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Small Lymphocytic Pulmonary Lymphoma
Small Lymphocytic Pulmonary Lymphoma* Diagnosis by Transthoracic Fine Needle Aspiration RDbert I . Sprague, M.D. ;t and Georgean G. deBlois M.D.*
A 77-year-old woman was found to have multiple densities on chest roentgenogram. Exfoliative cytology, bronchoscopy with brushings and washings, and traosbronchial biopsy revealed a monomorphic population of small lymphocytes suggestive of lymphoma. Transthoracic fine-needle aspiration was performed to provide additional material for immunologic marker study. Immunocytochemistry revealed a monoclonal population of B-ceUs, which confirmed a diagnosis of small lymphocytic lymphoma. Chemotherapy resulted in significant clinical and roentgenographic improvement. (Cheat 1989; 96:929-30) fine-needle aspiration (TFNA) cytology is T aransthoracic reliable and safe alternative to thoracotomy in the
diagnosis and management of selected pulmonary lesions. 1-3 Most studies have concentrated on its efficacy in epithelial malignancies.'? As this report indicates, however, TFNA may also significantly contribute to the diagnosis of pulmonary Iymphoproliferative lesions. Aspirated material is an excellent substrate for both surface and cytoplasmic immunologic marker studies.' Thus, immunocytochemistry in conjunction with cytology can help differentiate monoclonal neoplastic lymphoid populations from benign polyclonal lymphoid infiltrates.<-8 CASE REPORT A 77-year-old white woman nonsmoker was admitted to the Medical College of Virginia Hospital for evaluation of bilateral lower lung zone densities. The patient reported a 22.6 kg (50 pound) weight loss over the past two years and slight dyspnea on exertion. She denied anorexia, cough, fever, chills, hemoptysis, chest pain or exposure to tuberculosis. Her past medical history was notable for ep isodes of complete heart block which required a pacemaker. Physical examination demonstrated increased intensity of breath sounds at the left lung base associated with bilateral expiratory wheezes. There was no evidence of peripheral lymphadenopathy. Admission laboratory results were noncontributory. A complete blood cell count and differential blood count results were within nonnallimits. Chest x-ray film revealed an 8 X 8 em mass in the left lower lobe with several small densities in the right middle and right lower lobes (Fig 1). There was no hilar adenopathy. Flexible fiberoptic bronchoscopy was performed, Signs of external compression were noted in the trachea and both mainstem bronchi. The carina appeared slightly fixed, broadened, and edematous. There was narrowing of left upper and lower lobe takeoffs. The bronchial mucosa was friable and bled easily. Bronchial washing and brushing specimens, transbronchial biopsy and concurrent sputum specimens contained a monomorphic population of small round lymphocytes suggestive of a pulmonary Iymphoproliferative disorder (Fig 2). A fluoroscopically-guided percutaneous TFNA was perfonned ·From the Department of Pathology, Medical College of Virginia, Virginia Commonwealth University, Richmond. tResident in Pathology. *Assistant Professor of Pathology. Reprint requests: Dr: deBlois, johnston-WllUs Hoapltal, Richmond, VA 23235
FIGURE 1. Initial PA chest roentgenogram showing prominent bilateral lower lobe densities. under local anesthesia. Material was aspirated from a left basilar mass using a 2O-gauge Turner needle through an IS-gauge Turnerneedle introducer. In addition to air dried and alcohol-fixed smears, a portion of the specimen was placed in 5 ml of cold (4°C) RPMI1640 with 10 percent fetal calf serum culture media. AiNlried smears were stained with a modified Wright's stain ; and alcohol fixed smears were stained by the Papanicolaou method. Cytospin preparations were made from the material in RPMI and immunologic marker studies were performed with monoclonal antibodies to IgM , IgG, IgA, kappa and lambda using the avidin-biotin technique.' Cytologically, the aspirate was cons istent with a small lymphocytic (well differentiated) lymphoma. Immunocytochemical studies corroborated the diagnosis oflymphoma by demonstrating a monoclonal population of B-cells which expressed IgM and lambda cell-surface markers (Fig 3). Staging evaluation, including a bone marrow aspiration and biopsy, failed to show evidence of extrapulmonary disease.
