??Brief Communication
EXTRAMEDULLARY PASMACYTOMA OF THE UPPER RESPIRATORY PASSAGESt ZBIGNIEW PETROVICH, M.D.,S BEN FISHKIN, M.D.& ROBERT E. HITTLE, M.D.,7 MARIO ACQUARELLI, M.D.” and RICHARD BARTON, M.D.tt Radiation
Therapy
Service. VA Wadsworth
Hospital Center. Los Angeles, CA 90073, U.S.A.
This paper is a review of the clinical experience with plasmacytoma of the upper respiratory passages seen in the Department of Radiotherapy at our institution from 1947 to 1976. Seven patients are discussed. A tumor mass was present at diagnosis in all patients. 2/7 presented with cervical lymph adenopathy. l/7 had cervical lymph adenopathy 4 years after diagnosis, coincidental with wide spread metastases. All patients were treated primarily with radiation following biopsy and histologic diagnosis. Two patients had partial excisions, and two patients received chemotherapy. Follow-up extends from 4 to 23 years. 6/7 were free of disease at last evaluation, and l/7 died of disseminated disease 9 years after initial treatment. Extramedullary
plasmacytoma,
Radiotherapy.
INTRODUCTION
and/or Bence Jones Protein (BJP) are demonstrable in serum and/or urine in 99% of patients with classical multiple myeloma.” (a) Plasma cell leukemia-as above with 7500 plasma cells per mm3 in peripheral blood.”
Extramedullary plasmacytoma is a rare primary malignant plasma cell tumor first described by Schridde in 1905.16 Although these tumors are known to’originate in a variety of anatomic sites,2,5,‘2 the majority of them occur in the upper respiratory passages.‘.“‘.” Helwig,“’ Dolin and Dewar,S and Castro et ~1.~ provided successive literature reviews. Castro et al. found 192 cases of head and neck primary extramedullary plasmacytomas which were distributed as follows: nose and paranasal sinuses, 72; nasopharynx, 41; tonsil pharynx, 26; other upper respiratory and digestive tract sites, 53. The malignant plasma cell neoplasms can be classified as follows:”
2. Solitary plasmacytoma of bone A localized lesion at time of detection. globulins in serum and/or urine (BJP) may be present. Dissemination to myeloma virtually always occurs.
Monoclonal occasionally plasma cell
3. Extramedullary plasmacytomas A primary soft tissue neoplasm with a 75% incidence in the upper respiratory and digestive tract. Single or multiple tumors may be present, monoclonal globulin in serum and/or urine (BJP) are seen occasionally.’ This paper reviews our clinical experiments with extramedullary plasmacytoma of the upper respiratory passages. All patients were treated and followed in
1. Plasma cell myeloma (multiple myeloma) The red bone marrow is defusely involved; multiple osteolytic lesions and profound osteoporosis produce classical radiographic findings; monoclonal proteins
(Radiation Therapist, Associate Professor of Radiology, University of Southern California. “Chief, Head and Neck Section; Professor of Surgery, UCLA. ttConsultant in Head and Neck Surgery, Goldwyn Research Fellow in Oncology, UCLA Cancer Center. Reprint requests to: Z. Petrovich, M.D., Chief, Radiation Therapy Service, Los Angeles, CA 90073, U.S.A.
tPresented at the 18th Annual Meeting of the American Society of Therapeutic Radiologists, 12-16 Oct. 1976, Atlanta, Georgia. SChief, Radiation Therapy Service, VA Wadsworth Hospital Center. Los Angeles, California; Adjunct Assistant Professor of Radiology. UCLA. OChief, Laboratory Service, VA Wadsworth Hospital Center, Los Angeles, California; Professor of Pathology, UCLA. 133
Radiation Oncology 0 Biology 0 Physics
124
July-August
the Department of Radiotherapy from April 1974 to October 1976. Some information on 6 of these patients had been presented previously,‘,* but additional data are available on several of them.
METHODS
6oCo radiation. Two patients had partial excision of their tumor, and 2 patients who had skeletal metastases received chemotherapy. The radiation dose schedules and delivery techniques varied during the 28 year period, and are found in the following case reports. A summary of the treatment results is found in Table 1.
