Intrathoracic Plasmacytomas: Presentation of 21 Cases and Review of Literature

DISEASES of the CHEST Volume 47

JANUARY, 1965

Number

Intrathoracic Plasmacytomas Presentation of 21 Cases and Review of Literature* TEoooRo HERSKOVIc, M.D.,** HowARD

A.

ANDERSEN, M .D., F .c .c.P.t

D. BAYRD, M .D.tt Rochester, Minnesota

AND EDWIN

M

ULTIPLE

MYELOMA

COMMONLY

IS

associated with conditions and symptoms referable to the thorax. Pneumonitis and thoracic pain are not unusual as a result of altered immunologic competence and skeletal defects. Discrete intrathoracic tumors related to myeloma ( plasmacytomas), however, are relatively rare and only 33 cases have been reported in the literature from 1911 through 1960. *From the Mayo Clinic and Mayo Foundation. **Fellow in Medicine. tSection of Medicine. ttSection of Medicine.

FrouRE thorax.

(Case 1) :

This study was undertaken because of difficulty in determining the exact nature of an intrathoracic mass in one of our patients (case 1) who was found to have multiple myeloma. We wondered whether intrathoracic plasmacytomas conformed to a pattern sufficiently to be recognized by their roentgenologic appearance. Consequently, we reviewed the records of 303 patients with multiple myeloma who were seen at the Mayo Clinic during a five-year period. Twenty-one of these patients had intrathoracic plasmacytomas (6.9 per

Posteroanterior (a) and lateral (b) views showing mass anteriorly in right hemiCopyright , 1965, by the American College of Chest Physicians

2

HERSKOVIC, ANDERSEN AND BAYRD

cent), and occasionally the thoracic mass was the first manifestation. ILLUSTRATIVE CASE CASE

1

A 62-year-old woman from Mexico was examined at the Mayo Clinic because of cough and discomfort in her chest for two months. She had noted chills and fever, and a routine roentgenogram had revealed a mass in the right hemithorax. The finding of this mass (Fig. I ) prompted the referral. Hematologic studies revealed 10.0 gm. of hemoglobin per 100 mi., 3,700,000 erythrocytes, and 5200 leukocytes per cubic millimeter with a normal differential count. Examination of a peripheral blood smear revealed marked rouleau formation. The urine was normal except for grade 2 proteinuria. The erythrocyte sedimentation rate was 5 mm. in one hour (Westergren method). Value for plasma proteins was 12.4 gm. per 100 mi. with 8.2 gm. of gamma globulin. Aspiration of bone marrow showed cells typical of multiple myeloma. Because needle aspiration of the intrathoracic mass did not provide a diagnosis, thoracotomy was performed. At operation, the lesion proved to be a plasmacytoma TABLE

Method of Diagnosis Biopsy, bone marrow Biopsy Biopsy Bone marrow

Weakness Chest pain Chest pain Chest pain

Bone marrow Bone marrow Biopsy Bone marrow Biopsy Bone marrow

11 12 13 14 15 16 17

Back pain Mass on routine chest x-ray film Chest pain Chest pain Chest soreness Back pain Chest pain Leg weakness Chest pain

18

Back pain

Bone marrow

19

Chest pain

Biopsy

20 21

Hip pain Upper back pain

Biopsy Biopsy, bone marrow

Case 1 2 3 4 5 6 7 8 9 10

involving the anterior end of the right sixth rib; the lung appeared to be free of disease. REVIEW OF MAYO CLINIC CASES

Symptoms referable to the thorax were the presenting complaints in 1 I of the 21 patients in this series (Table 1). Of the other ten patients, one had an asymptomatic mass on a routine roentgenogram of the thorax, and another had had pneumonitis antedating the diagnosis of myeloma. Pain in the back was noted initially by five patients and was associated with vertebral involvement. In one patient (case 5), whose main complaint was weakness, severe anemia was present, and plasma cells were encountered in the peripheral blood smear. Nineteen of the 21 patients had disseminated plasma cell myeloma at the time the diagnoses were established. Of the remaining two patients, one (case 19) had a plasmacvtoma of one rib and a region of cystic destruction of another; however, other studies including examination of the