FIGURE 2. Bronchial brushing revealed a monomorphous population of small , round lymphocytes (Papanicolaou, original magnification xSOO). CHEST I 96 I 4 I OClOBER, 1989
929
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FIGURE 3. The neoplastic lymphocytes react strongly with the antibody to the lambda light chain monoclonal cell-surface marker (A, upper). In contrast (B, lower). there is no reactivity with the antibody to kappa light chain (Avidin-biotin, original magnification x 7(0). Fol1owing discharge . the patient received eight months of orally given chlorambucil (2 mg/day), Her symptoms resolved , and there was dramatic resolution of the pulmonary densities noted on her initial x-ray examination. DISCUSSION
Pulmonary lymphoproliferative disorders represent a well-recognized area of diagnostic difficulty.5.7 Most patients clinically suspected of having a pulmonary lymphoproliferative disorder are subjected to open lung biopsy in an effort to obtain adequate diagnostic material . However, even with adequate material, the pathologist may not be able to make an unequivocal histologic diagnosis of lymphoma," This is especially true for the small lymphocytic (well differentiated) lymphomas which can morphologically resemble reactive lymphoid proliferations," The diagnosis of lymphoma has evolved beyond strictly morphologic criteria with recognition that a neoplastic lymphoid process represents a monoclonal proliferation. Thus, immunologic marker studies have become an impor tant adjunct in the diagnosis of lymphoma..... Although cellsurface marker studies can often provide unequivocal evi930
dence of a monoclonal lymphoid process, this technique can only be applied to limited material, (ie, fresh or frozen tissue). Paraffin-embedded, formalin-fixed tissue , while suitable for the occasional plasmacytoid lymphoma with cytoplasmic light chains, is not optimal for cell surface marker studies.' Cytologic preparations made from material 0btained by TFNA prove to be an excellent substrate for cellsurface marker studies. ' The TFNA, in conjunction with immunocytochemistry, can reliably aid in the following: (1) the differentiation of benign lymphoproliferative lesions from small lymphocytic lymphoma; (2) the distinction oflarge cell lymphomas from the more common epithelial malignancies (by using a battery of lymphoid and epithelial cell markers) ; and (3) the identification of B-cell or T-cell origin of lymphoproliferative disorders. The low morbidity of fine needle aspiration also makes it useful in confirming recurrence.' To maximize the diagnostic yield of TFNA in suspected cases of pulmonary lymphoproliferative disorders, certain technical considerations must be met. High quality smears are essential; a cytotechnologist or cytopathologist should be on site to prepare smears. Aspirated material should be placed in a balanced electrolyte solution for cytospin preparations as well as in standard tissue fixative for cell blocks. For cell-surface marker studies, a portion of the specimen must be placed in cold RPM!. To overcome the potential problem of inadequate sampling, several aspirates can be performed. The use of a small gauge needle minimizes the risk of pneumothorax.' In summary, TFNA can prove useful in the diagnosis of pulmonary lymphoproliferative lesions and may eliminate the need for open-lung biopsy. However, even under optimal circumstances, the diagnosis of low grade lymphomas may be difficult and should be made with caution. The cytopathologic findings must be correlated with clinical features, roentgenographic findings, and laboratory data such as complete blood count with differential and serum protein electrophoresis. REFERENCES
1 Crosby JH . Hager B, Hoeg K. Transthoracic Bne-needle aspiration: experience in a cancer center. Cancer 1985: 56:2504-07 2 Malberger E, Lemberg S. Transthoracic fine needle aspiration cytology; a study of 301 aspirations from 221 cases. Acta Cytol 1982; 26:172-78 3 Young Gp, Young I, Cowan OF, Blei RL. The reliability of flneneedle aspiration biopsy in the diagnosis of deep lesions of the lung and mediastinum: experience using a modified technique. Diag Cytopatholl987; 3:1-7 4 Levitt 5, Cheng L, OePuis MH . Layfield LJ. Fine needle aspiration diagnosis of malignant lymphoma with conflnnation by immunoperoxidase staining. Acta Cytoll985; 29:895-902 5 Colby Tv, Carrington CB. Pulmonary lymphomas: current concepts. Hum Patholl983: 14:884-87 6 Gephard GO, Tubbs RR, Liu AC, Petros RE, Ahmad M, Golish JA, et al. Pulmonary lymphoid neoplasms : role of immunohistology in the study of cel1ular immunotypes and in the 'differential diagnosis. Chest 1986: 89:545-50 7 Kennedy JL, Nathwani BN, Burlce JS, Hill LR, Rappaport H. Pulmonary lymphomas and other pulmonary lymphoid lesions. Cancer 1985; 56:539-52 8 Peterson H, Snider HL, Yam LT. Bowlds CF. Arnn EH, Li CY. Primary pulmonary lymphoma: a clinical and immunohistochemical study of six cases. Cancer 1985: 56:805-13 Small Lymphocytk: Pulmonary Lymphoma (Sprague, deBloi4)
