Michelle Reid-Nicholson

Calretinin immunostaining as an adjunct in the diagnosis of Hirschsprung disease

Historically, the diagnosis of Hirschsprung disease was made by evaluating multiple hematoxylin and eosin-stained slides and performing acetylcholinesterase histochemical staining. Recently, calretinin immunohistochemical staining has been reported and found to be superior to acetylcholinesterase staining in the confirmation of aganglionosis. We retrieved tissue blocks from 23 patients with proven Hirschsprung disease from the archives of the Medical College of Georgia. In addition, we selected 23 control patients with ganglion cells. All cases were stained with calretinin, and the presence or absence of both intrinsic nerve fibers (INFs) and ganglion cells was scored by 4 pathologists with fairly strong agreement (κ = 0.858). All cases of proven Hirschsprung disease were negative for INFs. Eighty-three percent of non-Hirschsprung patients were positive for INFs. Based on statistical analysis, the association between disease status and pathologist rating was statistically significant (P < .0001). We also found calretinin immunostaining to be a useful adjunctive modality in the diagnosis of Hirschsprung disease.

Cytologic features of mixed papillary carcinoma and chronic lymphocytic leukemia/small lymphocytic lymphoma of the thyroid gland

We report a case of papillary thyroid carcinoma (PTC) and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma of the thyroid gland. To the best of our knowledge, this is the first such case to be reported in the cytology literature. An 81‐year‐old male with known CLL presented for routine physical examination and was found to have a left‐sided thyroid nodule. Thyroid ultrasound showed a calcified nodule. Fine‐needle aspiration biopsy (FNAB) was performed and revealed PTC and an atypical lymphoid infiltrate that was suspicious for lymphoma. A partial thyroidectomy was performed and confirmed PTC with concurrent gland involvement by chronic lymphocytic leukemia/small lymphocytic lymphoma (SLL). Diagn. Cytopathol. 2008;36:813–817.

Fine needle aspiration findings in malignant ameloblastoma: A case report and differential diagnosis

We present a case of malignant ameloblastoma presenting in the posterior mandible and cervical lymph nodes of an African American child. This case is somewhat unusual in that the patient was an adolescent and presented with metastatic disease. This partly clinical as well as cytologic diagnosis was facilitated by the presence of typical ameloblastoma cytology in multiple cervical lymph nodes adjacent to the histologically confirmed intraosseous ameloblastoma. Although cytology is helpful in diagnosing ameloblastoma, its features are by no means definitive as there are several cytologic mimics. A high index of suspicion is therefore necessary to confirm or exclude ameloblastoma when evaluating any jaw lesion and/or adjacent enlarged lymph nodes by cytologic examination. Adequate sampling is paramount to accurate diagnosis, and is especially important when attempting to distinguish ameloblastoma from ameloblastic carcinoma. Diagn. Cytopathol. 2009.

Chromosomal abnormalities in renal cell carcinoma variants detected by Urovysion fluorescence in situ hybridization on paraffin-embedded tissue

Urovysion fluorescence in situ hybridization (UVFISH) identifies malignant cells in urine by detecting specific urothelial carcinoma-related chromosomal abnormalities. Some renal carcinomas (RCCs) share overlapping chromosomal aberrations with urothelial carcinoma. Malignant renal cells that are shed in urine can potentially cause a positive UVFISH result. We evaluated UVFISH in RCCs to determine its potential applicability to the diagnosis and grading of RCCs. Paraffin blocks from 39 RCCs (25 clear cell, 9 papillary, 2 chromophobe, and 3 sarcomatoid) and 15 controls (5 renal oncocytomas and 10 urothelial carcinomas) were tested. Of the RCCs, 15 (40%) were UVFISH-positive (9/25 [40%] clear cell, 3/9 [30%] papillary, 1/2 [50%] chromophobe, and 2/3 [67%] sarcomatoid carcinoma) and 24 (60%) were negative. Of the 15 controls, 8 (∼50%) were UVFISH-positive (2/5 [40%] oncocytomas and 6/10 [60%] urothelial carcinomas) and 7 (∼50%) were UVFISH-negative. Polysomy of chromosome 17 showed a statistically significant correlation with RCC subtype, being absent in most of the clear cell RCCs (P = .0096) compared with other RCCs. Polysomy of chromosome 7 was more frequent in high-grade than low-grade RCC (P = .0197) and more likely in high-grade clear cell than low-grade clear cell RCC (P = .0120). In conclusion, we showed that RCC has overlapping chromosomal abnormalities with urothelial carcinoma and can cause a positive UVFISH result. This has implications for the interpretation of Urovysion in patients whose urine contains malignant cells but who have negative cystoscopy and a concomitant renal mass. The chromosomal abnormalities observed in RCC are not distinct from those in urothelial carcinoma; therefore, UVFISH cannot distinguish these tumor types, nor can it type or grade RCC.

