S. R. Mathur

Cell blocks in cytopathology: a review of preparative methods, utility in diagnosis and role in ancillary studies

The cell block (CB) is a routine procedure in cytopathology that has gained importance because of its pivotal role in diagnosis and ancillary studies. There is no precise review in the published literature that deals with the various methods of preparation of CB, its utility in diagnosis, immunocytochemistry (ICC) or molecular testing, and its drawbacks. An extensive literature search on CB in cytology using internet search engines was performed for this review employing the following keywords: cell block, cytoblock, cytology, cytopathology, methods, preparation, fixatives, diagnostic yield, ancillary and molecular studies. Ever since its introduction more than a century ago, the CB technique has undergone numerous modifications to improve the quality of the procedure; however, the overall principle remains the same in each method. CBs can be prepared from virtually all varieties of cytological samples. In todays era of personalized medicine, cytological specimens, including CBs, augment the utility of cytological samples in analysing the molecular alterations as effectively as surgical biopsies or resection specimens. With the availability of molecular targeted therapy for many cancers, a large number of recent studies have used cytological material or CBs for molecular characterization. The various techniques of CB preparation with different fixatives, their advantages and limitations, and issues of diagnostic yield are discussed in this review.

Neo-adjuvant chemotherapy in the treatment of advanced malignant germ cell tumors of ovary.

OBJECTIVE In order to preserve fertility, we attempted neo-adjuvant chemotherapy (NACT) in patients of malignant ovarian germ cell tumor (MOGCT) with advance and bulky disease. PATIENTS AND METHODS Between January 1988 and December 2009, 23 patients received NACT. Patients median age was 19 years, ranging from 14 to 28 years. FIGO stages III - 20 and IV - 3. Histology subtypes were: dysgerminoma, n = 14, mixed GCT, n=6 and 3 had endodermal sinus tumor. Patients were planned for four cycles of BEP (bleomycin, etoposide and cisplatin) chemotherapy followed by fertility sparing surgery (unilateral salpingo-oophorectomy+omentectomy ± lymphadenectomy). RESULTS Following NACT - 21 patients responded; complete (CR) - 16 and partial response (PR) - 5. One patient progressed and another was lost to follow-up after 2 cycles. 18 of 21 responders underwent surgery; 13/18 had pathological CR, 5/18 had residual disease and achieved CR following 2 more cycles of BEP. 3 patients refused for surgery; 2 relapsed at 9 and 12 months, and achieved second CR following salvage chemotherapy and surgery, third patient continues to be disease-free. Currently, 21 of 23 patients are alive and disease-free at a median follow-up of 74 months. 18/21 patients have resumed menstruation and 10 eligible patients have delivered 13 full term healthy babies. These results are comparable to patients with advanced disease (n = 43) treated with standard approach (initial surgery and adjuvant chemotherapy) during the same period. CONCLUSION NACT followed by fertility sparing surgery could be a reasonable option for patients of advanced MOGCT, not suitable for optimal cyto-reduction.

Utility and pattern of positivity of p40 in the diagnosis of squamous cell carcinoma of the lung by cytology: the first study on fine needle aspiration smears

Immunohistochemistry for p40 has emerged as a clinically applicable tool with high sensitivity and specificity to distinguish lung adenocarcinoma and squamous cell carcinoma (SCC). It appears to be an excellent marker for squamous differentiation. Although application of p40 in cell blocks has been reported, its expression has not been described in cytology smears. The aim was to study the expression of p40 in fine needle aspirates of SCC of the lung and to analyse differences in immunoreactivity in variably differentiated SCC.

An institutional experience with The Paris System: A paradigm shift from ambiguous terminology to more objective criteria for reporting urine cytology

Urine cytology is a highly specific modality for diagnosing high‐grade urothelial carcinoma (HGUC), but plagued by low sensitivity and wide inter‐observer variability mainly ascribed to the lack of an established template of reporting. The Paris System (TPS) working group proposed such a template at the 2013 International Congress of Cytology, replete with objective criteria for categorising specimens into one of the seven categories: non‐diagnostic, negative for HGUC, atypical urothelial cells, suspicious for HGUC, HGUC, low‐grade urothelial neoplasm and others (including non‐malignant entities). This study was undertaken to determine the impact of TPS criteria in the morphological interpretation of urine samples.

Utility of conventional transbronchial needle aspiration with rapid on-site evaluation (c-TBNA-ROSE) at a tertiary care center with endobronchial ultrasound (EBUS) facility

Background: Conventional transbronchial needle aspiration (c-TBNA) is an underutilized bronchoscopic modality. Endobronchial ultrasound (EBUS) guided-TBNA though efficacious is an expensive modality, facilities of which are available at only limited centers. c-TBNA is cost-effective and has potential for wide utilization especially in resource-limited settings. Rapid on-site evaluation (ROSE) improves the yield of c-TBNA. Materials and Methods: A retrospective review of the bronchoscopy records (May 2012 to July 2014) was performed. The patients who underwent c-TBNA with ROSE were included in the study and their clinical details were extracted. Convex probe EBUS-TBNA was being regularly performed during the study period by the operators performing c-TBNA. Results: c-TBNA with ROSE was performed in 41 patients with mean age of 42.4 (16.2) years. The most frequently sampled node stations (>90% patients) were the subcarinal and lower right paratracheal. Representative samples could be obtained in 33 out of the 41 patients (80.4%). c-TBNA was diagnostic in 32 [tuberculosis (TB)-8, sarcoidosis-9, and malignancy-15] patients out of the 41 patients. The overall diagnostic yield (sensitivity) of c-TBNA with ROSE was 78%. Mean procedure duration was 18.4 (3.1) min and there were no procedural complications. Conclusion: c-TBNA with ROSE is a safe, efficacious, and cost-effective bronchoscopic modality. When it was performed by operators routinely performing EBUS-TBNA, diagnostic yields similar to that of EBUS-TBNA can be obtained. Even at the centers where EBUS facilities are available, c-TBNA should be routinely performed.