A 77-year-old woman was found to have multiple densities on chest roentgenogram. Exfoliative cytology, bronchoscopy with brushings and washings, and traosbronchial biopsy revealed a monomorphic population of small lymphocytes suggestive of lymphoma. Transthoracic fine-needle aspiration was performed to provide additional material for immunologic marker study. Immunocytochemistry revealed a monoclonal population of B-ceUs, which confirmed a diagnosis of small lymphocytic lymphoma. Chemotherapy resulted in significant clinical and roentgenographic improvement. (Cheat 1989; 96:929-30) fine-needle aspiration (TFNA) cytology is T aransthoracic reliable and safe alternative to thoracotomy in the
diagnosis and management of selected pulmonary lesions. 1-3 Most studies have concentrated on its efficacy in epithelial malignancies.'? As this report indicates, however, TFNA may also significantly contribute to the diagnosis of pulmonary Iymphoproliferative lesions. Aspirated material is an excellent substrate for both surface and cytoplasmic immunologic marker studies.' Thus, immunocytochemistry in conjunction with cytology can help differentiate monoclonal neoplastic lymphoid populations from benign polyclonal lymphoid infiltrates.<-8 CASE REPORT A 77-year-old white woman nonsmoker was admitted to the Medical College of Virginia Hospital for evaluation of bilateral lower lung zone densities. The patient reported a 22.6 kg (50 pound) weight loss over the past two years and slight dyspnea on exertion. She denied anorexia, cough, fever, chills, hemoptysis, chest pain or exposure to tuberculosis. Her past medical history was notable for ep isodes of complete heart block which required a pacemaker. Physical examination demonstrated increased intensity of breath sounds at the left lung base associated with bilateral expiratory wheezes. There was no evidence of peripheral lymphadenopathy. Admission laboratory results were noncontributory. A complete blood cell count and differential blood count results were within nonnallimits. Chest x-ray film revealed an 8 X 8 em mass in the left lower lobe with several small densities in the right middle and right lower lobes (Fig 1). There was no hilar adenopathy. Flexible fiberoptic bronchoscopy was performed, Signs of external compression were noted in the trachea and both mainstem bronchi. The carina appeared slightly fixed, broadened, and edematous. There was narrowing of left upper and lower lobe takeoffs. The bronchial mucosa was friable and bled easily. Bronchial washing and brushing specimens, transbronchial biopsy and concurrent sputum specimens contained a monomorphic population of small round lymphocytes suggestive of a pulmonary Iymphoproliferative disorder (Fig 2). A fluoroscopically-guided percutaneous TFNA was perfonned ·From the Department of Pathology, Medical College of Virginia, Virginia Commonwealth University, Richmond. tResident in Pathology. *Assistant Professor of Pathology. Reprint requests: Dr: deBlois, johnston-WllUs Hoapltal, Richmond, VA 23235
FIGURE 1. Initial PA chest roentgenogram showing prominent bilateral lower lobe densities. under local anesthesia. Material was aspirated from a left basilar mass using a 2O-gauge Turner needle through an IS-gauge Turnerneedle introducer. In addition to air dried and alcohol-fixed smears, a portion of the specimen was placed in 5 ml of cold (4°C) RPMI1640 with 10 percent fetal calf serum culture media. AiNlried smears were stained with a modified Wright's stain ; and alcohol fixed smears were stained by the Papanicolaou method. Cytospin preparations were made from the material in RPMI and immunologic marker studies were performed with monoclonal antibodies to IgM , IgG, IgA, kappa and lambda using the avidin-biotin technique.' Cytologically, the aspirate was cons istent with a small lymphocytic (well differentiated) lymphoma. Immunocytochemical studies corroborated the diagnosis oflymphoma by demonstrating a monoclonal population of B-cells which expressed IgM and lambda cell-surface markers (Fig 3). Staging evaluation, including a bone marrow aspiration and biopsy, failed to show evidence of extrapulmonary disease.
FIGURE 2. Bronchial brushing revealed a monomorphous population of small , round lymphocytes (Papanicolaou, original magnification xSOO). CHEST I 96 I 4 I OClOBER, 1989
929
·'"
_: t ~~.. . . . '
t,· .' . -.
' ",
•
( , "\
."
