- Email: [email protected]
Peripheral T-Cell Lymphoma Simulating Hodgkin's Disease With Initial Bone Marrow Involvement
Case Report Peripheral T-Cell Lymphoma Simulating Hodgkin's Disease With Initial Bone Marrow Involvement GERARDO COLON-OTERO, M . D . , Resident in Hematology*; STEPHEN P. McCLURE, M . D . , Resident in Pathologyl·; ROBERT L. PHYLIKY, M . D . , WILLIAM L. WHITE, M . D . , Division of Hematology and Internal Medicine; PETER M . BANKS, M . D . , Section of Surgical Pathology
In a patient who had fever and cytopenias but no peripheral lymphadenopathy, bone marrow biopsy revealed findings consistent with Hodgkin's disease. Subsequently lymph node biopsy specimens showed lymphoma with features more consistent with peripheral T-cell lymphoma. The clinical features of this patient were those that have been ascribed to an atypical clinical form of Hodgkin's disease. This case illustrates the inadequacy of bone marrow examination as the sole criterion for establishing an initial diagnosis of Hodgkin's disease, particularly in relationship to the newly recognized pleomorphic variants of T-cell malignant lymphoma.
An atypical clinical form of Hodgkin's disease featuring predominant subdiaphragmatic involvement, extensive bone marrow infiltration, fevers, pancytopenia, absence of peripheral lymphadenopathy, and frequently a rapidly progressive course has been described. 1,2 This syndrome has been associated with various histologic subtypes of Hodgkin's disease, most commonly lymphocytic de pletion and mixed cellularity. 2,3 Performance of bone marrow aspiration and biopsy has been recommended in patients with clinical features suggestive of this syn drome, inasmuch as diagnostic information obtained with use of this procedure may obviate the need for laparotomy. 2 In this report, we describe a patient with clinical fea tures and bone marrow findings consistent with an atyp ical clinical form of Hodgkin's disease but in whom
subsequent lymph node biopsy specimens were consis tent with a diagnosis of a peripheral T-cell lymphoma. The potential implications of these findings are discussed herein.
MATERIAL AND METHODS Bone marrow aspirate smears and biopsy sections were processed by conventional methods and stained with Wright's stain and hematoxylin and eosin, respectively. Hematoxylin and eosin-stained lymph node sections were examined. Frozen sections and air-dried imprint preparations of lymph node tissue from our patient were analyzed for the presence of antigenic determinants by the use of commercially prepared primary monoclonal antibodies Leu-1, Leu-2a, and Leu-3a (Beckton Dickin son Monoclonal Antibody Center, Sunnyvale, California) and B-1 (Coulter Electronics, Inc., Hialeah, Florida). In a two-step immunostaining method, goat-antimouse peroxidase-conjugated serum (TACO, Inc., Burlingame, California) was used. Affinity column purified F(ab')2 antisera against human κ and λ immunoglobulin light chains (goat peroxidase-conjugated, TAGO, Inc.) were also used on the frozen sections.
*Mayo Graduate School of Medicine, Rochester, Minnesota. Present address: Charlottesville, Virginia. tMayo Graduate School of Medicine, Rochester, Minnesota. Present address: Akron, Ohio. Address reprint requests to Dr. R. L. Phyliky, Division of Hematology, Mayo Clinic, Rochester, MN 55905. Mayo Clin Proc 61:68-71, 1986
68
Mayo Clin Proc, January 1986, Vol 61
T-CELL LYMPHOMA SIMULATING HODGKIN'S DISEASE
69
REPORT OF CASE A 44-year-old woman had a 2-month history of fevers and sweats. Physical examination revealed hepatomegaly, shotty right inguinal nodes, and a systolic heart murmur. Results of blood studies disclosed a hemoglobin concentration of 6.2 g/dl, and a complete blood cell count revealed a leukocyte count of 2,100/mm 3 and a platelet count of 112,000/mm 3 . The differential leukocyte count showed 69% polymorphonuclear cells, 8% bands, 1 7% lymphocytes, 5% monocytes, and 1 % myelocytes. The reticulocyte count was 0.8%, a direct antiglobulin (Coombs') test was negative, a peripheral blood smear lacked diagnostic features, and levels of serum vitamin B12 and folate were within normal limits. Serum protein electrophoresis revealed a low albumin level (1.58 g/dl) but a normal 7-globulin level. Immunoelectrophoresis studies of serum and urine showed no monoclonal proteins. The serum calcium level was 7.4 mg/dl (normal range, 8.9 to 10.1 mg/dl), and results of liver function tests were as follows: serum alkaline phosphatase, 397 U/liter (normal range, 76 to 196 U/liter); serum aspartate aminotransferase, 59 U/liter (normal range, 12 to 31 U/liter); and serum total and direct bilirubin, normal. Multiple blood cultures for fungi and bacteria were negative. Roentgenograms of the chest revealed normal findings. Computed tomographic scans of the abdomen at this time disclosed retroperitoneal lymphadenopathy and also hepatosplenomegaly.