)-THORACIC PLASMACYTOMAS:

Initial or Presenting Symptoms or Signs Cough, chest pain Facial swelling Upper back pain Chest pain

Biopsy, bone marrow Bone marrow Biopsy, bone marrow Bone marrow Bone marrow Biopsy Bone marrow

Diseases of the Chost

CASES AT MAYO CLINIC

Location on Thoracic Roentgenogram Mass ( 6 em.), right thorax anteriorly Superior mediastinal mass Intrathoracic mass, destruction of right 5th rib Paravertebral mass, destruction of body of 8th thoracic vertebra Intrathoracic mass, destruction of adjacent ribs Bilateral thoracic masses with rib destruction Mass, left thorax; osteolytic lesions in ribs Large intrathoracic mass, right 6th rib partly destroyed Thoracic mass, destruction of ribs Mass, left thorax ; destruction of 6th rib posteriorly Bilateral intrathoracic masses, destruction of ribs Mass, right thorax; destruction of ribs Normal x-ray appearance, mass on sternum Intrathoracic, extrapulmonary mass Intrathoracic mass, destruction of left 4th rib Mass, left thorax ; destruction of 6th rib Multiple intrathoracic masses, destructive changes in ribs Destruction of 12th thoracic vertebra, paravertebral mass behind cardiac silhouette Expanding lesion of left 6th rib and osteolytic lesion of 2nd rib Intrathoracic mass, destruction of right 5th rib Destruction of 7th thoracic vertebra and left 4th rib, associated soft tissue mass

Volume 47, No. 1 January 196~

INTRATHORACIC PLASMACYTOMAS

~

2 (Case 8): Plasmacytoma of right hemithorax with destruction of right sixth rib posterolaterally. FIGURE

sternal marrow did not reveal disseminated disease. The other patient (case 2) most likely had multiple plasmacytomas, as antemortem and postmortem marrow studies showed no involvement with myeloma. This patient died with mediastinal involvement and respiratory obstruction. The plasmacytomas presumably originated in the ribs in 16 cases, in the vertebrae in three, in the subcutaneous tissue of the thoracic cage in one, and in the mediastinum in one. By roentgenologic study, tumors of the ribs appeared to be soft tissue masses associated with destruction of the involved

3 (Case II): Bilateral thoracic plasmacytomas with destruction of right eighth rib. FIGURE

3

rib; 11 of these tumors were located laterally (Figs. 2, 3 and 4), and the three vertebral tumors appeared as paravertebral masses. Investigation of the pulmonary lesion led to the diagnosis of multiple myeloma in four of these cases. Diagnosis of plasmacytoma was made in 11 cases by means of biopsy of the tumor. Six of these cases also had bone marrow studies, which were positive in four and normal in two ( 2 and 19) . The remaining five had clinical signs and laboratory and roentgenographic findings compatible with diffuse myeloma. In the ten cases in which biopsy was not done, sternal aspiration revealed multiple myeloma, and the nature of the intrathoracic lesion was presumed. REVIEW OF LITERATURE

Although respiratory manifestations, particularly recurrent pneumonia and chest pains, are frequent in myeloma, intrathoracic extension is uncommon. Review of the literature revealed 33 cases of plasmacytomas with such extension (Table 2). The solitary plasmacytoma is histologically identical with multiple myeloma of the bone marrow." Plasmacytoma, however, in bone appears cystic, and larger and more irregular than the smaller, more discrete

4 (Case 21): Plasmacytoma in upper part of left hemithorax with destruction of left fourth rib posteriorly. FIGURE

4

Disuses of the Chest

HERSKOVIC, ANDERSEN AND BAYRD TABLE 2-THORACIC

PLASMACYTOMAS:

22

Author (year) Klose ( 1911 ) 1

23 24 25 26

Divis and Sikl ( 1928) 1 Bross ( 1931 ) 3 Kreibig (1933)• Heindl ( 1933) •

27 28

Ellinger ( 1936) • Janes ( 1939) 7

Tumor Location and Manifestations Chest wall, local invasion Anterior mediastinum Posterior mediastinum Trachea Trachea (2 tumors) bronchus (2 tumors) Trachea (2 tumors) Rib