AND MATERIALS
Seven patients with confirmed histologic diagnoses of extramedullary plasmacytomas of the upper respiratory tract are reviewed. Clinical, laboratory and radiographic information was acquired from hospital records and patient radiographic files. A case report on each patient will be presented.
CASE
to Wadsworth Hospital in April 1947, with a diagnosis of plasmacytoma of the right maxillary antrum. Several weeks prior to admission, the patient had a right upper molar extracted and tumor was observed in the tooth socket. Histological diagnosis of a biopsy performed at a tumor clinic was plasmacytoma. The patient was referred to the hospital for further workup and treatment. On admission he gave a two year history of right nasal obstruction. Examination revealed swelling of the right side of the face. A lobulated reddish-gray tumor mass was noted filling the right nasal cavity and protruding from the tooth socket. No lymph nodes were palpable in the neck and no other physical findings were present. Radiographs demonstrated opacification of the right nasal cavity and right maxillary antrum with bone destruction of the superior and lateral walls of
All patients were males whose ages ranged from 34 to 74 years. Symptoms existed from a few weeks to 2 years. Mild to severe nasal obstruction was present in 4 of 7 patients. Epitaxis was present in 1 patient, hoarseness in another, and 1 patient was asymptomatic. A definable tumor mass was present at the time of diagnosis in all patients. The primary sites were: nasopharynx, 5; maxillary antrum, 1; and epiglottis, 1. Metastases to cervical lymph nodes were present in 2 patients at the time of diagnosis, and in 1 patient simultaneously with the appearence of disseminated disease. All patients were treated with radiation. Five of 7 patients with orthovoltage radiation, and 2 with
P&lent Number
Primary
stte
Max1 I lary
1. A summary
Age
REPORTS
Patient 1 A 34 year old male was admitted
RESULTS
Table
1977, Volume 2. No. 7 and No. 8
of the treatment
CWViCel Lymph Nodes
results
knerallred DlSeeSe‘
Results
Therapy
I
Antrum
34
0
0
Radlatlon
23 years
N.E.D.'
2
Nasopharynx
50
0
0
Radlatlon
13 years
N.E.D*
3
Nasopharynx
68
0
0
Partial exclslon,
I3 years
N.E.D.*
Radlatlon
L.F.U.""
4
Nasopharynx
63 0
5
Nasopharynx
68
0
+
+
PartI. eXClSlOn,
I3 years
Radlatlon
L.F.U."'
Radlatlon
9 years dead controlled
Chemotherapy
N.E.D.
disease
6
Epiglottis
7
Nasopharynx
74
57
+
0
+
+
Radlatlon
I Chemotherapy
6 years
I4
years
Radlatlon
*No
evidence
of
disease
**Lost
to
follow-up
+ Yes
0 No
N.E.D.*
N.E.D.*
Extramedullary
pasmacytoma
of the upper respiratory
the antrum. Radiotherapy was given with 200 kVp,t 20 mA,t 1.8 mm CuHVL,t 50 cm TSD.t Four portals were used to deliver 4700 rad tumor dose in 29 fractions over 30 days to the right antrum and nasal cavity. An additional 2500 rad tumor dose in 10 fractions over 14 days was given to the right neck. A good response was observed. Seven months later a recurrence of the tumor in the right antrum was treated with 2760 rad in 21 fractions over 30 days, using the same quality of radiation. The tumor regressed completely. Four months later the tumor recurred again in the same area, a dose of 2260 rad was given in 20 fractions over 31 days. Complete regression of the tumor occurred. A biopsy of the antrum in May 1951, showed no evidence of tumor. The patient was free of tumor at last follow-up at 23 years. Patient 2 A 58 year old man was admitted to the hospital in February 1952, with a short history of a bloody nasal discharge. Examination revealed a 2.5 x 2 cm mass in the right posterior nasopharynx. No palpable lymph nodes were present in the neck. Biopsy demonstrated plasmacytoma. Radiotherapy was given with 200 kVp, 20 mA, 1.5 mm Cu HVL, 50 cm TSD. Six portals were used to deliver 6750 rad in 26 fractions over 35 days to the nasopharynx. Complete resolution of the tumor mass occurred. Sixteen months later a recurrence in the nasopharynx was confirmed by biopsy. The tumor disappeared after 3369rad was administered in 20 treatments over 26 days. The patient was free of tumor when he died 13 years later of intercurrent disease. Patient 3 A 68 year old male had a routine physical examination performed in June 1953. A 2 x 1 cm reddish-gray polypoid mass was found in the right nasopharynx. The remainder of the examination was unremarkable. Histological examination of an excisional biopsy was plasmacytoma. Radiotherapy was given with 200 kVp, 15 mA, 1.5 mm Cu HVL, 50 cm TSD. Three portals were used to deliver 5283 rad tumor dose to the nasopharynx in 22 treatments over 29 days. The patient remained free of tumor during the following 13 years, and was lost to follow-up in 1966. Patient 4 A 63 year old male was admitted to the hospital in April 1956, with a 3 week history of left nasal obstruction. Physical examination showed a 1.5 x 1.5 cm mass in the nasopharynx. No other relevant physical tKilovolts
peak;
Milliamperes;
Half value
layer;
Target
passages 0 Z.