Fig. 1. Bone marrow biopsy specimen, showing neoplastic giant cells with multiple nuclear lobes and macronucleoli, features initially interpreted as diagnostic of Hodgkin's disease. (Hematoxylin and eosin; x640.)
A bone marrow aspirate was nondiagnostic. A bone marrow biopsy specimen showed moderate hypercellularity, focal myelofibrosis, and diffuse infiltration by lymphocytes and atypical large cells, including some multinucleated neoplastic giant cells (Reed-Sternberg cells) (Fig. 1). These findings were thought to be diagnostic of Hodgkin's disease. Biopsy of a slightly enlarged right inguinal lymph node, however, revealed a lymphomatous process that had both morphologic and immunologic features of a pleomorphic (T-cell) non-Hodgkin's neoplasm. The nodal architecture was only partially effaced, and the paracortex was selectively replaced by an abnormal, heterogeneous proliferation of cells (Fig. 2 A). Highmagnification microscopy revealed a continuum of abnormal lymphoid cells, between tumor giant cells with multilobated nuclei and multiple nucleoli and atypical small lymphocytes with irregular, complex nuclear membranes (Fig. 2 ß). The atypia of the small lymphocytic mil ieu that surrounded the tumor giant eel Is was considered not consistent with Hodgkin's disease. Immunostaining suggested the process to be of T-cell na-
ture. In both frozen sections and air-dried imprint preparations, 90% of the cells in the zones of neoplastic involvement, including the large cells, stained for Leu-1 (pan-T-cell) antigen. In the frozen-section preparations, the neoplastic regions stained predominantly (80 to 90%) for Leu-3a (helper/inducer) antigen, whereas only about 10% stained for Leu-2a (suppressor/cytotoxic) antigen and 10% stained for B-1 (pan-B-cell) antigen, κ and λ light chains were demonstrated in equal cellular dis tributions, almost exclusively in the benign portions of the lymph node. The patient's diagnosis was revised to diffuse mixed-type lymphoma, pleomorphic variant, of apparent T-cell immunotype. The patient received one course of multiple-agent chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone), but liver failure ensued and she died within 6 weeks after diagnosis. Autopsy revealed advanced lymphomatous involvement of the liver, spleen, abdominal lymph nodes, and bone marrow. The pattern of splenic involvement by lymphoma—namely, dispersed sinusoidal infiltration—was more consistent
70
T-CELL LYMPHOMA SIMULATING HODGKIN'S DISEASE
Mayo Clin Proc, January 1986, Vol 61
Fig. 2. A, Inguinal lymph node biopsy specimen, showing partial preservation of normal functional cellular components and paracortical zones of heterogeneous neoplastic cellularity (arrows). (Hematoxylin and eosin; x40.) B, Higher-magnification appearance of neoplastic paracortical process, with giant cells surrounded by atypical mononuclear forms. Note that even medium and small-sized lymphocytes contain complex, irregularly shaped nuclei, in contrast to benign, normal-appearing lymphoid background characteristic of Hodgkin's disease. (Hematoxylin and eosin; x640.)