29

Janes (1939)

Rib

30

Hinz ( 1941 ) 1

Bronchus

31

Jaeger ( 1941) •

32

Gordon and Walker (1944) 10 Aufses ( 1948) 11 Childress and Adie ( 1950) 11 Hayes and associates ( 1952) 15 Merchant ( 1952) ••

Trachea, four local recurrences in 8 years Left lung

Case

33 34 35 36

7

37

Snapper and assoc. (1953) 15

38

Snapper and assoc. (1953) 15

39

Hill and White (1953) 18 Ackerman ( 1953) 11

40

43

Rozsa and Frieman (1953) 11 Rozsa and Frieman (1953) 11 Galgano ( 1955) 11

44

Galgano ( 1955) 11

45

Carson and associates ( 1955 ) 10 Spyker and Kay (1956) 21

41 42

46

Rib Mediastinum, recurrence in 5 years Lung, cecum and bladder Rib Ribs ( 2 tumors), 7 plasmacytomas, no generalized myeloma Mediastinum, lung Left hemithorax Mediastinal lesion, lung involvement Invasion of rib and lung Lung and mediastinal nodes Pleura, ribs and spinal canal Rib Lung Mediastinal node; 12 years later, pulmonary densities Trachea

47

Mathieson ( 1956) 11

48

Grant and Ross (1958) 13 Robson and Knudsen (1959) .. Kennedy and Kneafsey (1959) .. Kennedy and Kneafsey (1959) ..

Trachea (3 tumors), no other involvement Lung, stomach

Kilburn and Schmidt ( 1960) 18 Favis and associates ( 1960) 11 Spear and associates ( 1960) 11

Hilarnode

49 50 51

52 53 54

Bronchus Trachea, recurrence in 4 months

Pleura, lung Rib

CASES

REPORTED IN

LITERATURE

Treatment Resection

Follow-up Postoperative death (cardiac)

Resection Resection

Alive, 3 months Necropsy report Recurrence, 9 months

Resection

Multiple myeloma; death, 2 years Postoperative death (pneumonia)

Resection

Radiotherapy Left upper lobectomy Resection Both lesions resected Both lesions resected Resection, radiotherapy Radiotherapy, I resection, urethane Radiotherapy, I resection, urethane Pneumonectomy, radiotherapy Pneumonectomy, radiotherapy Pneumonectomy,

Multiple plasmacytomas; alive, 25 years Cardiac death, 3 y, years later Pulmonary embolus and death, 5 years later Necropsy report Death I y, years later, no necropsy Alive, 7 years Necropsy report, myeloma present Alive. 8 years Alive, 8 years Multiple myeloma present

radi~therapy

No recurrence, 9 months Pneumonectomy, radiotherapy Pneumonectomy, Death due to cord compression radiotherapy Pneumonectomy, Died 9 months after diagnosis, radiotherapy multiple myeloma present Upper and middle Alive , 2years lobectomies Alive, 2 years Pneumonectomy and resection of mass Pneumonectomy Died from respiratory and resection obstruction of mass Irradiation No progression, 5 years Irradiation to lung Lobectomy