PETROVICH et al.
725
findings were present. The mass was removed by snare and histological examination showed plasmacytoma. Radiotherapy was given with 200 kVp, 15 mA, 1.7 mm Cu HVL, 50 TSD. Five portals were used to deliver 6240rad tumor dose in 22 treatments over 30 days to the nasopharynx. The patient remained clinically free of tumor, and was lost to follow-up at 13 years. Patient 5 A 68 year old male was admitted to the hospital in May 1958, because of a progressive increase in left nasal obstruction of 7 months duration. A nasal biopsy performed at an outside hospital established a diagnosis of plasmacytoma. Physical examination revealed a pale pink tumor mass that completely obstructed the left nasal cavity, and extended back to obliterate the nasopharynx and hang free below the soft palate. No other relevant physical findings were noted. Radiographs demonstrated complete opacification of the left nasal cavity, left maxillary antrum and the nasopharynx. Radiotherapy was given to the nasopharynx, antrum and nasal cavity with 250 kVp, 15 mA, 2.3 mm Cu HVL, 50 TSD. Seven portals were used to deliver 6168 rad tumor dose in 18 treatments over 25 days. Residual tumor in the nasopharynx was still evident at the end of treatment. An additional 2160 rad tumor dose was administered in 27 treatments over 38 days. Eight weeks post therapy, the tumor had completely regressed. In June 1962, an ulcerated mass was observed in the right thigh. Subsequently multiple metastases to skin, the peripheral skeleton and lymph nodes required multiple courses of chemotherapy and radiotherapy. The patient died of his disease in 1967-nine years after diagnosis. Despite the extensive metastases, the primary site was ultimately controlled. Patient 6 A 74 year old man was admitted to the hospital in October 1970, because of slowly enlarging mass on the right side of the neck. Two years previously, a right cervical plasmacytoma had been removed at another hospital. Physical examination on admission revealed a firm lobulated right neck mass that measured 13 x 8 x 4 cm. A 2 x 3 cm dark reddish smooth pedunculated tumor was found involving the right side of the laryngeal surface of the epiglottis. The right false cord was edematous. The remainder of the examination was within normal limits. Radiographs demonstrated a large right neck mass with well defined epiglottic mass. Enlargement of the skin distance.
