Use of cytological samples of metastatic melanoma for ancillary studies.

OBJECTIVE: Fine needle aspiration (FNA) is widely used in the diagnosis of metastatic melanoma, both at initial presentation and in the setting of recurrent disease. The purpose of this study was to evaluate the performance of confirmatory immunohistochemistry (IHC) and molecular analysis of the BRAF mutation in cytological preparations of metastatic melanoma. METHODS: A 2-year retrospective review of pathology reports was performed on cytological samples of metastatic melanoma at the University Health Network (Toronto, Canada) and the Santa Casa Medical School (Sao Paulo, Brazil). IHC was performed on cell block sections prepared from formalin-fixed, fresh samples or residuum of CytoLyt/PreservCyt post-fixed in formalin. BRAF V600E/K mutations were assessed by amplification refractory mutation system (ARMS) analysis. RESULTS: A total of 104 samples (94 FNAs and 10 fluids) from 83 patients (20 women, 63 men) were included. IHC was attempted in 43 cases (41.3%) and successful in 41 (95.3%). The panel number of antibodies ranged from 1 to 15 (median 3). The most frequently used melanoma markers included HMB-45, melanoma cocktail and S100 protein, used in 25 (58.1%), 23 (53.5%) and 18 samples (41.9%). Thirty cases (69.8%) used three or fewer markers. The BRAF V600E/K mutation was tested in eight samples, being successful in seven (87.5%) and positive in three (37.5%). CONCLUSIONS: Cytological samples are a reliable and sufficient source for IHC and subsequent molecular analysis, allowing a reduced diagnostic time and rapid, appropriate treatment options in patients with advanced melanoma.

Epstein-Barr virus encoded RNA detected by in situ hybridization using cytological preparations.

OBJECTIVE: Detection of Epstein-Barr virus (EBV) status might help in the diagnosis of EBV-related neoplasms. The rate of successful assays for the detection of EBV-infected cells in cytological preparations has not been fully explored. Our aims were to examine the rate of successful in situ hybridization (ISH) assays for EBV-encoded RNA (EBER) in cytological specimens and to explore reasons for failure. METHODS: An electronic search selected cases with ISH-EBER assays performed on cytological preparations during a 10-year period. Data regarding patient age, gender and immune status, sample type and site, type of preparation, ISH-EBER results, immunophenotyping and immunohistochemistry results, final diagnosis and correspondent histopathological samples were retrieved. RESULTS: Sixty specimens from 58 patients with diagnoses of lymphoproliferative disorder (n = 35), carcinoma (n = 24) and sarcoma (n = 1) were identified. ISH-EBER assays were performed on 50 cell block sections and on 10 cytospin preparations, with 22 positive and 32 negative results. Six tests (four cytospins and two cell block sections) failed owing to loss of material during the assay and background staining, with an overall failure rate of 10% and 4% if cytospins were excluded. Assays were performed on 13 cytology and surgical specimens from the same site, with only one discrepant result. CONCLUSIONS: Cell block sections had more successful ISH-EBER assays when compared with cytospins. Reasons for failure were loss of material on the slide and background staining. A high concordance rate with surgical specimens emphasizes the usefulness of cytological samples for determining EBV status in patients with exhausted or no histological material available.

Cytomorphological and clinicopathological spectrum of pulmonary marginal zone lymphoma: the utility of immunophenotyping, PCR and FISH studies.

OBJECTIVE: To review cytomorphological criteria and clinicopathological findings in combination with ancillary tests for the specific diagnosis of pulmonary marginal zone lymphoma (MZL) in fine needle aspiration (FNA) specimens. METHODS: Cases of pulmonary MZL diagnosed using cytological specimens from 2005 to 2012 were retrieved and reviewed by three cytopathologists. Results of immunophenotypic analysis, interphase fluorescence in situ hybridization (FISH) and molecular assays were collated, together with clinical information and imaging data. Concurrent surgical biopsies were also retrieved. RESULTS: Fifteen lung FNA specimens were identified. The smears consisted predominantly of small centrocyte-like cells. Marked plasma cell differentiation was evident in 11 cases. All cases with slides available showed tissue fragments with lymphoid tangles (TFLTs). Multinucleated giant cells were present in nine cases, two of which showed granulomas. Immunophenotyping confirmed B-cell clonality in all cases. B-cell clonality was detected by polymerase chain reaction (PCR) in two samples. FISH identified MALT1 translocation in four of 10 cases tested and trisomy 3 in three of four cases. Concurrent surgical biopsies were diagnosed independently as MZL in seven cases. CONCLUSIONS: Cytology smears from lung FNA samples consisting of small lymphoid cells with a relative abundance of plasma cells or plasmacytoid cells and large TFLTs should prompt immunophenotyping and other ancillary studies, even if multinucleated giant cells and poorly formed granulomas are also identified. Specific diagnosis of pulmonary MZL in FNA samples can be rendered on the basis of morphological features coupled with the demonstration of B-cell clonality by immunophenotyping or PCR and cytogenetic abnormalities by FISH.