Granulosa cell tumor of the ovary: cytologic findings.

OBJECTIVE To describe the cytologic findings in 6 adult variants of granuloma cell tumors (AGCTs) and 1 juvenile variant (JGCT), emphasizing differences between recurrent/metastatic (REC AGCT) and nonrecurrent tumors (NED AGC7). STUDY DESIGN Imprints and fluids were evaluated for: hypercellularity, Call-Exner bodies (CEB), sheets, single cells/naked nuclei, nuclear grooves, single cell necrosis and established histologic criteria of atypia in AGCT (>3 mitoses, pleomorphism, hyperchromasia, prominent nucleoli). RESULTS All AGCTs and JGCT showed hypercellularity, clusters, sheets, single cells and naked nuclei. CEBs and grooves were seen only in AGCTs. Fluids had less cellularity than imprints, fewer clusters, grooves, single cells/naked nuclei and no sheets, CEBs, necrosis or vacuoles. Hyperchromasia and nucleoli were more striking in JGCT than AGCTs. All REC AGCTs had cytoplasmic vacuoles, while NED AGCTs did not. Prominent nucleoli were 3 times more common in REC AGCTs than NED AGCTs. Increased mitoses and necrosis were seen in 1 REC AGCT. CONCLUSION CEBs and grooves are not seen in JGCT. JGCT shows more striking cellular atypia than AGCT (REC AGCTs and NED AGCTs). When evaluating pelvic washes/ascitic fluid a high index of suspicion is necessary, as tumor cells can be overlooked. AGCTs showing cytoplasmic vacuoles, prominent nucleoli, mitoses and necrosis are suggestive of aggressive behavior, and that information should be conveyed in cytology reports.

The cytologic findings in choroid plexus carcinoma: Report of a case with differential diagnosis

Choroid plexus carcinoma is a rare tumor of the choroid plexus that shows frank cytologic features of malignancy including frequent mitoses, increased cellularity, nuclear pleomorphism, loss of papillary architecture, and necrosis. It occurs predominantly in the pediatric population and is associated with a poor prognosis. We report the cerebrospinal fluid and intraoperative squash preparation cytologic findings of a case of choroid plexus carcinoma arising in the lateral ventricle of a 16‐year‒old girl who developed tumor recurrence in cerebrospinal fluid 6 years after initial resection. To the best of our knowledge, there are only a few reports in the English literature describing the cytologic features of choroid plexus carcinoma. Relevant differentials and the usefulness of ancillary studies in diagnosis are also discussed. Diagn. Cytopathol. 2012.

Plasmablastic lymphoma with small lymphocytic lymphoma: Clinico-pathologic features, and review of the literature

Plasmablastic lymphoma (PBL) is currently considered as a rare subtype of diffuse large B-cell lymphoma (DLBCL) by the World Health Organisation (WHO) classification system [1]. PBL occurs mostly in human immunodeficiency virus (HIV) positive patients involving extranodal sites such as oral cavity [2–4]. PBL as a variant of Richter syndrome (RS) has been reported only in one patient with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) [5]. A 42-year-old man was referred to our institution with an outside diagnosis of anaplastic plasmacytoma. He presented with dyspnea, facial swelling, fever and night sweats. Physical examination revealed facial and neck swelling with massive collateral vessels around the chest wall and abdomen. There was no peripheral lymphadenopathy or organomegaly. The patient’s white blood cell count was 86 10/L with an absolute lymphocyte count of 26 10/L. There was no monoclonal spike in the serum or urine. Testing for HIV by p24 antigen immunoassay was negative. Cerebrospinal fluid (CSF) analysis was negative for malignant cells. A computed axial tomography scan of the chest revealed massive mediastinal lymphadenopathy occluding the superior vena cava (SVC). Magnetic resonance imaging of the brain was negative for leptomeningeal and parenchymal disease at the time of diagnosis. H&E-stained slides of the mediastinal biopsy revealed large, pleomorphic, lymphoid cells with irregular nuclear contours, vesicular chromatin, prominent nucleoli and abundant amphophilic cytoplasm. The tumor was mitotically active with extensive single cell necrosis. The typical nuclear and cytoplasmic features of a plasmacytoma were not present. The tumor showed features that were more consistent with a large cell lymphoma. Imprint preparation of the mass revealed distinct plasmacytoid morphology of the neoplastic cells. Immunohistochemical stains revealed that the neoplastic cells were positive for CD138 and MUM-1, and negative for CD3, CD5, CD20, CD79a CD10, CD23, CD30, CD43, leukocyte common antigen (LCA), CD45RO, BCL-1, BCL-2, PAX-5, BCL-6 and pancytokeratin. Human herpes virus 8 (HHV-8) was positive by immunostaining. Kappa and lambda immunostains were equivocal. Epstein Barr virus (EBV)-encoded RNA (EBER) in-situ hybridisation was negative. The morphologic and immunophenotypic findings were consistent with PBL rather than anaplastic plasmacytoma. Bone marrow (BM) biopsies performed at both our institution and the referring institution revealed involvement by large atypical lymphoid cells similar to those seen in mediastinal biopsy (Figure 1a). These neoplastic cells had the same immunophenotype as the mediastinal mass and also demonstrated unequivocal lambda light chain restriction. There was no evidence of BM plasmacytosis. Additionally, both biopsies showed a separate lymphoid aggregate composed of small uniform lymphocytes (Figure 1b) that co-expressed CD20 and CD5 and were negative