with non-Hodgkin's (T-cell) lymphoma than with Hodgkin's disease, which is characterized by expansive, cohesive tumorous nodules. DISCUSSION Peripheral T-cell lymphoma 4 is a recently recognized, immunologically defined grouping of malignant lymphomas of T-cell origin that has been designated variously as T-immunoblastic sarcoma, 5 node-based T-cell lymphoma, 5 T-zone lymphoma, c> pleomorphic lymphoma, 7 lymphoepithelioid cell lymphoma, 5 and multilobated T-cell lymphoma. 8 A subset of patients with this condition have a distinct clinicopathologic entity called adult T-cell leukemia-lymphoma that has been associated with the human T-cell leukemia virus I. 9 "' 1 Clusters of adult T-cell leukemia-lymphoma have been described in Japan, the Caribbean, and southeastern United States. Clinically, patients with peripheral T-cell lymphomas often have advanced disease and an aggressive course. A
median duration of survival of less than 12 months (mean, 10.9 months) has been reported. 1 2 ' 3 Histologically, peripheral T-cell lymphomas are characterized by a diffuse pleomorphic lymphoid infiltrate composed of small lymphoid cells with irregular hypersegmented nuclei and large lymphoid cells that have abundant clear cytoplasm and round nuclei with prominent nucleoli and striking multilobulation. 1 4 Immunologie studies reveal the T-cell nature of these neoplastic cells. Increased vascularity and compartmentalization are other features that have been noted. The appearance of the large neoplastic cells can be confused with that of Reed-Sternberg cells. Although the neoplastic T-lymphocytes usually have nuclei with greater lobulations and smaller nucleoli than those of Reed-Sternberg cells, these distinguishing features can be exceedingly subtle. The pleomorphic nature of the neoplastic lymphoid infiltrate in peripheral T-cell lymphomas, a feature usually lacking in Hodgkin's disease,
Mayo Clin Proc, January 1986, Vol 61
may be difficult to appreciate in small extranodal biopsy samples.15 As shown by the case presented herein, the clinical manifestations in patients with peripheral T-cell lymphomas can resemble an atypical clinical form of Hodgkin's disease. Thus, Hodgkin's disease can be incorrectly diagnosed in patients with peripheral T-cell lymphomas on the basis of bone marrow biopsy findings alone. The correct classification of the neoplastic lymphoid process in such patients can have important therapeutic, prognostic, and epidemiologic implications. Therefore, we recommend that physicians resist the temptation to accept a diagnosis of Hodgkin's disease based only on bone marrow biopsy findings. A careful search for lymphadenopathy should be made in the hope of obtaining nodal tissue for histologic and immunologic examinations. If the medical condition of the patient precludes a surgical procedure, immunologic studies of the bone marrow tissue to determine whether the neoplastic cells are of T-cell origin can provide additional helpful information. ACKNOWLEDGMENT We thank Wendy K. Hollingsworth for secretarial assistance with the original manuscript. REFERENCES 1.
2.
Longcope W T : Hodgkin's disease. In The Oxford Medicine. Part 1, Vol 4. Edited by HA Christian. New York, Oxford University Press, 1949, pp 1-44 Neiman RS, Rosen PJ, Lukes R): Lymphocyte-depletion Hodgkin's disease: a c l i n i c o p a t h o l o g i c a l entity. N EngI ) Med 288:751-755, 1973
T-CELL LYMPHOMA SIMULATING HODGKIN'S DISEASE
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14. 15.
