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Extramedullary plasmacytoma IgG type I presenting as mediastinal syndrome
Brit. 3. Dis. Chest (1974) 68, 65
EXTRAMEDULLARY PLASMACYTOMA TYPE I PRESENTING AS MEDIASTINAL SYNDROME R. M. GUPTA, Institute
D. C.
of Medical
ROY, I. M.
GUPTA
Sciences, Banaras Hindu
IgG
AND S. KHANNA University,
India
MYELOMA presenting primarily as an extra-osseous tumour, though rare, is well recorded (Hellwig 1943; Churg & Gordon 1950; Hayes et al. 1952 ; Dolin & Dewar 1956; Wiltshaw 1971). In recent years extramedullary plasmacytoma has merited consideration in the differential diagnosis of pulmonary disease (Childress & Adie rg5g ; Favis et al. rg6o ; Herskovics et al. r 965 ; Gabriel r 965; Durant et al. rg66), unexplained lymphadenopathy (Simon & Eidlow 1950; Rowlands & Shaw 1954; Nelson & Lyons r 957; Edwards & Zawadski 1967; Singh 1968) and skin lesions (Hayes et al. 1g5r ; Dolin & Dewar 1956; Johnson & Taylor 1970). The case is recorded because of an unusual trio of chest symptoms, massive cervical lymphadenopathy and skin infiltration in a young adult.
Case Report An 18-year-old Indian man was admitted to Sir Sunder-la1 Hospital on rg June rg6g with severe dyspnoea, unproductive cough and fullness on both sides of the chest for 2 months and with swelling in the neck and both axillae for 4 months. Back pain, diminished appetite, occasional fever and marked weakness had been present for 6 months. He was very breathless, slightly cyanosed and had generalized muscular wasting with massive bilateral enlargement of cervical and axillary lymph nodes, which were freely mobile and not tender. A few glands were also palpable in the inguinal region. Pitting oedema and a few purplish macules and venous engorgement were present over the chest wall. Movements and vocal fremitus were diminished on the left side. Auscultation revealed dullness, with masking of the liver, indicative of massive right-sided pleural effusion. The left side was normal. The liver was palpable 2 fingerbreadths below the left costal margin, non-tender and firm. Neurological examination of the patient was normal A radiographic survey of the skeleton failed to reveal bony lesions. Deep penetration radiographs of the chest showed some destruction of the first, second and third ribs on the right side, suggestive of ‘nodal reticulum cell sarcoma’ with secondary involvement of the ribs or of Ewing’s sarcoma. There was homogenous opacity in the right hemithorax with a shift of the mediatinum to the left. A provisional diagnosis of Hodgkin’s disease with mediastinal involvement was made. (Received for publication
April
1972)
66
GUPTA
ET
AL.
The total white blood count was 20 ooo/mm3, with 98% polymorphs and lymphocytes. No immature cells were seen. The peripheral blood film showed normocytic normochromic red cells and platelets were adequate. 2%
FIG.
I.
Section from a lymph node showing plasmoblasts in large numbers replacing lymphoid tissue. A few polymorphs can also be seen. H & E. x 560 829
FIG.
2.
MYELOMA
Serum paper electrophoresis
BEFORE
normal
TREATMENT
showing the M spike in the y-1 region,
The ESR was 35 mm in the first hour (Wintrobe). The haemoglobin was I 1-5 g/100 ml and the haematocrit 36%. The sternal smear showed a slight increase in cellularity, and M : E ratio of 5 : I, a normoblastic reaction, and no
EXTRAMEDULLARY
FIG. 3. Serum
PLASMACYTOMA
micro-immunoelectrophoresis normal
Pleural
FIG.
4. Paper
Fluid
electrophoretic
showing reduplication serum; Pt, test serum.
control
829
Kailash
analysis
Id.
Mycloma
of pleural
of the
fluid
showing
IgG
arc.
C, pot pled
n
the
y-1 spike.
abnormal cells were seen. The serum calcium was IO mg/r oo ml, phosphorus 3-5 mg/roo ml, alkaline phosphatase 1.5 Bodanski units. VDRL was negative and CSF examination was normal. Tests for Bence-Jones proteinuria and albuminuria were negative.
68
GUPTA
ET
AL.
(4
FIG.
5. Micro-immunoelectrophoresis
of pleural type
fluid I
(p)
showing
the
M
protein
tc ) be IgG
The histopathology of the lymph node removed from the neck showed a plae ;ma cell myeloma with plasmoblasts predominant and replacing almost the entire normal lymphoid tissue (Fig. I). Biopsy from the macular lesions showing mature on the chest revealed non-specific chronic inflammation, plas Ima cells. Iliac crest biopsy was normal.