726
Radiation Oncology 0 Biology 0 Physics
right false cord with obliteration of the right ventricle was also noted. Histologic examination of the epiglottic tumor showed plasmacytoma. 6oCo irradiation (7312 rad tumor dose in 35 treatments over 61 days) was given to the neck and epiglottic tumor. The tumor resolved with therapy. A biopsy of the epiglottis performed 2 years later showed no evidence of tumor. The patient was clinically free of tumor 6 years post radiotherapy. Patient 7 A 50 year old man was referred to this Radiotherapy Department in October 1973, for the treatment of his plasmacytoma. The patient was admitted to an outside hospital in December 1971, because of progressive hearing loss for 3 weeks. Examination showed a large nasopharyngeal mass and right cervical nodes. A nasopharyngeal biopsy showed plasmacytoma, and a bone marrow aspirate was consistent with multiple myeloma. In March 1972, the patient was admitted to the Sepulveda VA Hospital where studies showed in addition to the nasopharyngeal mass, bilateral cervical lymph adenopathy, an abnormal serum protein electrophoresis and immunoelectrophoresis, and tumor cells in the bone marrow. The diagnosis was
July-August
1977, Volume 2, No. 7 and No. 8
extramedullary plasmacytoma with dissemination. The patient was treated with monthly cycles of Melphalan and Prednisone with good response. In March 1973, serum protein and bone marrrow studies were normal. No significant change in the nasopharyngeal mass had occurred. From April to September 1973, the patient was lost to follow-up only to return because of nasal obstruction, redness and swelling of the right face and rapidly enlarging cervical lymph nodes. Examination in this Radiotherapy Department revealed swelling and redness of the right face, a right exophthalmos, bilateral cervical lymph nodes measuring up to 7 cm in diameter, and a nasopharyngeal mass that filled the nasopharynx. Laboratory studies showed elevated serum proteins. A bone marrow aspiration was normal. Radiographs demonstrated additionally, opacification of the right antrum with destruction of the anterior and lateral walls (Figs. 1 and 2) and an osteolytic lesion in the body of sixth cervical vertebra. 6oCo therapy (6700 rad tumor dose in 33 treatments over 50 days) was delivered to the nasopharynx, anterior ethmoids and right antrum. Simultaneous therapy was administered to the neck and C-6 vertebra-left neck (6000rad in 30 treatments over 42 days) right neck (5000rad in 42 days) and C-6
Fig. 1. A large mass filling completely the nasopharynx.
Extramedullary
pasmacytoma
Fig. 2. Opacification
of the upper respiratory
passages 0 Z. PETROVKH
of the right antrum with bone destruction
(5500rad in 42 days). All tumor regressed completely (Figs. 3 and 4). Melphalan and Prednisone therapy was instituted in December 1973, and completed in October 1974. The patient was clinically free of tumor more than 4 years after initiation of therapy. DISCUSSION Seven cases of plasmacytoma arising in the upper respiratory and digestive tracts have been presented. The presenting characteristics of this group of patients fits the existing data published in the literature.3.‘5X’8 The duration of symptoms (1 month to 2 years), age at diagnosis (34 years to 74 years with a median of 59 years) pattern of presenting symptoms
et al.
727
of the lateral wall.
(nasal obstruction 4, bleeding 1, hoarseness 1) and prognosis are similar to the data reported by others. Dissemination occurs in one-third, lymph node metastases are present in one-third and more than one-half of patients survive 5 years or longer.‘.“.” The observed patterns of tumor extension and metastases closely correlates with those of other tumors arising in the upper respiratory and digestive tracts. The radiotherapy treatment techniques utilized in this group of patients closely resembles that used for other tumor types, and with similar results. A tumor dose of 6000-8000rad was required to achieve local control. Patients who recurred locally or who had persistent disease at the end of radio-
728
Radiation Oncology 0 Biology 0 Physics
July-August
1977, Volume 2, No. 7 and No. 8
Fig. 3. Lateral view of nasopharynx. Upper view obtained during the radiotherapy in November 1973, shows partial resolution of the large nasopharyngeal mass. Lower view obtained in January 1976, shows complete resolution of tumor mass. therapy were given additional treatment. Although the reason is not clear for the success achieved with suppliment doses of 2200-3400rad for persistent or recurrent disease, it is postulated that this observed phenomenon is probably a tumor bed effect. It is a common experience to radiotherapists that such doses given as preliminary treatment are virtually ineffectual in controlling this tumor; yet for supplemental treatment of persistence and recurrence these modest doses have been sufficient to control the tumor in previously irradiated sites. It is apparent in these 7 patients that the use of
radiotherapy as primary treatment has achieved excellent control of tumor with preservation of the function and appearance of the patient. We feel, therefore, that although surgery has achieved similar tumor control and survival, radiotherapy is preferable as the primary modality of treatment in patients with localized extramedullary plasmacytoma.6~g~‘9~20 Alexanian et al. have demonstrated the usefulness of chemotherapy in treatment of multiple myeloma in some patients.’ We have substantiated this in patient 7 who achieved a long term tumor free interval when his systemic disease was treated with Melphalan and
Extramedullary
Fig. 4. Views of maxillary
pasmacytoma
antrum.
of the upper respiratory
SUMMARY patients arising in the
toma ported. (2) Either management
primary provides
with extramedullary plasmacyupper respiratory tract are resurgical equivalent
PETROVICH et al.
