Nancy P. Caraway

Strategies to diagnose lymphoproliferative disorders by fine-needle aspiration by using ancillary studies

Received July 7, 2005; revision received July 22, 2005; accepted July 25, 2005. A multiparameter approach is key to diagnosing lymphoproliferative disorders by fine-needle aspiration (FNA) biopsy. In this approach, the cytomorphologic features of the lymphoid population are analyzed in conjunction with ancillary studies such as immunophenotyping, ploidy analysis, cytogenetics, and molecular studies. This is not a new concept but one that has been used successfully for many years, especially in Europe. It does, however, take more time, effort, and technical support than the typical FNA procedure. At The University of Texas M. D. Anderson Cancer Center we have been diagnosing lymphomas by using a multiparameter approach for over 15 years. –12 Of course, it has been refined and additional ancillary studies have been incorporated. Over the past 10 years, numerous institutions worldwide have reported FNA studies to show relatively high sensitivity and specificity in the diagnosis of lymphomas when used in conjunction with ancillary studies. Despite this, the use of FNA biopsies to diagnose lymphomas remains controversial. This article outlines our institution’s multiparameter approach to diagnosing lymphoproliferative disorders by FNA. B-cell lymphoma is the most common type of lymphoma in the U.S. and, therefore, this article will focus primarily on them. Some of the T-cell and Hodgkin lymphomas will also be addressed, but this is not intended to be a comprehensive review of all lymphoproliferative disorders. The terminology in this article comes from the World Health Organization’s (WHO) classification of tumors of the hematopoietic and lymphoid tissues, which is based on their cytomorphologic, immunophenotypic, and cytogenetic features; these criteria can be readily applied to cytologic specimens. An important step in FNA biopsy is to immediately assess the aspirated material to confirm that it is optimal cytologically and sufficient for ancillary studies. It is not uncommon to perform three or four FNA biopsies per site. This is usually tolerated well by patients. To confirm that the material is adequate, a small drop of the aspirated material is smeared onto the slides. Next, the slides are air-dried and alcohol-fixed and then stained with the Diff-Quik (Harleco, Gibbstown, NJ) and Papanicolaou methods. The Diff-Quik method highlights cytoplasmic features, while the Papanicolaou method is optimal for analyzing nuclear features. The remaining material is rinsed in a cell preservative such as RPMI-1640 (Roswell Park, Buffalo, NY). At our institution, we try to collect at least 10 million cells that can be quantified by using an automated counter (Coulter Electronics, Hialeah, FL). This usually provides enough material for immunophenotyping, and in most instances it is enough for other ancillary studies as well. 432 CANCER CYTOPATHOLOGY

Use of fine‐needle aspiration biopsy in the evaluation of splenic lesions in a cancer center

Fine‐needle aspiration biopsy (FNAB) of the spleen was performed on 50 patients, of whom 40 had had a previous diagnosis of malignancy (23 lymphoproliferative disorders, 13 carcinomas, 3 melanomas, and 1 sarcoma). The cytologic diagnoses included 22 cases positive for malignancy (10 lymphomas, 9 metastatic carcinomas, 2 metastatic melanomas, and 1 sarcoma), 18 cases negative for malignancy, 4 cases suspicious for malignancy, and 6 nondiagnostic specimens. No major complications were associated with the FNAB procedure; however, one patient did develop a pneumothorax that resolved spontaneously. Subsequent splenectomy was performed in 10 of the 50 cases. There were no false‐positive diagnoses, and only one false‐negative diagnosis, which was attributed to sampling error. The aspirate, showing only benign splenic parenchyma, was from a patient with splenomegaly and no previous diagnosis; subsequent splenectomy showed acute myelogenous leukemia. In our study, FNAB proved to be a safe and valuable diagnostic tool for evaluating splenic lesions in oncologic patients. Diagn. Cytopathol. 16:312–316, 1997.

The utility of interphase fluorescence in situ hybridization for the detection of the translocation t(11;14)(q13;q32) in the diagnosis of mantle cell lymphoma on fine-needle aspiration specimens

Mantle cell lymphoma can be difficult to differentiate cytologically from other small cell non‐Hodgkin lymphomas. Nevertheless, the distinction is important, because mantle cell lymphoma is more aggressive than other small cell non‐Hodgkin lymphomas. The purpose of this study was to determine whether fluorescence in situ hybridization (FISH) is helpful in diagnosing mantle cell lymphoma on fine‐needle aspiration (FNA) specimens by detecting the t(11;14)(q13;q32) translocation that is characteristic of this tumor.

Ultrasound‐guided fine‐needle aspiration biopsy of the thyroid bed

Ultrasound (US) has been shown to be a sensitive technique for monitoring patients for recurrent thyroid carcinoma in the thyroid bed after total thyroidectomy. However, the role of US‐guided fine‐needle aspiration biopsy (FNAB) in the confirmation of sonographically indeterminate or suspicious masses has not been adequately addressed. The purposes of this study were to determine the sensitivity and specificity of US‐guided FNAB of the thyroid bed for diagnosing recurrent carcinoma after total thyroidectomy and to highlight potential diagnostic pitfalls.