EXTRAMEDULLARY
PLASMACYTOMA
69
The total serum proteins were 6.4 g/r00 ml, albumin 3.5 g/roe ml and globulin 2-g g/roe ml. Paper electrophoresisrevealed an M spike in the y-1 region (Fig. 2). Densitometric analysis showed albumin 4g%, a-globulins 3%, a-2-globulins 8%, /3-globulins 8% and y-globulin 32% of total proteins. Micro-electrophoresis revealed the M protein to be IgG type I (Figs 3, 4). The pleural aspirates contained plasma cells which appeared to be more mature than those seen in the lymph node. Biochemical examination showed protein 2.4 g/r oo ml. The M spike was seen in the 01-1 region (Fig. 5A). Densitrometric analysis showed albumin 33%, a- r-globulin 7 %, ol-n-globulin I I o/o) P-globulin I I o/o and y-globulin 33% of total protein. Micro-immunoelectrophoresis revealed M protein of IgG class (Fig. 5B). The patient was given radiotherapy to which he responded dramatically; his glands subsided and skin papules disappeared. He left the hospital against medical advice, however, and has not reported since. Discussion Pleural involvement in myeloma is very rare. Herskovics et al. (I 965)) reviewing cases from the Mayo Clinic, record only 33 cases of myeloma of the chest; pleural effusion was seen in only 2 of these cases. Gabriel (1965) reported a case of pulmonary plasmocytoma where the patient finally developed a pleural effusion containing plasma cells. In this case M protein was present in higher concentration in the pleural fluid than in the serum. Innes and Newall (rg6r), reviewing 188 cases of myeloma, record only a single case of lung involvement, and autopsy revealed an extraordinary sheath-like mass of plasma cells lining the pleural cavity, but the mediastinum was spared. Durant et al. (rg66), discussing unusual presentations of myeloma, record pleural effusion in 2 cases. Edwards and Zawadski ( 1967) reported 6 cases of extramedullary plasmocytoma; pleural effusion with demineralization of the ribs without lytic lesions was seen in only I case. Whether the lesions in the ribs in our patient were primary is difficult to assess. However, the absence of generalized medullary involvement, indicated by a normal smear and iliac crest biopsy, suggests the contrary. Primary massive lymph node enlargement is rare and misleading in myeloma. Simon and Eidlow (1950) noted enlargement of the nodes several years before clinical manifestations of myeloma in I patient. Rowlands and Shaw (1954) reported a case simulating Hodgkin’s disease, very similar to ours. Nelson and Lyons (1957) noted recurrent axillary lymphadenopathy after resection. Edwards and Zawadski (1967) reported the occurrence of gross lymphadenopathy in I -2 y. of their cases. Singh ( I 968) cited the occurrence of massive lymphadenopathy in 5 of 15 cases of the Victor-Odelberg-Johnson syndrome from the world literature, including their own case. Skin infiltration is another rare feature of myeloma. Hayes et al. (rg52), discussing 182 cases of extra-osseous myeloma, found skin lesions in only 4 cases. Dolin and Dewar (1956) recorded skin involvement in 2 of 126 cases of extramedullary plasmacytoma. Durant et al. (1966) reported 2 cases of
GUPTA
70
ET
AL.
skin infiltration mimicking cutaneous neoplasms. In I of the 2 cases of skin involvement reported by Edwards and Zawadski (1967) purplish nodules, which responded well to radiation therapy, were noted on the chest, abdomen and thigh. In the present case purplish papules, present on the chest wall in relation to the involved ribs, responded readily to radiation therapy, though the histology of the skin lesions was equivocal for myeloma. The outstanding features of our case are massive lymphadenopathy, pleural effusion and skin involvement combined in a young man; each of these lesions in itself is rare in myeloma. Summary
The case is reported of a young man with extramedullary plasmacytoma presenting with massive cervical lymphadenopathy, pleural effusion and purplish papules on the chest wall. Histopathology of a lymph node from the neck revealed a plasmacytoma. Immunochemical studies on serum and pleural fluid showed M paraprotein of IgG type I.
REFERENCES
CHILDRESS,
W. & ADIE, G. C. (I 959) Plasma cell tumours of mediastinum
surg., ‘9, 794.
CHURG, J. & GORDON, A. poietic system. An. 3. DOLIN, S. & DEWAR, J. P. DURANT, J. R., BARRY, W. Lzncet, EDWARDS,
Path.,
myeloma.