Two studies of the antrum reveal no evidence restoration of the antral wall.
Prednisone. Patient 5 survived nearly 5 years after dissemination with combined chemotherapy-radiotherapy treatment. It is our opinion that patients with and those with dissemination nodal metastases, should have treatment which includes chemotherapy.
(1) Seven
passages 0 Z.
or radiotherapy control of disease.
729
of tumor mass and
(3) Radiotherapy provides superior functional and cosmetic end results. (4) Metastasis to regional lymph nodes increase the risk of dissemination. (5) Frequent long term survival in this group of patients warrants appropriate and intensive therapy. (6) Chemotherapy is of value when dissemination is present. We feel that radiotherapy is the modality of choice for tumor control, preservation of function and cosmetic end result in the management of extramedullary plasmacytomas of the upper respiratory passages.
REFERENCES 1. Alexanian,
2. 3. 4.
5.
R., Bonnet, J., Gehan, E., Haut, A., Hewlett, J., Lane, M., Monto, R., Wilson, H.: Combined chemotherapy for multiple myeloma. Cancer 30: 382-389, 1972. Anderson, P.R.: Extramedullary plasmacytomas. Acta Radiol. 32: 363-374, 1949. Carson, C.P., Ackerman, L.V., Maltby, J.D.: Plasma cell myeloma. Am. J. Clin. Path. 25: 849-888, 1955. Castro, E.B., Lewis, J.S., Strong, E.W.: Plasmacytoma of paranasal sinuses and nasal cavity. Arch. Otofaryngal. 97: 326-329, 1973. Dolin, S., Dewar, J.P.: Extramedullary plasmacytoma. Am. .l. Pathol. 32: 83-103, 1956.
6. Ewing, M.R., Foote, Jr., F.W.: Plasma cell tumors of the mouth and upper air passages. Cancer 5: 499-513, 1952. 7. Fishkin, B.G., Spiegelberg, H.L.: Cervical lymph node metastasis as the first manifestation of localized extramedullary plasmacytoma: Cancer 58: 1641-1644, 1976. 8. Fishkin, B.G., Spiegelberg, H.L.: Extramedullary (soft tissue) plasmacytoma (Abstract). Am. J. Clin. Path. 59: 150, 1973. 9. Gromer, R.C., Duvall, A.J.: Plasmacytoma of the head and neck. J. Laryngol. Otol. 87: 861-872, 1973. 10. Hellwig, C.A.: Extramedullary plasma cell tumors as
730
11. 12. 13.
14.
15.
Radiation
Oncology
0
Biology
0
Physics
observed in various locations. Arch. Path. 36: 95-111, 1943. Helmus, C.: Extramedullary plasmacytomas. Laryngoscope 74: 553-358, 1%4. Kutcher, R., Ghatak, N.R., Leeds, N.E.: Piasmacytoma of the calvaria. Radiology 113: 111-115, 1974. Osserman, E.F., Farhangi, M.: Plasma cell myeloma. In Hematology, ed. by Williams, W.J., Beutler, E., Ersler, A.J., Roudles, R.W. New York, McGraw-Hill, 1972, pp. 960-962. Poole, A.G., Marchetta, F.C.: Extramedullary plasmacytoma of the head and neck. Cancer 22: 14-21, 1968. Rawson, A.J., Eyler, P.W., Horn, Jr., R.C.: Plasma cell tumors of the respiratory tract. Am. J. Path. 25: 445461, 1950.
July-August
1977, Volume
2, No.
7 and No.