71
Sobrinho-Simoes M , Paiva ME, Goncalves V, Saldanha C, Vaz Saleiro J, Serrao D: Hodgkin's disease with predominant i n fradiaphragmatic involvement and massive invasion of the bone marrow: a necropsic study of nine cases. Cancer 52:1927-1932, 1983 Waldron JA, Leech JH, Glick A D , FlexnerJM, Collins RD: Malignant lymphoma of peripheral T-lymphocyte origin: i m m u nologic, pathologic, and clinical features in six patients. Cancer 40:1604-1617, 1977 Collins RD, Waldron JA, Glick A D : Results of multiparameter studies of T-cell l y m p h o i d neoplasms. A m J Clin Pathol 72:699-707, 1979 Lennert K: Malignant Lymphomas Other Than Hodgkin's Disease: Histology, Cytology, Ultrastructure, Immunology. New York, Springer-Verlag, 1978 WatanabeS, NakajimaT, Shimosato Y, ShimoyamaM, MinatoK: T-cell malignancies: subclassification and interrelationship. JpnJ Clin Oncol 9 Suppl:423-442, 1979 Pinkus GS, Said JW, Hargreaves H: Malignant lymphoma, T-cell type: a distinct morphologic variant with large multilobated nuclei, with a report of four cases. Am J Clin Pathol 72:540-550, 1979 Gallo RC, de The GB, Ito Y: Kyoto workshop on some specific recent advances in h u m a n t u m o r v i r o l o g y . Cancer Res 41:4738-4739, 1981 Catovsky D, Rose M , Goolden A W G , White JM, Bourikas G, Brownell A I , Blattner W A , Greaves MF, Galton DAG, McCIuskey DR, Lampert I, Ireland R, Bridges JM, Gallo RC: Adult T-cell lymphoma-leukaemia in Blacks from the West Indies. Lancet 1:639-643, 1982 Blayney D W , Jaffe ES, Blattner W A , CossmanJ, Robert-Guroff M , Longo DL, Bunn PA Jr, Gallo RC: The human T-cell leukemia/ lymphoma virus associated with American adult T-cell leukemia/ lymphoma. Blood 62:401-405, 1983 Brisbane JU, Berman LD, Neiman RS: Peripheral T-cell lymphoma: a clinicopathologic study of nine cases. A m J Clin Pathol 79:285-293, 1983 GreerJP, YorkJC, CousarJB, Mitchell RT, FlexnerJM, Collins RD, Stein RS: Peripheral T-cell lymphoma: a clinicopathologic study of 42 cases. J Clin Oncol 2:788-798, 1984 N e i m a n RS: I m m u n o b l a s t i c sarcoma. A m J Surg Pathol 6:755-760, 1982 Wright D H , Isaacson PG: Biopsy Pathology of the Lymphoreticular System. Baltimore, Williams & Wilkins Company, 1983, pp 215-219
In a patient who had fever and cytopenias but no peripheral lymphadenopathy, bone marrow biopsy revealed findings consistent with Hodgkin's disease. Subsequently lymph node biopsy specimens showed lymphoma with features more consistent with peripheral T-cell lymphoma. The clinical features of this patient were those that have been ascribed to an atypical clinical form of Hodgkin's disease. This case illustrates the inadequacy of bone marrow examination as the sole criterion for establishing an initial diagnosis of Hodgkin's disease, particularly in relationship to the newly recognized pleomorphic variants of T-cell malignant lymphoma.
An atypical clinical form of Hodgkin's disease featuring predominant subdiaphragmatic involvement, extensive bone marrow infiltration, fevers, pancytopenia, absence of peripheral lymphadenopathy, and frequently a rapidly progressive course has been described. 1,2 This syndrome has been associated with various histologic subtypes of Hodgkin's disease, most commonly lymphocytic de pletion and mixed cellularity. 2,3 Performance of bone marrow aspiration and biopsy has been recommended in patients with clinical features suggestive of this syn drome, inasmuch as diagnostic information obtained with use of this procedure may obviate the need for laparotomy. 2 In this report, we describe a patient with clinical fea tures and bone marrow findings consistent with an atyp ical clinical form of Hodgkin's disease but in whom
subsequent lymph node biopsy specimens were consis tent with a diagnosis of a peripheral T-cell lymphoma. The potential implications of these findings are discussed herein.