(
,""
- ~f
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FIGURE 3. The neoplastic lymphocytes react strongly with the antibody to the lambda light chain monoclonal cell-surface marker (A, upper). In contrast (B, lower). there is no reactivity with the antibody to kappa light chain (Avidin-biotin, original magnification x 7(0). Fol1owing discharge . the patient received eight months of orally given chlorambucil (2 mg/day), Her symptoms resolved , and there was dramatic resolution of the pulmonary densities noted on her initial x-ray examination. DISCUSSION
Pulmonary lymphoproliferative disorders represent a well-recognized area of diagnostic difficulty.5.7 Most patients clinically suspected of having a pulmonary lymphoproliferative disorder are subjected to open lung biopsy in an effort to obtain adequate diagnostic material . However, even with adequate material, the pathologist may not be able to make an unequivocal histologic diagnosis of lymphoma," This is especially true for the small lymphocytic (well differentiated) lymphomas which can morphologically resemble reactive lymphoid proliferations," The diagnosis of lymphoma has evolved beyond strictly morphologic criteria with recognition that a neoplastic lymphoid process represents a monoclonal proliferation. Thus, immunologic marker studies have become an impor tant adjunct in the diagnosis of lymphoma..... Although cellsurface marker studies can often provide unequivocal evi930
dence of a monoclonal lymphoid process, this technique can only be applied to limited material, (ie, fresh or frozen tissue). Paraffin-embedded, formalin-fixed tissue , while suitable for the occasional plasmacytoid lymphoma with cytoplasmic light chains, is not optimal for cell surface marker studies.' Cytologic preparations made from material 0btained by TFNA prove to be an excellent substrate for cellsurface marker studies. ' The TFNA, in conjunction with immunocytochemistry, can reliably aid in the following: (1) the differentiation of benign lymphoproliferative lesions from small lymphocytic lymphoma; (2) the distinction oflarge cell lymphomas from the more common epithelial malignancies (by using a battery of lymphoid and epithelial cell markers) ; and (3) the identification of B-cell or T-cell origin of lymphoproliferative disorders. The low morbidity of fine needle aspiration also makes it useful in confirming recurrence.' To maximize the diagnostic yield of TFNA in suspected cases of pulmonary lymphoproliferative disorders, certain technical considerations must be met. High quality smears are essential; a cytotechnologist or cytopathologist should be on site to prepare smears. Aspirated material should be placed in a balanced electrolyte solution for cytospin preparations as well as in standard tissue fixative for cell blocks. For cell-surface marker studies, a portion of the specimen must be placed in cold RPM!. To overcome the potential problem of inadequate sampling, several aspirates can be performed. The use of a small gauge needle minimizes the risk of pneumothorax.' In summary, TFNA can prove useful in the diagnosis of pulmonary lymphoproliferative lesions and may eliminate the need for open-lung biopsy. However, even under optimal circumstances, the diagnosis of low grade lymphomas may be difficult and should be made with caution. The cytopathologic findings must be correlated with clinical features, roentgenographic findings, and laboratory data such as complete blood count with differential and serum protein electrophoresis. REFERENCES
1 Crosby JH . Hager B, Hoeg K. Transthoracic Bne-needle aspiration: experience in a cancer center. Cancer 1985: 56:2504-07 2 Malberger E, Lemberg S. Transthoracic fine needle aspiration cytology; a study of 301 aspirations from 221 cases. Acta Cytol 1982; 26:172-78 3 Young Gp, Young I, Cowan OF, Blei RL. The reliability of flneneedle aspiration biopsy in the diagnosis of deep lesions of the lung and mediastinum: experience using a modified technique. Diag Cytopatholl987; 3:1-7 4 Levitt 5, Cheng L, OePuis MH . Layfield LJ. Fine needle aspiration diagnosis of malignant lymphoma with conflnnation by immunoperoxidase staining. Acta Cytoll985; 29:895-902 5 Colby Tv, Carrington CB. Pulmonary lymphomas: current concepts. Hum Patholl983: 14:884-87 6 Gephard GO, Tubbs RR, Liu AC, Petros RE, Ahmad M, Golish JA, et al. Pulmonary lymphoid neoplasms : role of immunohistology in the study of cel1ular immunotypes and in the 'differential diagnosis. Chest 1986: 89:545-50 7 Kennedy JL, Nathwani BN, Burlce JS, Hill LR, Rappaport H. Pulmonary lymphomas and other pulmonary lymphoid lesions. Cancer 1985; 56:539-52 8 Peterson H, Snider HL, Yam LT. Bowlds CF. Arnn EH, Li CY. Primary pulmonary lymphoma: a clinical and immunohistochemical study of six cases. Cancer 1985: 56:805-13 Small Lymphocytk: Pulmonary Lymphoma (Sprague, deBloi4)