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Right atrial (RA) dilatation may be important for patients' outcome in pulmonary arterial hypertension (PAH). The aim of this study was to examine the longitudinal RA and right ventricular (RV) remodelling in PAH patients using real-time three-dimensional echocardiography (3DE) and their relation to clinical outcome. Methods and results Sixty-two consecutive PAH patients were studied and compared with a control group of 30 healthy volunteers. RA and RV sphericity indices were measured with 3DE. RV ejection fraction (RVEF), RA volume (RAvol), and the quan- tification of jet area of tricuspid regurgitation (TR) were measured. Two observers were used for reproducibility as- sessment. The geometrical change of RA and RV was assessed in relation to clinical outcome, as defined by the increase of functional class or admission to the hospital due to right heart failure. Over 1 year of follow-up, there was significant increase of RA sphericity index (0.85+ 0.16 vs. 1.2+ 0.24, P , 0.01), RV dilatation (RV sphericity index 0.71+ 0.07 vs. 0.98+ 0.04, P , 0.01), as well as deterioration of RV systolic function (RVEF 33+ 8.2 vs. 28+ 7.6%, P , 0.01). Twenty-three patients (37%) had a clinical deterioration within 1 year. An increase of RA sphericity index .0.24 predicted clinical deterioration with a sensitivity of 96% and a specificity of 90% (area under the curve (AUC) 0.97). RV sphericity index was less sensitive (70%) and specific (62%) in predicting clinical deterioration (AUC 0.649). The deterioration in RVEF had a sensitivity of 91.1% and a specificity of 35.3% (AUC 0.479) in predicting clinical deterioration. The dilatation of RA .14 mL over 1 year had high sensitivity at 82.6% but low specificity at 30.8% in predicting clinical deterioration. Conclusion PAH leads to RA and RV dilatation and functional deterioration which are linked to an adverse clinical outcome. 3DE measurement of RA sphericity index may be a suitable index in predicting clinical deterioration of PAH patients.

Summary Aims Transitional cell metaplasia (TCM) of the cervix and vaginal vault is rarely reported. We sought to describe the clinical and cytological features and cytological differential diagnosis of TCM. Methods Cervical and vaginal vault smears reported as TCM or smears from patients with histologically confirmed TCM were examined for the following features: cellularity, architecture, background cell population, cell group thickness, cell shape, nuclear features (shape, chromatin, nucleoli, outline), perinuclear haloes, the presence in cell groups of a surface layer of cuboidal cells, and associated pathology. The cases of TCM were compared with smears of conventional atrophy and high grade squamous intraepithelial lesion (HSIL). Results Six cases (five cervical, one vaginal vault) of TCM were identified from six patients (age range 34–80 years, median 60 years). The smears showed three-dimensional cell groups (2–5 cells in thickness) composed of oval-shaped cells with small amounts of cytoplasm and spindle/ovalshaped nuclei, with the impression of ‘streaming’ in some groups. The nuclei showed mild membrane irregularities, evenly distributed chromatin, and small nucleoli. Nuclear grooves were identified in at least occasional cells in four cases. A surface layer of cuboidal cells was identified in two cases. The background contained dysplastic squamous cells in three cases. Atrophic changes were present and in one case some cell groups exhibited transition from TCM at one end to more conventional atrophic parabasal cells at the other. Conclusions Awareness of the cytological features of TCM is critical to avoid a false-positive diagnosis of HSIL, and the consequent ramifications for patients. TCM should always be considered in the differential diagnosis of multilayered cell groups in cervicovaginal smears, particularly in peri- and post-menopausal women and in atrophic conditions.

Background The use of fine needle biopsy (FNB) for the diagnosis of metastatic melanoma can lead to the early removal and treatment of metastases, reduce the frequency of unnecessary surgery, and facilitate the staging of patients enrolled in clinical trials of adjuvant therapies. In this study, the accuracy of FNB for the diagnosis of metastatic melanoma was investigated. Methods A retrospective cohort study was performed with 2204 consecutive FNBs performed on 1416 patients known or suspected to have metastatic melanoma. Almost three-quarters (1582) of these FNBs were verified by either histopathologic diagnosis following surgical resection or clinical follow-up. Results FNB for metastatic melanoma was found to have an overall sensitivity of 92.1% and a specificity of 99.2%, with 69 false-negative and 5 false-positive findings identified. The sensitivity of the procedure was found to be influenced by six factors. The use of immunostains, reporting of the specimen by a cytopathologist who had reported >500 cases, lesions located in the skin and subcutis, and patients with ulcerated primary melanomas were factors associated with a significant improvement in the sensitivity of the test. However, FNBs performed in masses located in lymph nodes of the axilla and FNBs that required more than one needle pass to obtain a sample were far more likely to result in false-negative results. Conclusions FNB is a rapid, accurate, and clinically useful technique for the assessment of disease status in patients with suspected metastatic melanoma.