Multiple myeloma, death

Bronchoscopic resection; thoracotomy and resection for recurrence Resection

Alive, I 0 months

Radiotherapy, ethyl urethane Resection

Alive, 2 months

Alive, 2 years

Alive, 2 years

Alive, 7 years

Volume 47, No. 1 January 196~

5

INTRATHORACIC PLASMACYTOMAS

tumor that IS characteristic of multiple myeloma. 1 To ascertain whether plasmacytomas are indeed solitary, examination of bone marrow, electrophoresis of serum proteins, and determination of Bence Jones proteins in the urine should be carried out."0 Bavrd and Heck" and Carson and co-work~rs•• believe that solitary tumors are part of a generalized disease, with these tumors and plasma cell leukemia at opposite ends of the spectrum. Long-term follow-up studies of patients with solitary plasmacytomas have revealed progression to diffuse plasma cell myeloma. 31 However, the prognosis is generally better for the patient with the solitary type. 11' 31 Eight of the 33 patients were regarded as having solitary thoracic plasmacytomas and were alive without evidence of multiple myeloma from nine months to eight years after diagnosis. Seven of these eight patients (cases 39, 42, 45, 50, 51, 52 and 54) were treated surgically, with or without radiotherapy, and one (case 48) received radiotherapy alone to three tracheal plasmacytomas . In the last case, the sizes of the tumors did not increase in three years and no evidence of multiple myeloma was present in five years. In one of Kennedy and Kneafsey's 15 patients (case 51 ) , a tracheal plasmacytoma was originally excised bronchoscopically. However, it recurred four months later and was then removed by open thoracotomy. At the time the eight cases of solitary thoracic plasmacytomas were reported, local recurrence was noted in only one (case 51 ) , and multiple myeloma had not developed in any. Two other patients with apparently solitary plasmacytomas (cases 33 and 34) died from other causes three and one-half and five years, respectively, after the discovery of the plasmacytoma, and there was still no evidence of diffuse mveloma. Two patients (cases 31 and 37) had multiple plasmacytomas; neither had evidence of disseminated myeloma 25 and seven years later, respectively.

In contrast, multiple myeloma in the remaining 21 patients was present at the time of diagnosis of the plasmacytoma or developed soon thereafter. One patient (case 28) died of myeloma two years after resection of an apparently solitary plasmacytoma of a rib. In another (case 41 ) , diffuse myeloma was evident one month after biopsy of a costal plasmacytoma. One patient (case 49), who had irradiation of a plasmacytoma of the right lung, subsequently underwent gastrectomy for a gastric plasmacytoma and died 26 months later with diffuse plasma cell myeloma. Another patient (case 44) also with a costal plasmacytoma and coexistent multiple myeloma, died of pneumonia nine months after the myeloma was diagnosed. Two patients died from complications of their tumors. One (case 43), who had a pleural plasmacytoma with invasion of three ribs and the spinal canal, died from compression of the spinal cord. In the other (case 4 7 ) , a tracheal tumor caused death from respiratory obstruction. Although these lesions may appear solitary at the onset, it is evident that multiple myeloma may be expected to develop; thus, periodic examinations of bone marrow, serum proteins, and urine for Bence Jones proteins are indicated. Those patients with actual solitary lesions were treated successfully by operation and irradiation; in the others, the outlook was that of the systemic disease. SuMMARY

Of 303 patients with multiple myeloma seen at the Mayo Clinic during a five-year period, 21 had intrathoracic plasmacytomas ( 6.9 per cent). Nineteen of the 21 patients had disseminated plasma cell myeloma at the time the diagnosis was established. A definite diagnosis was established by biopsy of the tumor in 11 cases, and a presumptive diagnosis of plasmacytoma was made in ten cases because of the finding of multiple myeloma on sternal marrow aspiration. On roentgenograms of the thorax, 16 of the plasmacytomas appeared ~s soft tissue

6

HERSKOVIC, ANDERSEN AND BAYRD

masses with destruction of the involved rib. Investigation of the pulmonary lesion led to the diagnosis of multiple myeloma in four cases. Reports of 33 cases of solitary intrathoracic plasmacytomas were found in the literature. In eight of these, diffuse plasma cell myeloma still had not been noted nine months to eight years after the diagnosis. Although the prognosis is better for patients with solitary plasmacytomas, periodic study for evidence of dissemination should be undertaken. Treatment, either by surgical removal or by irradiation, should be directed locally to the solitary lesion when it is symptomatic and when diffuse disease cannot be demonstrated. RESUMEN