Cytomorphology of neuroendocrine tumours of the gallbladder

Gallbladder neuroendocrine tumours (GB‐NETs) are rare and account for 0.5% of all NETs. GB‐NETs have an aggressive behaviour, which depends on the tumour grade. The cytomorphological spectrum of these tumours has never been described in detail. The present study evaluates the cytological features of GB‐NETs and grades them according to the World Health Organization (WHO) classification. Furthermore, the expression of thyroid transcription factor‐1 (TTF‐1) has not been investigated previously in GB‐NETs, although found in a subset of extrapulmonary NETs.

Fine needle aspiration cytology features of poorly differentiated thyroid carcinoma

Poorly differentiated thyroid carcinoma (PDTC) is an uncommon thyroid malignancy with biological behaviour intermediate between well‐differentiated and undifferentiated thyroid carcinoma. The cytological diagnosis of PDTC is often difficult as a result of a lack of well‐established cytomorphological features and a considerable degree of morphological overlap with other commoner thyroid neoplasms.

Primary Langerhans cell histiocytosis of the thyroid gland: role of langerin in FNA cytological diagnosis

cal data from the patients. For clinicians, we believe that our conclusion would add doubt concerning the value of RLUs. Therefore, we referenced the studies of Bae et al. and Castle et al. to explain the role of RLUs. Bae et al. reported that patients with high RLU/ CO values have a low negative conversion rate compared with patients with low RLU/CO cases. Castle et al. demonstrated that a positive hrHPV test identifies not only prevalent CIN but also the persistence of HPV infections and future disease developments. Thus, we suggest that a significant correlation with the severity of cervical lesions but a large overlap of viral loads between CIN grades could be as a result of the characteristics of the HPV viral loads. In conclusion, HPV viral loads expressed as RLU values are a very important predictor of the severity of cervical lesions in patients with ASC-US. However, RLU values should not be considered a diagnostic tool of cervical disease for patients. To determine more accurate cut-off values, a longerterm follow-up and investigating newly detected patients with cervical disease is needed.

Differentiation of histoplasma and cryptococcus in cytology smears: a diagnostic dilemma in severely necrotic cases

The correct identification of fungal organisms is important for the appropriate clinical management of patients. It becomes difficult in necrotic smears when the tissue response is not clearly discernible. It is difficult to distinguish between histoplasma and cryptococcus in severely necrotic cases, where both appear as variably sized clear refractile haloes.

Papillary cystadenoma of the epididymis associated with von Hippel-Lindau disease diagnosed on fine needle aspiration cytology.

after surgery. Thymic neoplasms constitute only 4% of mediastinal tumours in children and only 2–9% of these are thymolipomas. Fewer than 50 paediatric cases of thymolipoma have been reported to date in the available English literature. Thymolipoma was first reported by Lange in 1916 as a lipoma of the thymus. In 1948, Hall coined the term ‘thymolipoma’ for this tumour. The majority of patients are asymptomatic and the tumour is detected incidentally. However, respiratory symptoms have been reported in up to 50% of patients with thymolipoma, and a few cases have been reported in association with myasthenia gravis, aplastic anaemia, Graves’ disease, lymphoma and systemic lupus erythematosus. All thymolipomas occur in the anterior mediastinum and usually grow slowly, reaching a large size before diagnosis. Plain radiographs of thymolipoma can simulate cardiomegaly or other conditions, such as pericardial effusion and tumours. A pre-operative chest CT is helpful in diagnosis by the presence of characteristic fatty tissue containing soft tissue streaks that may represent islands of normal thymic component. Fat in the mediastinum can also be seen in lipoma, liposarcoma, teratoma, epicardial fat prominence or congenital diaphragmatic hernia. Although the diagnosis of thymolipoma is strongly suggested on imaging studies showing fat and soft tissue without local invasion, an exact diagnosis cannot be made. Fine needle aspiration cytology under imaging guidance is currently a favoured diagnostic modality for mediastinal masses because of the technical ease and minimally invasive nature of the technique. An extensive literature search yielded only two cytological reports of thymolipoma, one of which was misdiagnosed as liposarcoma on FNA. In our patient, a pre-operative FNA showed a population of mature lymphocytes together with a few epithelial cells, suggestive of thymic tissue. Although adipose tissue was not seen in the smears, a correlation with the radiological features suggested a diagnosis of thymolipoma and ruled out a possibility of teratoma. Surgical resection is the curative treatment of thymolipoma, most commonly via a sternotomy. On histological examination, thymolipoma is composed of elements of mesodermal (fat) and endodermal (thymic epithelium) origin. The tumour is usually well encapsulated and lobulated without any infiltration of adjacent structures. A few cases may demonstrate areas of calcification and cystic degeneration of Hassall’s corpuscles. In conclusion, this case is being presented for multiple reasons, including the rarity of the lesion and the probability of this tumour being encountered by cytopathologists, who need to be aware of this intriguing and unusual tumour, and should remember to follow the paradigm of clinical and radiological correlation.