Fine-needle biopsy (FNB) has been reported as a rapid, minimally invasive technique for the diagnosis of metastatic melanoma. The diagnostic accuracy of FNB was assessed in a consecutive series of 2,204 FNBs of clinically suspicious lesions from patients with previous primary melanomas treated at the Sydney Melanoma Unit, Sydney, Australia, between January 1992 and December 2002. The sensitivity and specificity of FNB were 96.3% and 98.9%, respectively. There were 5 false-positive cases (0.6%), which were verified as metastatic adenocarcinoma (3 cases) or reactive processes (organizing hematoma and chronic osteomyelitis, 1 each). False-negative diagnoses (6.7% of cases) were associated with a variety of clinicopathologic factors, including difficult-to-access anatomic sites (eg, high axilla or deep inguinal), small lesions, and lesional characteristics such as fibrosis, necrosis, or cystic change. FNB is a highly accurate, rapid, and cost-effective procedure for the diagnosis of metastatic melanoma and should be considered as the initial diagnostic procedure of choice in patients with melanoma with clinically suspected metastases. Melanoma is a common tumor, accounting for approximately 3% of all cancers. 1 It is a major cause of mortality and has a major impact on the most productive years of life because it is often diagnosed in relatively young people. 2 Survival in patients with melanoma is related to the stage of the disease at diagnosis, and patients with metastatic melanoma have much poorer survival than those without metastases. 3-7 Melanoma

Cryptococcus neoformans is an opportunistic fungal pathogen and an important cause of morbidity and mortality in immunocompromised patients. We report a case of osteomyelitis caused by C. neoformans in a liver transplant recipient who presented with a headache and scalp lump after sustaining mild head trauma. There was no evidence of central nervous system involvement or dissemination. This is the first known case report of isolated cryptococcal osteomyelitis in a liver transplant recipient.

Background: Apelin is an endogenous peptide of the APJ receptor that has physiological actions in the cardiovascular system and is abundantly expressed in the pulmonary vasculature. Pre-clinical models and preliminary clinical data indicate that apelin deficiency may mediate, or contribute to, the pathogenesis of pulmonary arterial hypertension (PAH). Apelin can modulate vasomotor tone and is one of the most potent endogenous inotropes yet described. Aims and objectives: We aimed to investigate the effects of apelin in patients with PAH and its effects on their pulmonary circulation. Methods: Twenty patients with PAH participated in a ranomised double-blind placebo-controlled study of apelin (10-100 nmol/min) and matched saline placebo infusions during right heart catheterisation. Mean pulmonary artery pressure, pulmonary artery wedge pressure and cardiac output were measured. Results: Apelin caused an increase in cardiac output (p

Fine-needle biopsy (FNB) is commonly used in the investigation of patients with a history of melanoma who present with possible metastatic disease. Non-melanoma malignancies (NMM) are common in the general population and not infrequent in patients with melanoma. Such tumors may be difficult to distinguish from metastatic melanoma on FNB. We sought to determine the types of NMMs that occur in melanoma patients, to document the frequency with which they were diagnosed by FNB, and to highlight potential pitfalls in cytologic diagnosis. NMMs occurring in 1416 consecutive melanoma patients who underwent FNB of 2204 clinically suspicious lesions between 1992 and 2002 at a single center were reviewed and analyzed. The sites of FNB included lymph nodes (36.9%), skin and subcutis (25.1%), visceral locations (17.9%), and other sites (20.0%). Of the 1416 melanoma patients investigated by FNB, 116 (8.2%) had a metachronous or synchronous NMM; the NMM was diagnosed by the FNB in 17 (14.7%) patients. The most common NMMs were epithelial tumors (69.4%, most commonly carcinomas of large bowel, breast and prostate) and hematologic malignancies (21.8%). As NMMs are not infrequent in patients with melanoma, they should always be considered in the differential diagnosis of clinically suspicious masses in patients with a history of melanoma, as well as in patients at high risk of melanoma. Careful assessment of the FNB cytologic features and directed use of ancillary studies should enable accurate diagnosis in most cases and facilitate appropriate patient management.

Aims: To describe the cytological appearances of melanoma in fluid specimens and potential diagnostic pitfalls in interpreting such specimens, which have been infrequently reported in the literature. Methods: Cases of melanoma diagnosed at a single institution between 1993 and 2008 in cytology specimens of fluids (pleural, ascitic, cerebrospinal and other fluids), but excluding fine needle biopsy specimens, were identified and reviewed. Results: 32 fluid specimens containing metastatic melanoma (from 26 patients) were identified. Most of the specimens were moderately cellular and showed moderate to marked nuclear pleomorphism. Mitotic figures and intranuclear cytoplasmic invaginations were identified in 11 (34.4%) and seven (21.9%) cases, respectively. Melanin pigment was seen in eight (25.0%) cases. Variable numbers of histiocytes were present, and mesothelial cells were present in body cavity fluid specimens. Conclusions: In fluid specimens, reactive mesothelial cells and histiocytes may mimic epithelioid melanoma cells. Awareness of the morphological features and diagnostic pitfalls of melanoma in fluids is necessary to avoid the potentially serious consequences of misdiagnosis.

