Claudia Jones

Fine-Needle Aspiration in Non-Hodgkin Lymphoma Evaluation of Cell Size by Cytomorphology and Flow Cytometry

We studied 48 non-Hodgkin lymphoma (NHL) fine-needle aspiration (FNA) specimens with initial cytomorphology (CM) and flow cytometry (FC) and subsequent surgical biopsy of the same lesion to determine whether a reliable diagnosis of large cell lymphoma or large cell transformation could be made. CM was evaluated by examining 200 lymphocytes in each specimen. FC was performed by analyzing monoclonal or abnormal B-cell populations. Percentages of large cells were evaluated by CM and FC and results correlated with the histologic diagnosis. All small cell NHLs showed fewer than 40% large cells by CM and FC; 100% (9/9; FC) and 67% (6/9; CM) of diffuse large B-cell lymphomas demonstrated greater than 40% large cells. Variable numbers of large cells were detected in grade III follicular lymphoma, low-grade lymphoma with partial large cell transformation, and large B-cell lymphoma containing fewer than 10% neoplastic cells. By using combined CM and FC, large cell lymphoma and large cell transformation can be diagnosed reliably by FNA if greater than 40% large cells are present. Surgical biopsy is necessary when there is necrosis, fewer than 10% neoplastic cells by FC, or fewer than 40% large cells with clinical signs of transformation.

The Value of Fluorescence In Situ Hybridization and Polymerase Chain Reaction in the Diagnosis of B-Cell Non-Hodgkin Lymphoma by Fine-Needle Aspiration

CONTEXT Molecular genetic analyses have been predicted to improve the diagnostic accuracy of fine-needle aspiration of B-cell non-Hodgkin lymphoma. OBJECTIVE To determine the value of routine molecular genetic assays, polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH), in the diagnosis of B-cell non-Hodgkin lymphoma by fine-needle aspiration (FNA). DESIGN A multiparametric method, including cytology, flow cytometry, PCR, and FISH, was prospectively evaluated in the diagnosis of B-cell non-Hodgkin lymphoma by FNA. Aspirates from 30 consecutive patients with suspected hematolymphoid malignancies were collected. All aspirates were triaged through a uniform program including cell-size analysis, B- and T-cell clonality studies, flow cytometric immunophenotyping, and bcl-1 and bcl-2 gene rearrangements by PCR and FISH. After completion of FNA evaluations, FNA results were compared with diagnoses from prior or subsequent surgical biopsies. RESULTS Monoclonal B-cell populations were detected in 18 of 20 B-cell non-Hodgkin lymphomas by flow cytometry and PCR. bcl-1 gene rearrangement was detected in 2 of 2 cases of mantle cell lymphoma. bcl-2 rearrangement was detected in 5 cases including 4 of 4 low-grade follicular lymphomas and 1 transformed follicular lymphoma. By incorporating the results of molecular genetic and ancillary diagnostics, a definitive classification was reached in 12 cases of B-cell non-Hodgkin lymphoma by FNA, including all cases of low-grade follicular lymphoma (4/4) and mantle cell lymphoma (2/2) and approximately 50% of small lymphocytic lymphoma (2/4) and large B-cell lymphoma (4/8). Ten of the 12 cases with a final classification reached by FNA had either prior or follow-up surgical biopsies, and all 10 cases showed agreement between the diagnoses rendered on FNA and surgical biopsies. CONCLUSIONS With proper handling and management of specimens, FNA can routinely provide samples adequate for molecular genetic studies, in addition to cytomorphology and flow cytometry, making it possible to consistently render accurate and definitive diagnoses in a subset of B-cell non-Hodgkin lymphomas. By incorporating FISH and PCR methods, FNA may assume an expanded role for the primary diagnosis of B-cell non-Hodgkin lymphoma.