MATERIAL AND METHODS Bone marrow aspirate smears and biopsy sections were processed by conventional methods and stained with Wright's stain and hematoxylin and eosin, respectively. Hematoxylin and eosin-stained lymph node sections were examined. Frozen sections and air-dried imprint preparations of lymph node tissue from our patient were analyzed for the presence of antigenic determinants by the use of commercially prepared primary monoclonal antibodies Leu-1, Leu-2a, and Leu-3a (Beckton Dickin son Monoclonal Antibody Center, Sunnyvale, California) and B-1 (Coulter Electronics, Inc., Hialeah, Florida). In a two-step immunostaining method, goat-antimouse peroxidase-conjugated serum (TACO, Inc., Burlingame, California) was used. Affinity column purified F(ab')2 antisera against human κ and λ immunoglobulin light chains (goat peroxidase-conjugated, TAGO, Inc.) were also used on the frozen sections.
*Mayo Graduate School of Medicine, Rochester, Minnesota. Present address: Charlottesville, Virginia. tMayo Graduate School of Medicine, Rochester, Minnesota. Present address: Akron, Ohio. Address reprint requests to Dr. R. L. Phyliky, Division of Hematology, Mayo Clinic, Rochester, MN 55905. Mayo Clin Proc 61:68-71, 1986
68
Mayo Clin Proc, January 1986, Vol 61
T-CELL LYMPHOMA SIMULATING HODGKIN'S DISEASE
69
REPORT OF CASE A 44-year-old woman had a 2-month history of fevers and sweats. Physical examination revealed hepatomegaly, shotty right inguinal nodes, and a systolic heart murmur. Results of blood studies disclosed a hemoglobin concentration of 6.2 g/dl, and a complete blood cell count revealed a leukocyte count of 2,100/mm 3 and a platelet count of 112,000/mm 3 . The differential leukocyte count showed 69% polymorphonuclear cells, 8% bands, 1 7% lymphocytes, 5% monocytes, and 1 % myelocytes. The reticulocyte count was 0.8%, a direct antiglobulin (Coombs') test was negative, a peripheral blood smear lacked diagnostic features, and levels of serum vitamin B12 and folate were within normal limits. Serum protein electrophoresis revealed a low albumin level (1.58 g/dl) but a normal 7-globulin level. Immunoelectrophoresis studies of serum and urine showed no monoclonal proteins. The serum calcium level was 7.4 mg/dl (normal range, 8.9 to 10.1 mg/dl), and results of liver function tests were as follows: serum alkaline phosphatase, 397 U/liter (normal range, 76 to 196 U/liter); serum aspartate aminotransferase, 59 U/liter (normal range, 12 to 31 U/liter); and serum total and direct bilirubin, normal. Multiple blood cultures for fungi and bacteria were negative. Roentgenograms of the chest revealed normal findings. Computed tomographic scans of the abdomen at this time disclosed retroperitoneal lymphadenopathy and also hepatosplenomegaly.
Fig. 1. Bone marrow biopsy specimen, showing neoplastic giant cells with multiple nuclear lobes and macronucleoli, features initially interpreted as diagnostic of Hodgkin's disease. (Hematoxylin and eosin; x640.)