Lesions of the extra-osseous
hema-
20, 934.
(1956) Extramedullary plasmacytoma. Am. 3. Path., 32, 83. E. & LEARNER, N. (1966) The changing face of multiple myeloma.
i, I 19.
G. A report FAVIS, E. A., problem GABRIEL, S. case.
J. (1950) Multiple clin.
and lung. 3. thoruc.
A. & ZAWADSKI, of six cases. Am. KERMAN, H. D. in the diagnosis (1965) Multiple
Db
Chest,
47,
Z. A. (1967) Extraosseous
3.
Med.,
43,
lesions in plasma
cell myeloma.
194.
& SCHILDECKER, W. (1960) Multiple myeloma manifested as a of pulmonary disease. Am. 3. Med., 28, 323. myeloma presenting as pulmonary infiltration. Report of a
123.
I&YES, D. W., BENNETT, W. A. & HECK, F. J. (1952) Extramedullary lesions in multiple myeloma. Review of the literature and pathologic studies. Archs Path., 53, 262. HELL~V~G, C. A. (1943) Extramedullary plasma cell tumours as observed in various locations. Archs
Path.,
36,
95.
HERSKOVICS, T., ANDERSON, H. A. & BAYRD, E. D. Presentation of 2 I cases and review of literature. Dir. INNES, J. & NEWALL, J. (1961) Myelomatosis. Lancet, i, JOHNSON, W. H. jun. & TAYLOR, B. G. (1970) Solitary skin. A review of world literature and report of an NELSON, M. G. & LYONS, A. R. (1957) Plasmacytoma 1275.
(1965) Chest, 239.
Intrathoracic 47,
plasmacytoma.
I.
extramedullary plasmacytoma of the additional case. Cancer, N.Y., 26, 65. of lymph glands. Cancer, .N.Y., JO,
ROWLANDS, B. & SHAW, N. (1954) Extramedullary plasmacytoma. Br. med. J., i, 1302. SIMON, M. A. & EIDLOW, S. (1950) Plasmacytoma of lymphnode. Report of a case with multiple myeloma. .New Engl. 3. Med., 242, 335. SINGH, M. N. (1968) Lymphadenopathy, peripheral neuropathy and bone lesions. Bull. All-India Inst. med. Sci., 2, 166. WILTSHAW, E. (1971) Extramedullary plasmacytoma. Br. med. J., ii, 327.
EXTRAMEDULLARY PLASMACYTOMA TYPE I PRESENTING AS MEDIASTINAL SYNDROME R. M. GUPTA, Institute
D. C.
of Medical
ROY, I. M.
GUPTA
Sciences, Banaras Hindu
IgG
AND S. KHANNA University,
India
MYELOMA presenting primarily as an extra-osseous tumour, though rare, is well recorded (Hellwig 1943; Churg & Gordon 1950; Hayes et al. 1952 ; Dolin & Dewar 1956; Wiltshaw 1971). In recent years extramedullary plasmacytoma has merited consideration in the differential diagnosis of pulmonary disease (Childress & Adie rg5g ; Favis et al. rg6o ; Herskovics et al. r 965 ; Gabriel r 965; Durant et al. rg66), unexplained lymphadenopathy (Simon & Eidlow 1950; Rowlands & Shaw 1954; Nelson & Lyons r 957; Edwards & Zawadski 1967; Singh 1968) and skin lesions (Hayes et al. 1g5r ; Dolin & Dewar 1956; Johnson & Taylor 1970). The case is recorded because of an unusual trio of chest symptoms, massive cervical lymphadenopathy and skin infiltration in a young adult.
Case Report An 18-year-old Indian man was admitted to Sir Sunder-la1 Hospital on rg June rg6g with severe dyspnoea, unproductive cough and fullness on both sides of the chest for 2 months and with swelling in the neck and both axillae for 4 months. Back pain, diminished appetite, occasional fever and marked weakness had been present for 6 months. He was very breathless, slightly cyanosed and had generalized muscular wasting with massive bilateral enlargement of cervical and axillary lymph nodes, which were freely mobile and not tender. A few glands were also palpable in the inguinal region. Pitting oedema and a few purplish macules and venous engorgement were present over the chest wall. Movements and vocal fremitus were diminished on the left side. Auscultation revealed dullness, with masking of the liver, indicative of massive right-sided pleural effusion. The left side was normal. The liver was palpable 2 fingerbreadths below the left costal margin, non-tender and firm. Neurological examination of the patient was normal A radiographic survey of the skeleton failed to reveal bony lesions. Deep penetration radiographs of the chest showed some destruction of the first, second and third ribs on the right side, suggestive of ‘nodal reticulum cell sarcoma’ with secondary involvement of the ribs or of Ewing’s sarcoma. There was homogenous opacity in the right hemithorax with a shift of the mediatinum to the left. A provisional diagnosis of Hodgkin’s disease with mediastinal involvement was made. (Received for publication
April
1972)
66
GUPTA
ET
AL.