Primary pancreatic lymphoma evaluated by fine-needle aspiration: Findings in 14 cases

Fine-needle aspiration (FNA) is a popular method for evaluating pancreatic lesions. There is considerable literature on FNA evaluation of primary pancreatic carcinomas, but few studies address the FNA diagnosis of primary pancreatic lymphoma. We reviewed 14 cases of atypical lymphoid processes diagnosed by FNA during a 5-year period, constituting 1.3% of a total of 1,050 pancreatic FNA cases. The diagnoses were as follows: 6 large B-cell lymphomas, 4 follicular lymphomas, 3 suggestive of lymphoma, and 1 unclassified B-cell lymphoma. Lymphoid neoplasms manifested in older people (mean age, 64.7 years) as a solitary mass in the pancreatic head, mimicking primary carcinoma. Clonality was confirmed by flow cytometry in 11 cases and immunohistochemical analysis on cell block material in 2. Obtaining diagnostic material often required several passes (average, 3.9 passes; range, 1-8 passes). We conclude that primary pancreatic lymphomas rarely are diagnosed by FNA, tend to be high grade, and clinically and radiographically might mimic primary carcinoma.

Infantile fibromatosis of the external genitalia: diagnosis and management strategy.

Infantile fibromatosis is a process that is difficult to distinguish from fibrosarcoma. It is found in neonates and infants but only rarely has it been reported to involve the external genitalia or scrotum. A 10-month-old boy is described with histologically proved infantile fibromatosis of the scrotum. Characteristics distinguishing infantile fibromatosis from fibrosarcoma and the appropriate management of this disease are presented.

Coincident Merkel cell carcinoma and B-cell lymphoma: a report of two cases evaluated by cytology.

Dear Dr. Bedrossian: Merkel cell carcinoma (MCC) is a rare neuroendocrine malignancy of the skin, characterized by an aggressive course with frequent local recurrence, metastatic spread, and a high mortality. Risk factors include ultraviolet light exposure and immunosuppressed states. B-cell lymphomas, like MCC, tend to affect older patients and are associated with second primary malignancies. Evaluation of SEER data has shown an increase in site-specific risk for non-Hodgkin lymphoma in patients with MCC. These studies have also shown a significant risk of MCC as a second primary in patients with both chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and other non-Hodgkin lymphomas. MCC and small B-cell lymphomas share many cytologic characteristics. The differential of “small round blue cell tumors” includes MCC and small B cell lymphomas as well as small cell carcinoma, melanoma, and numerous childhood malignancies. In light of their epidemiologic coincidence, these morphologic similarities may present a dilemma, particularly during on-site cytology assessments. We recently encountered two patients who were diagnosed by needle biopsy, one with concurrent CLL and MCC and one with follicular lymphoma and MCC. A 69-year-old male with history of CLL/SLL and MCC of the right forearm presented for evaluation of a new axillary mass. The patient had previously undergone a wide, local excision for MCC and sentinel lymph nodes from the axilla showed CLL, but were negative for MCC. Four months after surgery, a new mass in the right axilla was noted, and he presented for ultrasound-guided biopsy. On immediate assessment, touch preparations of core biopsies stained with Diff-Quik were highly cellular, consisting of small to medium sized cells with scant cytoplasm and evenly dispersed chromatin (Fig. 1A). Crush artifact and focal areas of molding were noted. There were rare mitotic figures and karryorhectic debris. Lymphoglandular bodies were not evident. Additional core biopsies were obtained, and the specimen was divided and sent for both flow cytometric immunophenotyping and paraffin embedding. The core biopsies showed an infiltrating population of small cells, with nuclear molding and minimal cytoplasm (Fig. 1B). Immunohistochemical studies revealed these cells to be reactive for pancytokeratin and CK20 (in a perinuclear dot-like pattern, Fig. 1C) and negative for CD45 and CD20, consistent with metastatic MCC. Clusters of small lymphocytes, which stained positively for CD20 (Fig. 1D) and CD45, were interspersed. Flow cytometry revealed a phenotypically abnormal population of small lymphocytes which expressed B-cell associated antigens, CD19 and CD20, CD5, and low intensity monoclonal surface immunoglobulin of lambda isotype. Cells were negative for CD10. This was consistent with simultaneous involvement by the patient’s CLL/SLL. The second patient was a 63-year-old male with history of immunosuppressive therapy for rheumatoid arthritis and MCC who presented for evaluation of retroperitoneal lymphadenopathy. Touch preparations of core biopsies stained with Diff-Quik at immediate assessment showed abundant small cells with some clumping and crush artifact (Fig. 2A). The possibilities of metastatic MCC or a new lymphoma were considered. Needle aspirate material was sent for flow cytometry, and the remaining core material was retained in formalin. Core biopsy showed sheets of small lymphoid cells, with a few scattered larger cells (Fig. 2B), which expressed CD20 (Fig. 2C), CD45, CD10, CD23, Bcl-6, and Bcl-2. CD5, CD43, Mum1, Cyclin D1, pancytokeratin, synaptophysin, chromogranin, and CK20 were not expressed in these cells, though CD21 *Correspondence to: Trisha M. Shattuck, M.D., PH.D., Duke University Medical Center, Box 3712, Durham, NC 27710, USA. E-mail: trisha.shattuck@duke.edu Received 5 October 2012; Accepted 4 April 2013 DOI 10.1002/dc.23011 Published online 11 June 2013 in Wiley Online Library (wileyonlinelibrary.com).