A bone marrow aspirate was nondiagnostic. A bone marrow biopsy specimen showed moderate hypercellularity, focal myelofibrosis, and diffuse infiltration by lymphocytes and atypical large cells, including some multinucleated neoplastic giant cells (Reed-Sternberg cells) (Fig. 1). These findings were thought to be diagnostic of Hodgkin's disease. Biopsy of a slightly enlarged right inguinal lymph node, however, revealed a lymphomatous process that had both morphologic and immunologic features of a pleomorphic (T-cell) non-Hodgkin's neoplasm. The nodal architecture was only partially effaced, and the paracortex was selectively replaced by an abnormal, heterogeneous proliferation of cells (Fig. 2 A). Highmagnification microscopy revealed a continuum of abnormal lymphoid cells, between tumor giant cells with multilobated nuclei and multiple nucleoli and atypical small lymphocytes with irregular, complex nuclear membranes (Fig. 2 ß). The atypia of the small lymphocytic mil ieu that surrounded the tumor giant eel Is was considered not consistent with Hodgkin's disease. Immunostaining suggested the process to be of T-cell na-
ture. In both frozen sections and air-dried imprint preparations, 90% of the cells in the zones of neoplastic involvement, including the large cells, stained for Leu-1 (pan-T-cell) antigen. In the frozen-section preparations, the neoplastic regions stained predominantly (80 to 90%) for Leu-3a (helper/inducer) antigen, whereas only about 10% stained for Leu-2a (suppressor/cytotoxic) antigen and 10% stained for B-1 (pan-B-cell) antigen, κ and λ light chains were demonstrated in equal cellular dis tributions, almost exclusively in the benign portions of the lymph node. The patient's diagnosis was revised to diffuse mixed-type lymphoma, pleomorphic variant, of apparent T-cell immunotype. The patient received one course of multiple-agent chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone), but liver failure ensued and she died within 6 weeks after diagnosis. Autopsy revealed advanced lymphomatous involvement of the liver, spleen, abdominal lymph nodes, and bone marrow. The pattern of splenic involvement by lymphoma—namely, dispersed sinusoidal infiltration—was more consistent
70
T-CELL LYMPHOMA SIMULATING HODGKIN'S DISEASE
Mayo Clin Proc, January 1986, Vol 61
Fig. 2. A, Inguinal lymph node biopsy specimen, showing partial preservation of normal functional cellular components and paracortical zones of heterogeneous neoplastic cellularity (arrows). (Hematoxylin and eosin; x40.) B, Higher-magnification appearance of neoplastic paracortical process, with giant cells surrounded by atypical mononuclear forms. Note that even medium and small-sized lymphocytes contain complex, irregularly shaped nuclei, in contrast to benign, normal-appearing lymphoid background characteristic of Hodgkin's disease. (Hematoxylin and eosin; x640.)
with non-Hodgkin's (T-cell) lymphoma than with Hodgkin's disease, which is characterized by expansive, cohesive tumorous nodules. DISCUSSION Peripheral T-cell lymphoma 4 is a recently recognized, immunologically defined grouping of malignant lymphomas of T-cell origin that has been designated variously as T-immunoblastic sarcoma, 5 node-based T-cell lymphoma, 5 T-zone lymphoma, c> pleomorphic lymphoma, 7 lymphoepithelioid cell lymphoma, 5 and multilobated T-cell lymphoma. 8 A subset of patients with this condition have a distinct clinicopathologic entity called adult T-cell leukemia-lymphoma that has been associated with the human T-cell leukemia virus I. 9 "' 1 Clusters of adult T-cell leukemia-lymphoma have been described in Japan, the Caribbean, and southeastern United States. Clinically, patients with peripheral T-cell lymphomas often have advanced disease and an aggressive course. A
median duration of survival of less than 12 months (mean, 10.9 months) has been reported. 1 2 ' 3 Histologically, peripheral T-cell lymphomas are characterized by a diffuse pleomorphic lymphoid infiltrate composed of small lymphoid cells with irregular hypersegmented nuclei and large lymphoid cells that have abundant clear cytoplasm and round nuclei with prominent nucleoli and striking multilobulation. 1 4 Immunologie studies reveal the T-cell nature of these neoplastic cells. Increased vascularity and compartmentalization are other features that have been noted. The appearance of the large neoplastic cells can be confused with that of Reed-Sternberg cells. Although the neoplastic T-lymphocytes usually have nuclei with greater lobulations and smaller nucleoli than those of Reed-Sternberg cells, these distinguishing features can be exceedingly subtle. The pleomorphic nature of the neoplastic lymphoid infiltrate in peripheral T-cell lymphomas, a feature usually lacking in Hodgkin's disease,
Mayo Clin Proc, January 1986, Vol 61
may be difficult to appreciate in small extranodal biopsy samples.15 As shown by the case presented herein, the clinical manifestations in patients with peripheral T-cell lymphomas can resemble an atypical clinical form of Hodgkin's disease. Thus, Hodgkin's disease can be incorrectly diagnosed in patients with peripheral T-cell lymphomas on the basis of bone marrow biopsy findings alone. The correct classification of the neoplastic lymphoid process in such patients can have important therapeutic, prognostic, and epidemiologic implications. Therefore, we recommend that physicians resist the temptation to accept a diagnosis of Hodgkin's disease based only on bone marrow biopsy findings. A careful search for lymphadenopathy should be made in the hope of obtaining nodal tissue for histologic and immunologic examinations. If the medical condition of the patient precludes a surgical procedure, immunologic studies of the bone marrow tissue to determine whether the neoplastic cells are of T-cell origin can provide additional helpful information. ACKNOWLEDGMENT We thank Wendy K. Hollingsworth for secretarial assistance with the original manuscript. REFERENCES 1.