8
16. Schridde, H.: Weitere Untersuchungen Uber Die Kornelungen Der Plasmazellen Zentrabl. E Allg. Path. Path. Anat. 16: 433435, 1905. 17. Stone, H.B., Cole, T.B.: Extramedullary plasmacytomas of head and neck. South. Med. J. 64: 1386-1388, 1971. 18. Stout, A.P., Kenney, F.R.: Primary plasma cell tumors of the upper air passages and oral cavity. Cancer 2: 261-277, 1949. 19. Todd, I.D.H.: Treatment of solitary plasmacytoma. Clin. Radiol. 16: 395-399, 1%5. 20. Webb. H.E., Harrison, E.G., Masson, J.K., Remine, W.H.: Extramedullary myeloma (Plasmacytoma) of the respiratory tract and oropharynx. Cancer 15: 11421155. 1%2.
EXTRAMEDULLARY PASMACYTOMA OF THE UPPER RESPIRATORY PASSAGESt ZBIGNIEW PETROVICH, M.D.,S BEN FISHKIN, M.D.& ROBERT E. HITTLE, M.D.,7 MARIO ACQUARELLI, M.D.” and RICHARD BARTON, M.D.tt Radiation
Therapy
Service. VA Wadsworth
Hospital Center. Los Angeles, CA 90073, U.S.A.
This paper is a review of the clinical experience with plasmacytoma of the upper respiratory passages seen in the Department of Radiotherapy at our institution from 1947 to 1976. Seven patients are discussed. A tumor mass was present at diagnosis in all patients. 2/7 presented with cervical lymph adenopathy. l/7 had cervical lymph adenopathy 4 years after diagnosis, coincidental with wide spread metastases. All patients were treated primarily with radiation following biopsy and histologic diagnosis. Two patients had partial excisions, and two patients received chemotherapy. Follow-up extends from 4 to 23 years. 6/7 were free of disease at last evaluation, and l/7 died of disseminated disease 9 years after initial treatment. Extramedullary
plasmacytoma,
Radiotherapy.
INTRODUCTION
and/or Bence Jones Protein (BJP) are demonstrable in serum and/or urine in 99% of patients with classical multiple myeloma.” (a) Plasma cell leukemia-as above with 7500 plasma cells per mm3 in peripheral blood.”
Extramedullary plasmacytoma is a rare primary malignant plasma cell tumor first described by Schridde in 1905.16 Although these tumors are known to’originate in a variety of anatomic sites,2,5,‘2 the majority of them occur in the upper respiratory passages.‘.“‘.” Helwig,“’ Dolin and Dewar,S and Castro et ~1.~ provided successive literature reviews. Castro et al. found 192 cases of head and neck primary extramedullary plasmacytomas which were distributed as follows: nose and paranasal sinuses, 72; nasopharynx, 41; tonsil pharynx, 26; other upper respiratory and digestive tract sites, 53. The malignant plasma cell neoplasms can be classified as follows:”
2. Solitary plasmacytoma of bone A localized lesion at time of detection. globulins in serum and/or urine (BJP) may be present. Dissemination to myeloma virtually always occurs.
Monoclonal occasionally plasma cell
3. Extramedullary plasmacytomas A primary soft tissue neoplasm with a 75% incidence in the upper respiratory and digestive tract. Single or multiple tumors may be present, monoclonal globulin in serum and/or urine (BJP) are seen occasionally.’ This paper reviews our clinical experiments with extramedullary plasmacytoma of the upper respiratory passages. All patients were treated and followed in
1. Plasma cell myeloma (multiple myeloma) The red bone marrow is defusely involved; multiple osteolytic lesions and profound osteoporosis produce classical radiographic findings; monoclonal proteins
(Radiation Therapist, Associate Professor of Radiology, University of Southern California. “Chief, Head and Neck Section; Professor of Surgery, UCLA. ttConsultant in Head and Neck Surgery, Goldwyn Research Fellow in Oncology, UCLA Cancer Center. Reprint requests to: Z. Petrovich, M.D., Chief, Radiation Therapy Service, Los Angeles, CA 90073, U.S.A.
tPresented at the 18th Annual Meeting of the American Society of Therapeutic Radiologists, 12-16 Oct. 1976, Atlanta, Georgia. SChief, Radiation Therapy Service, VA Wadsworth Hospital Center. Los Angeles, California; Adjunct Assistant Professor of Radiology. UCLA. OChief, Laboratory Service, VA Wadsworth Hospital Center, Los Angeles, California; Professor of Pathology, UCLA. 133
Radiation Oncology 0 Biology 0 Physics
124
July-August
the Department of Radiotherapy from April 1974 to October 1976. Some information on 6 of these patients had been presented previously,‘,* but additional data are available on several of them.