Desmoplastic melanoma (DM) is a rare subtype of melanoma characterized by malignant spindle cells associated with prominent fibrocollagenous stroma. Primary melanomas may be entirely desmoplastic ("pure" DM) or exhibit a desmoplastic component admixed with a nondesmoplastic component ("combined" DM). The cytologic features of only 5 cases of DM have been reported previously. Fine-needle biopsy (FNB) specimens from 20 recurrent or metastatic lesions in patients with cutaneous DM and 20 recurrent or metastatic lesions from patients with primary cutaneous non-DM were examined and compared. FNB specimens of patients with DM were less cellular (P = .009) and less often exhibited intranuclear cytoplasmic invaginations (P = .008) and mitotic figures (P = .006) than specimens from patients with non-DM. "Combined" DMs were more commonly composed of epithelioid cells (P = .017) and less often contained bizarre/giant tumor cells (P = .010) than did "pure" DMs. Recurrent and metastatic DM has a range of cytologic appearances. Awareness of the cytologic features and careful clinicopathologic correlation will assist in accurate FNB diagnosis.

Background Fine-needle biopsy (FNB) diagnosis of metastatic carcinoma is based on cytological evaluation and ancillary investigations, e.g., immunocytochemistry. We present three cases which illustrate the utility of biochemical assay for tumour-specific markers as an aid to cytological diagnosis. Methods/Results Case 1 was a 68-year-old man with previously resected prostatic adenocarcinoma who presented with a neck mass. FNB yielded necrotic debris with scant viable atypical cells. The Hanks solution into which drops of FNB material had been deposited was centrifuged for cell block preparations, and biochemical assay for PSA on the fluid supernatant yielded a result of 7.9 μg/L. The elevated PSA was suggestive of metastatic prostatic adenocarcinoma, and this interpretation was confirmed histologically. Case 2 was a 30-year-old man with a past history of thyroidectomy for papillary thyroid carcinoma (PTC) who presented with two neck masses. FNB showed abnormal epithelial cells with features suggestive of PTC. Assay for thyroglobulin on Hanks solution supernatant yielded a value of 1163 μg/L (serum thyroglobulin 1.3 μg/L). This supported a diagnosis of metastatic PTC, which was subsequently confirmed in a histological specimen. Case 3 was a previously well 36-year-old man who presented with masses in the thyroid and neck lymph nodes. FNB showed a few atypical cells and amorphous extracellular material. Calcitonin level on the FNB supernatant (993 pg/mL) and serum calcitonin (1818 pg/mL) were elevated. A diagnosis of medullary thyroid carcinoma was made, and confirmed histologically. Conclusions Biochemical assay for tumour markers is a useful ancillary technique for assisting in FNB diagnosis of metastatic carcinoma, particularly when morphological assessment is compromised by low cellularity or cellular degeneration.

Aim The aim was to investigate a palpable lump in the right parotid region in a 67-year-old woman. Ultrasound showed a hypoechoic lesion of the right parotid gland (size 15 × 7 × 12 mm). Methods Fine needle aspiration (FNA) of the lump was performed. The ‘solid phase’ material was separated and homogenised using a Mini Beadbeater instrument then assayed on the Roche Hitachi Modular analyser. Results Cytology: the FNA showed crystalloid material that was of rectangular shape, non-birefringent and stained orange with Papanicolaou stain and blue with Diff-Quik stain. Biochemistry: The analyser ‘flagged’ amylase assay substrate depletion due to a very high amylase concentration giving a falsely low result that corrected with sample dilution. Discussion In this case both the cytology and the biochemical findings supported a finding of the amylase crystalloids in the parotid FNA sample. Although these crystalloids are not diagnostic they support a benign salivary gland lesion.

Congenital bronchopulmonary malformations detectable on prenatal ultrasound include cystic adenomatoid malformation (CAM), lobar sequestration, and upper airway atresia. We describe three fetuses with prenatally detected intrathoracic lesions in which the associated pulmonary hyperechogenicity disappeared before delivery. In the first case of pulmonary sequestration, the infant was asymptomatic after birth. However, in a case of CAM and another with laryngeal atresia, respiratory distress developed after delivery, despite recent scans showing apparently normal lung fields. This experience suggests that ultrasonic resolution of hyperechogenic lung lesions in utero does not necessarily indicate resolution of the underlying pathology.