Interobserver and intraobserver variability in the calculation of the lipid-laden macrophage index: Implications for its use in the evaluation of aspiration in children

The lipid‐laden macrophage index (LLMI) is a semiquantitative test used to evaluate aspiration in children. We assessed the reliability and reproducibility of LLMI by calculating interobserver and intraobserver variability among pathologists, with and without expertise in cytopathology. Forty‐nine bronchoalveolar washes/lavages were blindly reviewed by four reviewers and assigned an LLMI. Three pathologists (two cytopathologists, one pathology fellow) reviewed slides twice and one cytotechnologist reviewed them once. Intraclass correlation coefficient (ICC) with 95% confidence interval (C.I.) was used to measure overall intraobserver and interobserver agreement. Interobserver agreement was also calculated separately for each pair of reviewers. ICC values did not indicate an acceptable level of interobserver agreement among pathologists, with (ICC = 0.67, 95% C.I.: 0.56–0.77) and without (ICC = 0.77, 95% C.I.: 0.61–0.84) the cytotechnologist included in the analysis. An ICC of 0.84 (95% C.I.: 0.78–0.89) indicated an acceptable level of intraobserver agreement among pathologists. When calculated separately for each pair of reviewers, all but two ICC values for interobserver agreement were less than 0.75 (the minimally acceptable value for a reliable clinical measurement), and the lower confidence limit of each of the 95% C.I. was far below the 0.75 cutoff. Using Lins coefficient, intraobserver variability was only acceptable for two pathologists. Our study highlights the lack of precision and subjectivity of the LLMI, as well as the significant inter and intraobserver bias that may occur among experienced and inexperienced pathologists, and cytotechnologists. Clinicians and cytopathologists alike should be mindful of this potential pitfall and interpret LLMI scores with caution. Diagn. Cytopathol. 2010;38:861–865.

Imprint cytology of high‐grade immature ovarian teratoma: A case report, literature review, and distinction from other ovarian small round cell tumors

Immature ovarian teratoma (IOT) is a rare and aggressive malignant neoplasm characterized by immature neural tissue. The cytomorphologic features have only rarely been described. We herein describe an additional case and review the literature regarding this entity. To the best of our knowledge, this is the first reported case with imprint cytology. A 35‐year‐old woman presented with a pelvic mass which was resected and sent for frozen section evaluation. Imprint smears and frozen section of the mass were diagnostic of IOT. IOT has diagnostic cytologic features which show complete concordance with histology. Differential diagnoses include other small round cell neoplasms such as ovarian neuroblastoma, small cell carcinoma of hypercalcemic type, primitive neuroectodermal tumor, Wilms tumor, desmoplastic small round cell tumor, and Non‐Hodgkin lymphoma. Distinguishing IOT from these tumors can be challenging however if diligent morphologic study and/or ancillary studies are performed accurate diagnosis is possible. Diagn. Cytopathol. 2008; 36: 595–599.

Fine needle aspiration cytology of an endotracheal mass report of a case with an unusual presentation of anaplastic large cell lymphoma

BACKGROUND Anaplastic large cell lymphoma (ALCL) is an uncommon hematolymphoid neoplasm characterized by malignant lymphocytes of T-cell phenotype. It usually affects young patients and may involve a variety of tissues and organs. We herein describe a case of ALCL that presented as an endotracheal mass with associated hilar lymphadenopathy. To the best of our knowledge this is the first case in the literature arising in the trachea. In this location the diagnosis of ALCL can be especially difficult as its pleomorphic cytomorphology mimics that of a carcinoma, which is a more typical neoplasm arising in the trachea. CASE A 26-year-old male presented with hemoptysis and paroxysmal chest pain. Imaging revealed an endotracheal mass and multiple lytic bone lesions. Fine needle aspiration biopsy of the endotracheal mass revealed discohesive malignant cells with abundant, pale cytoplasm and cerebriform, donut-shaped and horseshoe-shaped nuclei. Immunohistochemical studies confirmed the diagnosis of ALCL. CONCLUSION ALCL may have an unusual presentation and involve diverse sites, including the trachea. While its cytologic features are straightforward, a high index of suspicion is necessary to ensure accurate diagnosis when it presents in unusual locations.