Fine-needle aspiration biopsy versus core-needle biopsy in diagnosing lung cancer: a systematic review.

BACKGROUND: Lung cancer leads cancer-related mortality in the world. The objective of the present systematic review was to compare fine-needle aspiration biopsy (fnab) with core-needle biopsy (cnb) for diagnostic characteristics and yields for diagnosing lung cancer in patients with lung lesions. METHODS: The medline and embase databases (from January 1, 1990, to September 14, 2009), the Cochrane Library (to Issue 4, 2009), and selected guideline Web sites were searched for relevant articles. RESULTS: For overall diagnostic characteristics (benign vs. malignant) of fnab and cnb, the ranges of sensitivity were 81.3%-90.8% and 85.7-97.4% respectively; of specificity, 75.4%-100.0% and 88.6%-100.0%; and of accuracy, 79.7%-91.8% and 89.0%-96.9%. For specific diagnostic characteristics of fnab and cnb (identifying the histologic subtype of malignancies or the specific benign diagnoses), the ranges of sensitivity were 56.3%-86.5% and 56.5-88.7% respectively; of specificity, 6.7%-57.1% and 52.4%-100.0%; and of accuracy, 40.4%-81.2% and 66.7%-93.2%. Compared with fnab, cnb did not result in a higher complication rate (pneumothorax or hemoptysis). No study has yet compared the diagnostic yields of fnab and of cnb for molecular predictive-marker studies in patients with lung lesions. DISCUSSION AND CONCLUSIONS: The evidence is currently insufficient to support a difference between fnab and cnb in identifying lung malignancies in patients with lung lesions. Compared with fnab, cnb might have a higher specificity to diagnose specific benign lesions. Well-designed, good-quality studies comparing fnab with cnb for diagnostic characteristics and yields in diagnosing lung cancer should be encouraged.

Assisting cytopathology training in medically under-resourced countries: defining the problems and establishing solutions.

Cytology is able to deliver rapid accurate diagnoses with minimal equipment and laboratory infrastructure at minimal cost, and this is especially so for fine needle biopsy (FNB), which is a powerful diagnostic tool in medically resource-poor environments, where histopathology laboratories are small in number and poorly supported financially. The crucial element in the development of cytology services is to train a sufficient number of well trained cytopathologists and cytotechnologists to create a 'critical mass' of personnel who not only provide routine diagnostic services, but also can train an ever expanding number of pathologists, cytotechnologists, and health workers. A review of practical programs to train cytopathologists and cytotechnologists in their own countries will be presented, including a recent series of FNB and cytology tutorials run in sub Saharan Africa. The need for local cytopathology programs and the potential for both local and visiting cytopathologists to provide a faculty will be discussed, as well as a range of possible programs which can bring African pathologists and trainee pathologists to Western institutions for periods of their training. Ideally, the regional Societies of Cytology, including the recently formed West African Society of Cytology, will establish their own diagnostic protocols, training programs, syllabuses, examinations and accreditation and career pathways for both cytopathologists and cytotechnologists, and organize tutorials where they will invite overseas faculty to contribute. Crucially, these new societies will empower cytopathologists and cytotechnologists to approach health services and governments to state the need for cytology services as a cost-effective accurate diagnostic service that enhances patient care.

Does confirmatory tumor biopsy alter the management of breast cancer patients with distant metastases?

BACKGROUND: Decisions about systemic treatment of women with metastatic breast cancer are often based on estrogen receptor (ER), progesterone receptor (PgR), and Her2 status of the primary tumor. This study prospectively investigated concordance in receptor status between primary tumor and distant metastases and assessed the impact of any discordance on patient management. MATERIALS AND METHODS: Biopsies of suspected metastatic lesions were obtained from patients and analyzed for ER/PgR and Her2. Receptor status was compared for metastases and primary tumors. Questionnaires were completed by the oncologist before and after biopsy to determine whether the biopsy results changed the treatment plan. RESULTS: Forty women were enrolled; 35 of them underwent biopsy, yielding 29 samples sufficient for analysis; 3/29 biopsies (10%) showed benign disease. Changes in hormone receptor status were observed in 40% (P = 0.003) and in Her2 status in 8% of women. Biopsy results led to a change of management in 20% of patients (P = 0.002). CONCLUSIONS: This prospective study demonstrates the presence of substantial discordance in receptor status between primary tumor and metastases, which led to altered management in 20% of cases. Tissue confirmation should be considered in patients with clinical or radiological suspicion of metastatic recurrence.

neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group.