Comparison of molecular abnormalities in bronchial brushings and tumor touch preparations: Potential use of fluorescence in situ hybridization to identify predictive markers in early-stage lung carcinomas

Preneoplastic lung lesions and early‐stage lung carcinomas are associated with molecular abnormalities. The authors performed a pilot study to evaluate the use of DNA fluorescence in situ hybridization (FISH) probes to ascertain whether these biomarkers can predict nonsmall cell lung carcinoma (NSCLC).

Fine-needle aspiration biopsy of metastatic small cell carcinoma from extrapulmonary sites

Like a pulmonary counterpart, extrapulmonary small cell carcinoma (SCC) is an aggressive tumor with a high rate of metastasis. Forty‐nine fine‐needle aspiration biopsies (FNABs) (36 patients) of various primary sites other than the lung diagnosed as metastatic SCC (including Merkel cell carcinoma) were reviewed. FNABs were derived from lymph nodes (20), liver (7), bone (2), breast (1), pancreas (1), and skin/soft tissue (18). Primary tumor sites included the prostate (14), skin (11; Merkel cell carcinoma), cervix (5), urinary bladder (3), urethra (1), ovary (1), and parotid (1). Aspirates revealed predominantly dispersed single tumor cells with occasional clustering. Tumor cells were small with scant cytoplasm, fine powdery chromatin, and inconspicuous nucleoli. Nuclear molding, mitotic figures, and apoptotic bodies were frequently observed. In four cases, findings from the FNABs were used to render the initial diagnosis of SCC. FNAB is useful for determining whether metastases contain a SCC component, a finding that may alter clinical management. Cytologically, SCC from different primary sites cannot be differentiated, and its distinction requires clinical and radiographic correlation. Diagn. Cytopathol. 1998;19:177–181.

Blastic variant of mantle-cell lymphoma: Cytomorphologic, immunocytochemical, and molecular genetic features of tissue obtained by fine-needle aspiration biopsy

Mantle‐cell lymphoma (MCL) is a rare type of non‐Hodgkins lymphoma that has a moderately aggressive clinical course, generally between that of low‐grade and of intermediate‐grade lymphomas. However, a small subset of MCLs, the so‐called “blastic” variant, exhibits a poor prognosis and an aggressive clinical course. We describe a case of blastic MCL that occurred in a 64‐yr‐old man and that was diagnosed and accurately subclassified as blastic MCL on the basis of a fine‐needle aspiration (FNA) biopsy. The aspirate smears showed a monotonous population of intermediate‐sized lymphocytes with irregular nuclear contours, finely dispersed nuclear chromatin, and inconspicuous nucleoli. Material was obtained by FNA for ancillary studies (immunocytochemical stains, flow cytometry, cytogenetics, image analysis, and molecular studies) that supported the diagnosis of blastic MCL. Surgical biopsy confirmed the diagnosis. These findings underscore the utility of FNA in diagnosing lymphomas, particularly when the cytomorphologic examination is combined with appropriate ancillary studies. Diagn. Cytopathol. 1998;19:59–62.

Cytologic features of renal medullary carcinoma: A study of three cases

Renal medullary carcinoma is a rare tumor that is most common in young black men with sickle cell disease or trait. Patients often present with advanced disease at the time of diagnosis, and their prognosis is poor, even with aggressive therapy. The clinical and pathologic features of renal medullary carcinoma have been described in several articles, but reports describing the cytologic features are rare.

Poorly-differentiated adenoid cystic carcinoma: cytologic appearance in fine-needle aspirates of distant metastases.

Adenoid cystic carcinoma (ACC) is a primary salivary‐gland neoplasm which typically yields characteristic cytomorphology upon fine‐needle aspiration (FNA). We report on the FNA findings of a case of ACC metastatic to the liver which demonstrated a predominantly solid, poorly‐differentiated pattern, an unusual but well‐recognized subtype associated with a poor clinical outcome. The FNA findings in 7 additional cases of ACC metastatic to distant sites were also reviewed, with 4 cases displaying a prominent poorly‐differentiated component. These findings suggest that, although not commonly recognized in salivary‐gland FNAs, the poorly‐differentiated pattern of ACC does occur in metastatic deposits and should be recognized as such, thereby preventing a needless search for a second primary malignancy. Diagn Cytopathol 1996;15: 296–300.

FNA of thyroid granular cell tumor

Granular cell tumor rarely occurs in the thyroid. This case report describes the cytologic features of a granular cell tumor seen in a fine needle aspirate obtained from a 27‐year‐old woman with a gradually enlarging thyroid nodule. The aspirate showed single as well as syncytial clusters of cells with abundant granular cytoplasm. The differential diagnosis in this case included granular cell tumor, Hurthle cell lesion/neoplasm, and a histiocytic reparative process. Immunohistochemical studies, including S‐100 protein and CD68, performed on a cell block preparation were helpful in supporting the diagnosis. Diagn. Cytopathol. 2013;41:825–828.