2.
Longcope W T : Hodgkin's disease. In The Oxford Medicine. Part 1, Vol 4. Edited by HA Christian. New York, Oxford University Press, 1949, pp 1-44 Neiman RS, Rosen PJ, Lukes R): Lymphocyte-depletion Hodgkin's disease: a c l i n i c o p a t h o l o g i c a l entity. N EngI ) Med 288:751-755, 1973
T-CELL LYMPHOMA SIMULATING HODGKIN'S DISEASE
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14. 15.
71
Sobrinho-Simoes M , Paiva ME, Goncalves V, Saldanha C, Vaz Saleiro J, Serrao D: Hodgkin's disease with predominant i n fradiaphragmatic involvement and massive invasion of the bone marrow: a necropsic study of nine cases. Cancer 52:1927-1932, 1983 Waldron JA, Leech JH, Glick A D , FlexnerJM, Collins RD: Malignant lymphoma of peripheral T-lymphocyte origin: i m m u nologic, pathologic, and clinical features in six patients. Cancer 40:1604-1617, 1977 Collins RD, Waldron JA, Glick A D : Results of multiparameter studies of T-cell l y m p h o i d neoplasms. A m J Clin Pathol 72:699-707, 1979 Lennert K: Malignant Lymphomas Other Than Hodgkin's Disease: Histology, Cytology, Ultrastructure, Immunology. New York, Springer-Verlag, 1978 WatanabeS, NakajimaT, Shimosato Y, ShimoyamaM, MinatoK: T-cell malignancies: subclassification and interrelationship. JpnJ Clin Oncol 9 Suppl:423-442, 1979 Pinkus GS, Said JW, Hargreaves H: Malignant lymphoma, T-cell type: a distinct morphologic variant with large multilobated nuclei, with a report of four cases. Am J Clin Pathol 72:540-550, 1979 Gallo RC, de The GB, Ito Y: Kyoto workshop on some specific recent advances in h u m a n t u m o r v i r o l o g y . Cancer Res 41:4738-4739, 1981 Catovsky D, Rose M , Goolden A W G , White JM, Bourikas G, Brownell A I , Blattner W A , Greaves MF, Galton DAG, McCIuskey DR, Lampert I, Ireland R, Bridges JM, Gallo RC: Adult T-cell lymphoma-leukaemia in Blacks from the West Indies. Lancet 1:639-643, 1982 Blayney D W , Jaffe ES, Blattner W A , CossmanJ, Robert-Guroff M , Longo DL, Bunn PA Jr, Gallo RC: The human T-cell leukemia/ lymphoma virus associated with American adult T-cell leukemia/ lymphoma. Blood 62:401-405, 1983 Brisbane JU, Berman LD, Neiman RS: Peripheral T-cell lymphoma: a clinicopathologic study of nine cases. A m J Clin Pathol 79:285-293, 1983 GreerJP, YorkJC, CousarJB, Mitchell RT, FlexnerJM, Collins RD, Stein RS: Peripheral T-cell lymphoma: a clinicopathologic study of 42 cases. J Clin Oncol 2:788-798, 1984 N e i m a n RS: I m m u n o b l a s t i c sarcoma. A m J Surg Pathol 6:755-760, 1982 Wright D H , Isaacson PG: Biopsy Pathology of the Lymphoreticular System. Baltimore, Williams & Wilkins Company, 1983, pp 215-219