PURPOSE: It remains a challenge to predict which women with axillary node-negative (ANN) breast cancer at greatest risk of relapse may benefit most from adjuvant therapy. Increases in neu/erbB-2 have been implicated in breast cancer prognosis. Although overexpression has been investigated extensively, this study represents the first prospective assessment of the prognostic value of neu/erbB-2 DNA amplification in a cohort of women with newly diagnosed ANN. METHODS: A consecutive series of women was monitored for recurrence (median follow-up duration, 36 months) and tumors from 580 individuals were analyzed for amplification. The association of amplification with risk of recurrence was examined in survival analyses with traditional and histologic markers as prognostic factors. RESULTS: Neu/erbB-2 was amplified in 20% of cases. We found an increased risk of disease recurrence when neu/erbB-2 was amplified > or = twofold that persisted with adjustment for other prognostic factors (relative risk, 2.36; P = .002). We found some evidence that amplification was more important in patients who received chemotherapy compared with untreated patients. CONCLUSION: neu/erbB-2 amplification is an independent prognostic factor for risk of recurrence in ANN breast cancer. Women with tumors without neu/erbB-2 amplification have a good prognosis; aggressive therapy in this group is therefore difficult to justify. On the other hand, even with adjuvant chemotherapeutic treatment, women whose tumors exhibit neu/erbB-2 amplification have an increased risk of recurrence. We encourage a randomized trial to compare more aggressive adjuvant chemotherapy versus standard chemotherapy for ANN women whose tumors exhibit neu/erbB-2 amplification.

Polyarteritis nodosa clinically masquerading as temporal arteritis with lymphadenopathy.

We describe a patient with biopsy proven polyarteritis nodosa who presented with headache, scalp tenderness and lymphadenopathy. This case illustrates the need to be wary of conditions mimicking temporal arteritis.

Infected thymic cyst: an unusual cause of respiratory distress in a child.

A 15-month-old male developed acute respiratory distress following a prolonged upper respiratory tract infection. Laboratory and radiological investigations suggested tracheal compression by a malignant anterior mediastinal mass. Following a short course of steroid therapy, urgent exploration of the mediastinum and resection of the mass was carried out; resolution of the airway obstruction was obtained. Histological and bacteriological examination of the lesion revealed it to be a thymic cyst infected by Haemophilus Influenzae with abscess formation. The causes of tracheal compression in childhood are discussed.

Q-fever. The liver and bone marrow pathology.

Eighteen liver and seven bone marrow biopsies from 44 patients with clinically and serologically proven Q-fever seen during a recent outbreak were studied. Highly distinctive fibrin-ring granulomas were found in seven liver and four bone marrow specimens. Lipid or nonspecific granulomas often containing neutrophils and variable numbers of giant cells were noted in 13 livers and seven bone marrows. A wide variety of nongranulomatous histological changes, frequently including steatosis and nonspecific "reactive" hepatitis, were seen in the liver biopsies. Identifiable rickettsiae were not present in tissue sections studied by microbiologic stains or electron microscopy. The histological response pattern to Coxiella infection is varied, and Q-fever should always enter the differential diagnosis of a granulomatous disease encountered in liver and bone marrow specimens.

Mineral oil lipogranulomata in liver and spleen. A study of 465 autopsies.

Lipogranulomata (LG) are commonly seen in human tissues but the location and significance of these lesions are incompletely documented. In a study of 465 autopsies LG were found in 48% of livers and 46% of spleens. Hepatic LG were more common in portal tracts than adjacent to the terminal hepatic venules. There was a close correlation between hepatic LG in liver and in spleen. The incidence and severity of hepatic LG were higher in older adults, especially men. There was no evidence that LG caused hepatic dysfunction or portal hypertension. The absence of correlation with hepatic steatosis supports the suggestion that LG are secondary to mineral oil deposition rather than to steatosis.

Medullary carcinoma of the thyroid in fine-needle aspiration biopsies.

A study of fine-needle aspiration biopsies (FNAB) in six cases of medullary carcinoma of thyroid (MCT) revealed that the presence of spindle cells in addition to the more usually recognized polygonal cells is a common feature and a significant clue to the diagnosis. Both spindle and polygonal cells contain cytoplasmic granules that stain positively for calcitonin by the immunoperoxidase technic. Amyloid, when present, can be identified presumptively in the Papanicolaou stain. This can be confirmed by restaining with Congo red. Both immunoperoxidase staining for calcitonin and amyloid staining for Congo red work well on the decolorized Papanicolaou-stained smears.