Aust. N.Z. J. Med. (1976), 6, pp. 463-466 CASE REPORT
-
Thymus with B Lymphocytes in Chronic Lymphocytic Leukaemia p. 6 . Adams and I. A. Cooper From lrnrnunobiology Research Section, Haernatology Research Unit, Cancer Institute, Melbourne
Summaw: Thymus with B lymphocytes in chronic lymphocytic leukaemia. P. B. Adarns and I. A. Cooper, Aust. N.Z. J. Med., 1976, 6, pp. 463-466.
A 67-year-old man with a diagnosis of chronic lymphocytic leukaemia died suddenly following a coronary occlusion. Peripheral blood lymphocytes labelled with fluorescein conjugated polyvalent antisera to immunoglobulin and immunoglobulin G, and failed to label with absorbed antith ymoc yte serum. At necropsy, a large thymic tumour, and enlarged mediastinal lymph nodes also contained immunoglobulin G bearing B lymphocytes. The paradoxical finding of B lymphocytes with monoclonal surface immunoglobulin in a thymic mass is most unusual in chronic lymphocytic leukaemia.
Many studies suggest that with rare exceptions the leukaemic cells of chronic lymphocytic leukaemia (CLL) are B lymphocytes bearing surface immunoglobulin which is readily detectable with fluorescein conjugated antisera. These cells replace normal architecture in bone marrow, lymph nodes and spleen and infiltrate a wide variety of tissues. Thymic infiltration with leukaemic cells in older adults is an unusuaI occurrence, as the thymus gland reaches a maximum size at puberty and by progressive involution becomes an insignificant, fibrofatty remnant in old age. The finding of a mass in the anterior mediastinum on chest X-ray and at necropsy, in a 67-year-old man with a diagnosis of CLL, raised the possibility of a second malignancy, perhaps arising in the thymus. Histology and studies of cell surface markers indicated that the mass represented a thymus gland composed of B lymphocytes Correspondence; Dr. Peter B. Adams. Cancer Institute, 481 Little Lonsdale St., Melbourne, Victoria 3000 Accepted for publication: 26 May, 1976
with the same characteristics as the leukaemic cells present in peripheral blood and lymph node. Case Report
In August 1974 a 67-year-old retired hairdresser presented to his local practitioner with a cervical lump which had been present for three months. On examination, generalized lymphadenopathy and marked hepatosplenomegaly were noted. Congenital pulmonary stenosis and ischaemic heart disease had been diagnosed in 1960, but no signs of cardiac failure were found at this presentation. A blood count showed a haemoglobin of 12.8 g/100 ml, white cell count of 185,000/mm3 and platelet count of 85,000/mm3. Ninetyseven per cent of the leucocytes were small, round lymphocytes with a high nuclear-cytoplasmic ratio and a round nucleus with no visible nucleoli (Fig. 1). Aspiration from the right posterior iliac crest yielded bone marrow particles with an infiltrate of small, mature lymphoid cells, and occasional less well differentiated cells with clefted nuclei and prominent nucleoli. A gallium (67Ga)scan showed a moderate uptake in the hilar region of the lungs. Chest X-ray and tomograms indicated a greatly enlarged heart and a soft tissue mass compressjng the lower end of the trachea on the right side and displacing it to the left. This mass contained some calcium and the radiologist considered that it could represent an aneurysm of the ascending aorta. No enlarged mediastinal or hilar lymph nodes were detected. The patient was treated with chlorambucil, prednisolone and vincristine sulphate, together with leucapheresis on four occasions using a Continuous Flow Blood Cell Separator (Celltrifuge)
F I G U R E 1. Chronic lyrnphocytic leukaemia cells from blood stained with Jenner-Giemsa.
464
FIGURE 3. FIGURE 2.
VOL. 6 , NO. 5
ADAMS A N D COOPER
Thymic tumour.
Thymic tumour mass at necropsy.
S!). The leucocyte (American Instrument Co., Maryland, U count was reduced to 42,000/mm3 with a moderate diminution in the size of spleen, liver and peripheral lymph nodes. Four weeks later he was admitted with fever, malaise, shivering episodes, peripheral oedema, dyspnoea on slight exertion and increased generalized lymphadenopathy. Intravenous antibiotics and diuretics were commenced, but his condition deteriorated during the next 24 hours and he collapsed suddenly and died. At necropsy, pulmonary stenosis and cardiac ienlargement due to dilatation and hypertrophy were confirmed. The first 2 cm of the anterior descending branch of the left coronary artery showed complete occlusion due to a recent thrombosis. No macroscopic or light microscopic evidence of cardiac infarction, and no aortic or other great vessel aneurysm were present. The liver (2400 g) and spleen (800 g) were enlarged, and lymph nodes up to 2 cm in diameter and replaced by white tumour tissue were found in the lower para-aortic area, porta hepatis and hilar regions of the lungs. A large, pale yellow encapsulated mass (1 1 x 10 x 5 cm) weighing 200 g was found in the anterior mediastinum, occupying the site of the thymus (Fig. 2). Scme discrete lymph nodes were present adjacent to it. The mass presented a smooth glistening surface and when cut revealed a diffuse infiltration of greyish white tumour. On the basis of the macroscopic appearance, shape and position, the mass was considered to be thymus. Sections of the mediastinal mass showed a lymphocytic tumour beneath a t.hin capsule, the bulk of which consisted of small, round, mature cells (Fig. 3). No clearly defined Hassall’s corpuscles or epithelioid cells were observed, and no calcium deposits were present. The normal structure of the mediastinal lymph nodes was also replaced by round mature c d s (Fig. 4). The vertebral bone marrow was pale and diffusely infiltrated by well differentiated lymphocytes. A light infiltrate of lymphocytes was found in the epicardium, perivascular tissue of the myocardium and in the alveolar septa and perivascular connective tissue of the lungs. Focal collections of small lymphocytes were scattered .through the kidneys. Special Investigations When cultivated with phytohaemagglutinin and pokeweed mitogen according to the method of Fitzgerald’, peripheral blood lymphocytes did not respond at three days, and only a small response to both mitogens was observed at six days.
