, other forms of panniculitides also presented with musculoskeletal manifestations requiring accurate histopathological diagnosis for appropriate treatment.

Role of nuclear grooves in the diagnosis of papillary thyroid carcinoma. A quantitative assessment on fine needle aspiration smears.

Thirty-four cases of papillary thyroid carcinoma and 69 control cases consisting of 17 follicular neoplasms, 5 Hürthle cell neoplasms, 7 medullary carcinomas, 6 thyrotoxic goiters, 19 chronic lymphocytic thyroiditis cases, 3 subacute thyroiditis cases and 12 colloid goiter cases were studied for nuclear grooves. Such grooves were seen in 100% of papillary carcinoma and in 75-100% of other thyroid disorders, but their number was strikingly higher in papillary carcinoma. A quantitative assessment for nuclear grooves was made based on counting 500 follicular cells in hematoxylin and eosin (H&E)-stained and May-Grünwald-Giemsa (MGG)-stained smears. In H&E-stained smears of papillary carcinoma the number of cells with nuclear grooves (227.3 +/- 99.96 SD) was significantly higher as compared to other thyroid disorders (P < .01 to < .001). Eighty-eight percent of papillary carcinoma had nuclear grooves in > or = 20% tumor cells, whereas none of the other thyroid diseases exceeded this level. In MGG-stained smears the number of cells with nuclear grooves (40.7 +/- 32.83 SD) was also significantly higher as compared to other thyroid disorders (P < .05 to < .001). Of papillary carcinomas, 67.6% had > or = 4% cells with nuclear grooves, whereas 0-40% of other thyroid diseases exceeded this level. Nuclear grooves were significantly higher in H&E-stained smears of papillary carcinoma as compared to MGG-stained smears (P < .001). Based on this objective assessment, nuclear grooves were a useful criterion in the diagnosis of papillary thyroid carcinoma in H&E-stained smears but were not as reliable in MGG-stained smears.

Intranuclear Reinke's crystals in a testicular Leydig cell tumor diagnosed by aspiration cytology. A case report.

Fine needle aspiration cytologic findings in a Leydig cell tumor of the testis are described. Besides the rarity of case reports on fine needle aspiration cytologic diagnosis of this tumor, the present case was of interest because of the finding of numerous intranuclear and intracytoplasmic Reinke's crystals as well as some lying free between the cells. In a few cells the intranuclear crystals were seen to orient themselves in a row, with a nipplelike protrusion of the nuclear membrane as if being pushed by the crystals. Besides the well-formed crystals, many nuclei showed irregular, thin, groovelike spaces that may have been earlier stages of crystal formation. These findings suggested the intranuclear formation of Reinke's crystals. Extranuclear crystals were seen to fuse in pairs and hence to appear thicker than the intranuclear crystals. The crystals lying free between the cells also showed a linear arrangement in places. The crystals were more numerous with May-Grünwald-Giemsa (MGG) staining. Intranuclear crystals were seen only in MGG-stained smears.

Lymphoglandular bodies in lymphoid lesions and non-lymphoid round cell tumours: a quantitative assessment.

Lymphoglandular bodies (cytoplasmic fragments) were counted in 10 high power fields (HPF) of the smears in 35 cases of non-Hodgkin lymphoma (NHL), 26 Hodgkin's disease (HD), 36 reactive lymphadenitis, 24 non-lymphoid round cell tumors, and 20 cases of secondaries in lymph nodes. The number of lymphoglandular bodies in both May-Grünwald-Giemsa (MGG) and hematoxylin-eosin (H&E) stained smears in NHL, HD, and reactive lymphadenitis were significantly higher compared to non-lymphoid round cell tumors (P < 0.001). In H&E stained smear 92.5% of NHL, 86.2% of reactive lymph nodes, and 66.7% of HD cases had > 100 lymphoglandular bodies per 10 HPF. In MGG stained smears 100% NHL, 89.7% of reactive lymphadenitis, and 66.7% of HD cases contained > 100 lymphoglandular bodies per 10 HPF. On the other hand only 4.8% of non-lymphoid round cell tumors crossed this level in both H&E stained and MGG stained smears. Number of lymphoglandular bodies was also significantly higher in MGG stained smears compared to H&E stained smears (P < 0.05 to < 0.01) and in fine-needle aspiration (FNA) smears compared to imprint smears (P < 0.01 to < 0.001) in cases of NHL, HD, and reactive lymphadenitis.