The total white blood count was 20 ooo/mm3, with 98% polymorphs and lymphocytes. No immature cells were seen. The peripheral blood film showed normocytic normochromic red cells and platelets were adequate. 2%
FIG.
I.
Section from a lymph node showing plasmoblasts in large numbers replacing lymphoid tissue. A few polymorphs can also be seen. H & E. x 560 829
FIG.
2.
MYELOMA
Serum paper electrophoresis
BEFORE
normal
TREATMENT
showing the M spike in the y-1 region,
The ESR was 35 mm in the first hour (Wintrobe). The haemoglobin was I 1-5 g/100 ml and the haematocrit 36%. The sternal smear showed a slight increase in cellularity, and M : E ratio of 5 : I, a normoblastic reaction, and no
EXTRAMEDULLARY
FIG. 3. Serum
PLASMACYTOMA
micro-immunoelectrophoresis normal
Pleural
FIG.
4. Paper
Fluid
electrophoretic
showing reduplication serum; Pt, test serum.
control
829
Kailash
analysis
Id.
Mycloma
of pleural
of the
fluid
showing
IgG
arc.
C, pot pled
n
the
y-1 spike.
abnormal cells were seen. The serum calcium was IO mg/r oo ml, phosphorus 3-5 mg/roo ml, alkaline phosphatase 1.5 Bodanski units. VDRL was negative and CSF examination was normal. Tests for Bence-Jones proteinuria and albuminuria were negative.
68
GUPTA
ET
AL.
(4
FIG.
5. Micro-immunoelectrophoresis
of pleural type
fluid I
(p)
showing
the
M
protein
tc ) be IgG
The histopathology of the lymph node removed from the neck showed a plae ;ma cell myeloma with plasmoblasts predominant and replacing almost the entire normal lymphoid tissue (Fig. I). Biopsy from the macular lesions showing mature on the chest revealed non-specific chronic inflammation, plas Ima cells. Iliac crest biopsy was normal.
EXTRAMEDULLARY
PLASMACYTOMA
69
The total serum proteins were 6.4 g/r00 ml, albumin 3.5 g/roe ml and globulin 2-g g/roe ml. Paper electrophoresisrevealed an M spike in the y-1 region (Fig. 2). Densitometric analysis showed albumin 4g%, a-globulins 3%, a-2-globulins 8%, /3-globulins 8% and y-globulin 32% of total proteins. Micro-electrophoresis revealed the M protein to be IgG type I (Figs 3, 4). The pleural aspirates contained plasma cells which appeared to be more mature than those seen in the lymph node. Biochemical examination showed protein 2.4 g/r oo ml. The M spike was seen in the 01-1 region (Fig. 5A). Densitrometric analysis showed albumin 33%, a- r-globulin 7 %, ol-n-globulin I I o/o) P-globulin I I o/o and y-globulin 33% of total protein. Micro-immunoelectrophoresis revealed M protein of IgG class (Fig. 5B). The patient was given radiotherapy to which he responded dramatically; his glands subsided and skin papules disappeared. He left the hospital against medical advice, however, and has not reported since. Discussion Pleural involvement in myeloma is very rare. Herskovics et al. (I 965)) reviewing cases from the Mayo Clinic, record only 33 cases of myeloma of the chest; pleural effusion was seen in only 2 of these cases. Gabriel (1965) reported a case of pulmonary plasmocytoma where the patient finally developed a pleural effusion containing plasma cells. In this case M protein was present in higher concentration in the pleural fluid than in the serum. Innes and Newall (rg6r), reviewing 188 cases of myeloma, record only a single case of lung involvement, and autopsy revealed an extraordinary sheath-like mass of plasma cells lining the pleural cavity, but the mediastinum was spared. Durant et al. (rg66), discussing unusual presentations of myeloma, record pleural effusion in 2 cases. Edwards and Zawadski ( 1967) reported 6 cases of extramedullary plasmocytoma; pleural effusion with demineralization of the ribs without lytic lesions was seen in only I case. Whether the lesions in the ribs in our patient were primary is difficult to assess. However, the absence of generalized medullary involvement, indicated by a normal smear and iliac crest biopsy, suggests the contrary. Primary massive lymph node enlargement is rare and misleading in myeloma. Simon and Eidlow (1950) noted enlargement of the nodes several years before clinical manifestations of myeloma in I patient. Rowlands and Shaw (1954) reported a case simulating Hodgkin’s disease, very similar to ours. Nelson and Lyons (1957) noted recurrent axillary lymphadenopathy after resection. Edwards and Zawadski (1967) reported the occurrence of gross lymphadenopathy in I -2 y. of their cases. Singh ( I 968) cited the occurrence of massive lymphadenopathy in 5 of 15 cases of the Victor-Odelberg-Johnson syndrome from the world literature, including their own case. Skin infiltration is another rare feature of myeloma. Hayes et al. (rg52), discussing 182 cases of extra-osseous myeloma, found skin lesions in only 4 cases. Dolin and Dewar (1956) recorded skin involvement in 2 of 126 cases of extramedullary plasmacytoma. Durant et al. (1966) reported 2 cases of
GUPTA
70
ET
AL.