Tritiated thymidine incorporation in unstimulated cultures was reduced in comparison with lymphocytes from normal healthy individuals. Surface immunoglobulins were demonstrated by direct immunofluorescence using fluorescein-conjugated antisera (Meloy Laboratories, Springfield, Virginia) as described previously.’ An antithymocyte serum absorbed with B (CLL) cells was used to identify T lymphocytes.’ On four separate occasions during August 1974, peripheral blood lymphocyte populations were found to consist almost entirely of cells labelling with a dense pattern of intense fluorescence with antisera to polyvalent immunoglobulin and immunoglobulin G (Table 1). Almost identical results were obtained with a Celltrifuge sample, and with lymphocytes prepared from enlarged lymph nodes and thymic tumour obtained at necropsy. Discussion
The unexpected necropsy finding of a mass in the thymic region of an elderly patient with CLL, prompted further studies regarding the characteristics of the “thymic” cells and the
F I G U R E 4. Mediastinal lymph node removed at necropsy. Portion of the capsule is visible at bottom.
OCTOBER,
1976
THYMIC INVOLVEMENT BY "B" TABLE 1
lmmunofluorescence identification of lymphocytes
Cell source
Peripheral blood Celltrifuge sample Lymphnode
% of cells labelling with fluorescein conjugatcd Normal antisera value (%) Polyvalent IgM IgG IgA IgD Antithymocyte Ig
1
0
15-25* 70-85
100
-
100
0
100
0
0
2-35.
98
0
98
0
0
99
0
< I
-
Thymus with B Lymphocytes in Chronic Lymphocytic Leukaemia p. 6 . Adams and I. A. Cooper From lrnrnunobiology Research Section, Haernatology Research Unit, Cancer Institute, Melbourne
Summaw: Thymus with B lymphocytes in chronic lymphocytic leukaemia. P. B. Adarns and I. A. Cooper, Aust. N.Z. J. Med., 1976, 6, pp. 463-466.
A 67-year-old man with a diagnosis of chronic lymphocytic leukaemia died suddenly following a coronary occlusion. Peripheral blood lymphocytes labelled with fluorescein conjugated polyvalent antisera to immunoglobulin and immunoglobulin G, and failed to label with absorbed antith ymoc yte serum. At necropsy, a large thymic tumour, and enlarged mediastinal lymph nodes also contained immunoglobulin G bearing B lymphocytes. The paradoxical finding of B lymphocytes with monoclonal surface immunoglobulin in a thymic mass is most unusual in chronic lymphocytic leukaemia.
Many studies suggest that with rare exceptions the leukaemic cells of chronic lymphocytic leukaemia (CLL) are B lymphocytes bearing surface immunoglobulin which is readily detectable with fluorescein conjugated antisera. These cells replace normal architecture in bone marrow, lymph nodes and spleen and infiltrate a wide variety of tissues. Thymic infiltration with leukaemic cells in older adults is an unusuaI occurrence, as the thymus gland reaches a maximum size at puberty and by progressive involution becomes an insignificant, fibrofatty remnant in old age. The finding of a mass in the anterior mediastinum on chest X-ray and at necropsy, in a 67-year-old man with a diagnosis of CLL, raised the possibility of a second malignancy, perhaps arising in the thymus. Histology and studies of cell surface markers indicated that the mass represented a thymus gland composed of B lymphocytes Correspondence; Dr. Peter B. Adams. Cancer Institute, 481 Little Lonsdale St., Melbourne, Victoria 3000 Accepted for publication: 26 May, 1976
with the same characteristics as the leukaemic cells present in peripheral blood and lymph node. Case Report
In August 1974 a 67-year-old retired hairdresser presented to his local practitioner with a cervical lump which had been present for three months. On examination, generalized lymphadenopathy and marked hepatosplenomegaly were noted. Congenital pulmonary stenosis and ischaemic heart disease had been diagnosed in 1960, but no signs of cardiac failure were found at this presentation. A blood count showed a haemoglobin of 12.8 g/100 ml, white cell count of 185,000/mm3 and platelet count of 85,000/mm3. Ninetyseven per cent of the leucocytes were small, round lymphocytes with a high nuclear-cytoplasmic ratio and a round nucleus with no visible nucleoli (Fig. 1). Aspiration from the right posterior iliac crest yielded bone marrow particles with an infiltrate of small, mature lymphoid cells, and occasional less well differentiated cells with clefted nuclei and prominent nucleoli. A gallium (67Ga)scan showed a moderate uptake in the hilar region of the lungs. Chest X-ray and tomograms indicated a greatly enlarged heart and a soft tissue mass compressjng the lower end of the trachea on the right side and displacing it to the left. This mass contained some calcium and the radiologist considered that it could represent an aneurysm of the ascending aorta. No enlarged mediastinal or hilar lymph nodes were detected. The patient was treated with chlorambucil, prednisolone and vincristine sulphate, together with leucapheresis on four occasions using a Continuous Flow Blood Cell Separator (Celltrifuge)
F I G U R E 1. Chronic lyrnphocytic leukaemia cells from blood stained with Jenner-Giemsa.