Primary pancreatic lymphoma evaluated by fine-needle aspiration

Fine-needle aspiration (FNA) is a popular method for evaluating pancreatic lesions. There is considerable literature on FNA evaluation of primary pancreatic carcinomas, but few studies address the FNA diagnosis of primary pancreatic lymphoma. We reviewed 14 cases of atypical lymphoid processes diagnosed by FNA during a 5-year period, constituting 1.3% of a total of 1,050 pancreatic FNA cases. The diagnoses were as follows: 6 large B-cell lymphomas, 4 follicular lymphomas, 3 suggestive of lymphoma, and 1 unclassified B-cell lymphoma. Lymphoid neoplasms manifested in older people (mean age, 64.7 years) as a solitary mass in the pancreatic head, mimicking primary carcinoma. Clonality was confirmed by flow cytometry in 11 cases and immunohistochemical analysis on cell block material in 2. Obtaining diagnostic material often required several passes (average, 3.9 passes; range, 1–8 passes). We conclude that primary pancreatic lymphomas rarely are diagnosed by FNA, tend to be high grade, and clinically and radiographically might mimic primary carcinoma.

A developmental approach to preschool vision screening.

A developmental approach to preschool vision screening is described. The choice of acuity testing material in this test is determined by the childs capabilities, assessed prior to acuity testing. When compared with the Society for Prevention of Blindness test, this approach yields approximately half the number of untestables. Further, the acuity data from the two screening tests are quite similar, and both agree well with data from an additional screening by a pediatric ophthalmologist. Screening of preschool children usually requires a number of compromises in methods felt to be ideal for adults. Sacrifices in cost (i.e., additional personnel to assist the tester), additional effort (i.e., prior training of the children), or precision of acuity measures (i.e., cruder picture type targets for all children and use of isolated targets) are typically made to assure testability. These problems have been minimized by the Experimental method. Because of its low untestability rate and its apparently valid acuity data, this developmental vision screening test can be recommended as a cost effective approach to preschool vision screening. Previous research has shown that ratings of a childs behavior during this developmentally oriented vision screening test predict results of diagnostic cognitive tests as accurately as extensive tests designed exclusively for developmental screening. This test is then extremely cost effective when used for comprehensive preschool screening.

The utility of thyroglobulin washout studies in predicting cervical lymph node metastases: One academic medical center's experience

Fine‐needle aspiration cytology (FNAC) is useful for evaluating cervical lymph nodes for metastases from thyroid carcinomas. Reports have illustrated that with application of standardized technique and appropriate cutoffs, thyroglobulin (TG) washout studies increase the sensitivity and specificity of FNAC in identifying lymph node metastases. This project describes our experience at an academic medical center utilizing needle wash thyroglobulin analyses as an ancillary to FNAC.