Entre 303 enfermos de mieloma multiple que se han vista en Ia Clinica Mayo durante 5 anos, 21 tenian plasmocitomas ( 6.9 por ciento). Diecinueve de los 21 tenian mielomas de celulas plasmaticas diseminados al tiempo que el diagn6stico se hizo. Se establecio un diagnostico definido por biopsia del tumor en II de los casas y un diagnostico de presuncion de p 1asmocitoma se hizo en 10 por el hallazgo del mieloma multiple por aspiracion de medula esternal. AI roentgenograma de t6rax, 16 de los plasmocitomas aparecieron como masas de tejido blando con destruccion de Ia costilla afectada. La investigaci6n de Ia lesion pulmonar condujo al diagn6stico de mieloma multiple en cuatro casos. Se han encontrado relatos de 33 casas de plasmocitomas intratoracicos solitarios en Ia literatura medica. En ocho de ellos el mieloma de celdillas plasmaticas difusas no habia sido notado, de nueve meses a ocho anos despues del diagn6stico. Aunque el pron6stico es mejor para los enfermos con plasmocitomas solitaries, el estudio peri6dico para descubrir Ia diseminacion debe emprenderse. El tratamiento, ya sea quirurgico para extirpaci6n 0 radiacion, debe enfocarse directamente y localmente a Ia lesion solitaria cuando es sintomatica y cuando Ia enfermedad difusa no puede demostrarse. RESUME

Sur 303 malades atteints de myelomes multiples, observes a Ia Clinique Mayo pendant une periode de cinq ans, 21 etaient atteints de plasmacytomes intrathoraciques ( 6,9%). 19 mala des sur les 21 avaient des cellules de myelomes disseminees dans le plasma au moment ou le diagnostic fut etahli. Un diagnostic definitif fut etahli par Ia biopsie de Ia tumeur dans II cas, et un

Diseases of the Chest

diagnostic presomptif de plasmacytome fut fait dans dix cas, par Ia constatation de myelomes par examen de Ia moelle osseuse par ponction sternale. Sur les radiographies du thorax, 16 des plasmacytomes apparurent comme des masses de tissu peu dense, avec destruction de Ia cote atteinte. L'examen de Ia lesion pulmonaire conduisit au diagnostic de myelome multiple dans quatre cas. L'auteur a trouve dans Ia litterature 33 communications de plasmacytome intrathoracique isole. Sur huit d'entre eux, des cellules de myelome disseminees dans le plasma n'avaient pas encore ete notes de neuf mois a huit ans apres le diagnostic. Bien que le pronostic soit meilleur pour les malades atteints de plasmacytomes solitaires, on devrait entreprendre des recherches periodiques pour mettre en evidence Ia dissemination. Le traitement, soit par exerese chirurgicale, soit par irradiation, devrait etre dirige localement sur Ia lesion solitaire lorsqu'on a pu Ia mettre en evidence et lorsque Ia maladie diffuse ne peut etre prouvee. ZusAMMENFASSUNG

Von 303 Patienten mit multiplen Myelomen, die sich an der Mayo-Klinik wahrend einer Fiinfjahresperiode vorstellten, hatten 21 intrathorakale Plasmocytome ( 6,9%). 19 der 21 Patienten hatten disseminierte Plasmazellmyelome zu dem Zeitpunkt, an dem die Diagnose gestellt wurde. Definitive Tumordiagnose wurde in II Fallen durch Biopsie gestellt, und in 10 Fallen wurde eine vorlaufige Diagnose eines Plasmocytoms gestellt aufgrund der Befunde von multiplen Myelomen bei der Stemumknochenmarkspunktion. Bei Rontgenuntrsuchungen des Thorax erschienen 16 der Plasmocytome als wolkig-weiche Gewebsmassen mit Destruktion der befallenen Rippen. Eine Untersuchung der Lungenherde fiihrte zur Diagnose multipler Myelome in 4 Fallen. Berichte in der Literatur iiber solitare intrathorakale Plasmocytome wurden in 33 Fallen gefunden. In 8 von ihnen wurden die diffusen Plasmozellmyelome nach der Diagnose nicht bemerkt in einem Zeitraum, der Zwischen 9 Monaten his 8 Jahren schwankte. Obwohl die Prognose fiir Patienten mit solitaren Plasmocytomen giinstiger ist, sollte man periodisch untersuchen auf das Vorliegen einer Disseminiation. Die Behandlung, sei sie chirurgisch oder strahlentherapeutisch, mu(3 direkt i:irtlich auf die solitaren Herrle gerichtet sein, sofern sich Symptome ergeben und eine diffuse Ausbreitung nicht nachweisen ist. Complete reference list will appear in reprints.

For reprints. please write Section of Publications, Mayo Clinic, Rochester, Minnesota.