464
FIGURE 3. FIGURE 2.
VOL. 6 , NO. 5
ADAMS A N D COOPER
Thymic tumour.
Thymic tumour mass at necropsy.
S!). The leucocyte (American Instrument Co., Maryland, U count was reduced to 42,000/mm3 with a moderate diminution in the size of spleen, liver and peripheral lymph nodes. Four weeks later he was admitted with fever, malaise, shivering episodes, peripheral oedema, dyspnoea on slight exertion and increased generalized lymphadenopathy. Intravenous antibiotics and diuretics were commenced, but his condition deteriorated during the next 24 hours and he collapsed suddenly and died. At necropsy, pulmonary stenosis and cardiac ienlargement due to dilatation and hypertrophy were confirmed. The first 2 cm of the anterior descending branch of the left coronary artery showed complete occlusion due to a recent thrombosis. No macroscopic or light microscopic evidence of cardiac infarction, and no aortic or other great vessel aneurysm were present. The liver (2400 g) and spleen (800 g) were enlarged, and lymph nodes up to 2 cm in diameter and replaced by white tumour tissue were found in the lower para-aortic area, porta hepatis and hilar regions of the lungs. A large, pale yellow encapsulated mass (1 1 x 10 x 5 cm) weighing 200 g was found in the anterior mediastinum, occupying the site of the thymus (Fig. 2). Scme discrete lymph nodes were present adjacent to it. The mass presented a smooth glistening surface and when cut revealed a diffuse infiltration of greyish white tumour. On the basis of the macroscopic appearance, shape and position, the mass was considered to be thymus. Sections of the mediastinal mass showed a lymphocytic tumour beneath a t.hin capsule, the bulk of which consisted of small, round, mature cells (Fig. 3). No clearly defined Hassall’s corpuscles or epithelioid cells were observed, and no calcium deposits were present. The normal structure of the mediastinal lymph nodes was also replaced by round mature c d s (Fig. 4). The vertebral bone marrow was pale and diffusely infiltrated by well differentiated lymphocytes. A light infiltrate of lymphocytes was found in the epicardium, perivascular tissue of the myocardium and in the alveolar septa and perivascular connective tissue of the lungs. Focal collections of small lymphocytes were scattered .through the kidneys. Special Investigations When cultivated with phytohaemagglutinin and pokeweed mitogen according to the method of Fitzgerald’, peripheral blood lymphocytes did not respond at three days, and only a small response to both mitogens was observed at six days.
Tritiated thymidine incorporation in unstimulated cultures was reduced in comparison with lymphocytes from normal healthy individuals. Surface immunoglobulins were demonstrated by direct immunofluorescence using fluorescein-conjugated antisera (Meloy Laboratories, Springfield, Virginia) as described previously.’ An antithymocyte serum absorbed with B (CLL) cells was used to identify T lymphocytes.’ On four separate occasions during August 1974, peripheral blood lymphocyte populations were found to consist almost entirely of cells labelling with a dense pattern of intense fluorescence with antisera to polyvalent immunoglobulin and immunoglobulin G (Table 1). Almost identical results were obtained with a Celltrifuge sample, and with lymphocytes prepared from enlarged lymph nodes and thymic tumour obtained at necropsy. Discussion
The unexpected necropsy finding of a mass in the thymic region of an elderly patient with CLL, prompted further studies regarding the characteristics of the “thymic” cells and the
F I G U R E 4. Mediastinal lymph node removed at necropsy. Portion of the capsule is visible at bottom.
OCTOBER,
1976
THYMIC INVOLVEMENT BY "B" TABLE 1
lmmunofluorescence identification of lymphocytes
Cell source
Peripheral blood Celltrifuge sample Lymphnode
% of cells labelling with fluorescein conjugatcd Normal antisera value (%) Polyvalent IgM IgG IgA IgD Antithymocyte Ig
1
0
15-25* 70-85
100
-
100
0
100
0
0
2-35.
98
0
98
0
0
99
0
< I