skin infiltration mimicking cutaneous neoplasms. In I of the 2 cases of skin involvement reported by Edwards and Zawadski (1967) purplish nodules, which responded well to radiation therapy, were noted on the chest, abdomen and thigh. In the present case purplish papules, present on the chest wall in relation to the involved ribs, responded readily to radiation therapy, though the histology of the skin lesions was equivocal for myeloma. The outstanding features of our case are massive lymphadenopathy, pleural effusion and skin involvement combined in a young man; each of these lesions in itself is rare in myeloma. Summary
The case is reported of a young man with extramedullary plasmacytoma presenting with massive cervical lymphadenopathy, pleural effusion and purplish papules on the chest wall. Histopathology of a lymph node from the neck revealed a plasmacytoma. Immunochemical studies on serum and pleural fluid showed M paraprotein of IgG type I.
REFERENCES
CHILDRESS,
W. & ADIE, G. C. (I 959) Plasma cell tumours of mediastinum
surg., ‘9, 794.
CHURG, J. & GORDON, A. poietic system. An. 3. DOLIN, S. & DEWAR, J. P. DURANT, J. R., BARRY, W. Lzncet, EDWARDS,
Path.,
myeloma.
Lesions of the extra-osseous
hema-
20, 934.
(1956) Extramedullary plasmacytoma. Am. 3. Path., 32, 83. E. & LEARNER, N. (1966) The changing face of multiple myeloma.
i, I 19.
G. A report FAVIS, E. A., problem GABRIEL, S. case.
J. (1950) Multiple clin.
and lung. 3. thoruc.
A. & ZAWADSKI, of six cases. Am. KERMAN, H. D. in the diagnosis (1965) Multiple
Db
Chest,
47,
Z. A. (1967) Extraosseous
3.
Med.,
43,
lesions in plasma
cell myeloma.
194.
& SCHILDECKER, W. (1960) Multiple myeloma manifested as a of pulmonary disease. Am. 3. Med., 28, 323. myeloma presenting as pulmonary infiltration. Report of a
123.
I&YES, D. W., BENNETT, W. A. & HECK, F. J. (1952) Extramedullary lesions in multiple myeloma. Review of the literature and pathologic studies. Archs Path., 53, 262. HELL~V~G, C. A. (1943) Extramedullary plasma cell tumours as observed in various locations. Archs
Path.,
36,
95.
HERSKOVICS, T., ANDERSON, H. A. & BAYRD, E. D. Presentation of 2 I cases and review of literature. Dir. INNES, J. & NEWALL, J. (1961) Myelomatosis. Lancet, i, JOHNSON, W. H. jun. & TAYLOR, B. G. (1970) Solitary skin. A review of world literature and report of an NELSON, M. G. & LYONS, A. R. (1957) Plasmacytoma 1275.
(1965) Chest, 239.
Intrathoracic 47,
plasmacytoma.
I.
extramedullary plasmacytoma of the additional case. Cancer, N.Y., 26, 65. of lymph glands. Cancer, .N.Y., JO,
ROWLANDS, B. & SHAW, N. (1954) Extramedullary plasmacytoma. Br. med. J., i, 1302. SIMON, M. A. & EIDLOW, S. (1950) Plasmacytoma of lymphnode. Report of a case with multiple myeloma. .New Engl. 3. Med., 242, 335. SINGH, M. N. (1968) Lymphadenopathy, peripheral neuropathy and bone lesions. Bull. All-India Inst. med. Sci., 2, 166. WILTSHAW, E. (1971) Extramedullary plasmacytoma. Br. med. J., ii, 327.