METHODS
6oCo radiation. Two patients had partial excision of their tumor, and 2 patients who had skeletal metastases received chemotherapy. The radiation dose schedules and delivery techniques varied during the 28 year period, and are found in the following case reports. A summary of the treatment results is found in Table 1.
AND MATERIALS
Seven patients with confirmed histologic diagnoses of extramedullary plasmacytomas of the upper respiratory tract are reviewed. Clinical, laboratory and radiographic information was acquired from hospital records and patient radiographic files. A case report on each patient will be presented.
CASE
to Wadsworth Hospital in April 1947, with a diagnosis of plasmacytoma of the right maxillary antrum. Several weeks prior to admission, the patient had a right upper molar extracted and tumor was observed in the tooth socket. Histological diagnosis of a biopsy performed at a tumor clinic was plasmacytoma. The patient was referred to the hospital for further workup and treatment. On admission he gave a two year history of right nasal obstruction. Examination revealed swelling of the right side of the face. A lobulated reddish-gray tumor mass was noted filling the right nasal cavity and protruding from the tooth socket. No lymph nodes were palpable in the neck and no other physical findings were present. Radiographs demonstrated opacification of the right nasal cavity and right maxillary antrum with bone destruction of the superior and lateral walls of
All patients were males whose ages ranged from 34 to 74 years. Symptoms existed from a few weeks to 2 years. Mild to severe nasal obstruction was present in 4 of 7 patients. Epitaxis was present in 1 patient, hoarseness in another, and 1 patient was asymptomatic. A definable tumor mass was present at the time of diagnosis in all patients. The primary sites were: nasopharynx, 5; maxillary antrum, 1; and epiglottis, 1. Metastases to cervical lymph nodes were present in 2 patients at the time of diagnosis, and in 1 patient simultaneously with the appearence of disseminated disease. All patients were treated with radiation. Five of 7 patients with orthovoltage radiation, and 2 with
P&lent Number
Primary
stte
Max1 I lary
1. A summary
Age
REPORTS
Patient 1 A 34 year old male was admitted
RESULTS
Table
1977, Volume 2. No. 7 and No. 8
of the treatment
CWViCel Lymph Nodes
results
knerallred DlSeeSe‘
Results
Therapy
I
Antrum
34
0
0
Radlatlon
23 years
N.E.D.'
2
Nasopharynx
50
0
0
Radlatlon
13 years
N.E.D*
3
Nasopharynx
68
0
0
Partial exclslon,
I3 years
N.E.D.*
Radlatlon
L.F.U.""
4
Nasopharynx
63 0
5
Nasopharynx
68
0
+
+
PartI. eXClSlOn,
I3 years
Radlatlon
L.F.U."'
Radlatlon
9 years dead controlled
Chemotherapy
N.E.D.
disease
6
Epiglottis
7
Nasopharynx
74
57
+
0
+
+
Radlatlon
I Chemotherapy
6 years
I4
years
Radlatlon
*No
evidence
of
disease
**Lost
to
follow-up
+ Yes
0 No
N.E.D.*
N.E.D.*
Extramedullary
pasmacytoma
of the upper respiratory
the antrum. Radiotherapy was given with 200 kVp,t 20 mA,t 1.8 mm CuHVL,t 50 cm TSD.t Four portals were used to deliver 4700 rad tumor dose in 29 fractions over 30 days to the right antrum and nasal cavity. An additional 2500 rad tumor dose in 10 fractions over 14 days was given to the right neck. A good response was observed. Seven months later a recurrence of the tumor in the right antrum was treated with 2760 rad in 21 fractions over 30 days, using the same quality of radiation. The tumor regressed completely. Four months later the tumor recurred again in the same area, a dose of 2260 rad was given in 20 fractions over 31 days. Complete regression of the tumor occurred. A biopsy of the antrum in May 1951, showed no evidence of tumor. The patient was free of tumor at last follow-up at 23 years. Patient 2 A 58 year old man was admitted to the hospital in February 1952, with a short history of a bloody nasal discharge. Examination revealed a 2.5 x 2 cm mass in the right posterior nasopharynx. No palpable lymph nodes were present in the neck. Biopsy demonstrated plasmacytoma. Radiotherapy was given with 200 kVp, 20 mA, 1.5 mm Cu HVL, 50 cm TSD. Six portals were used to deliver 6750 rad in 26 fractions over 35 days to the nasopharynx. Complete resolution of the tumor mass occurred. Sixteen months later a recurrence in the nasopharynx was confirmed by biopsy. The tumor disappeared after 3369rad was administered in 20 treatments over 26 days. The patient was free of tumor when he died 13 years later of intercurrent disease. Patient 3 A 68 year old male had a routine physical examination performed in June 1953. A 2 x 1 cm reddish-gray polypoid mass was found in the right nasopharynx. The remainder of the examination was unremarkable. Histological examination of an excisional biopsy was plasmacytoma. Radiotherapy was given with 200 kVp, 15 mA, 1.5 mm Cu HVL, 50 cm TSD. Three portals were used to deliver 5283 rad tumor dose to the nasopharynx in 22 treatments over 29 days. The patient remained free of tumor during the following 13 years, and was lost to follow-up in 1966. Patient 4 A 63 year old male was admitted to the hospital in April 1956, with a 3 week history of left nasal obstruction. Physical examination showed a 1.5 x 1.5 cm mass in the nasopharynx. No other relevant physical tKilovolts
peak;
Milliamperes;
Half value
layer;
Target
passages 0 Z.
PETROVICH et al.
725
findings were present. The mass was removed by snare and histological examination showed plasmacytoma. Radiotherapy was given with 200 kVp, 15 mA, 1.7 mm Cu HVL, 50 TSD. Five portals were used to deliver 6240rad tumor dose in 22 treatments over 30 days to the nasopharynx. The patient remained clinically free of tumor, and was lost to follow-up at 13 years. Patient 5 A 68 year old male was admitted to the hospital in May 1958, because of a progressive increase in left nasal obstruction of 7 months duration. A nasal biopsy performed at an outside hospital established a diagnosis of plasmacytoma. Physical examination revealed a pale pink tumor mass that completely obstructed the left nasal cavity, and extended back to obliterate the nasopharynx and hang free below the soft palate. No other relevant physical findings were noted. Radiographs demonstrated complete opacification of the left nasal cavity, left maxillary antrum and the nasopharynx. Radiotherapy was given to the nasopharynx, antrum and nasal cavity with 250 kVp, 15 mA, 2.3 mm Cu HVL, 50 TSD. Seven portals were used to deliver 6168 rad tumor dose in 18 treatments over 25 days. Residual tumor in the nasopharynx was still evident at the end of treatment. An additional 2160 rad tumor dose was administered in 27 treatments over 38 days. Eight weeks post therapy, the tumor had completely regressed. In June 1962, an ulcerated mass was observed in the right thigh. Subsequently multiple metastases to skin, the peripheral skeleton and lymph nodes required multiple courses of chemotherapy and radiotherapy. The patient died of his disease in 1967-nine years after diagnosis. Despite the extensive metastases, the primary site was ultimately controlled. Patient 6 A 74 year old man was admitted to the hospital in October 1970, because of slowly enlarging mass on the right side of the neck. Two years previously, a right cervical plasmacytoma had been removed at another hospital. Physical examination on admission revealed a firm lobulated right neck mass that measured 13 x 8 x 4 cm. A 2 x 3 cm dark reddish smooth pedunculated tumor was found involving the right side of the laryngeal surface of the epiglottis. The right false cord was edematous. The remainder of the examination was within normal limits. Radiographs demonstrated a large right neck mass with well defined epiglottic mass. Enlargement of the skin distance.
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right false cord with obliteration of the right ventricle was also noted. Histologic examination of the epiglottic tumor showed plasmacytoma. 6oCo irradiation (7312 rad tumor dose in 35 treatments over 61 days) was given to the neck and epiglottic tumor. The tumor resolved with therapy. A biopsy of the epiglottis performed 2 years later showed no evidence of tumor. The patient was clinically free of tumor 6 years post radiotherapy. Patient 7 A 50 year old man was referred to this Radiotherapy Department in October 1973, for the treatment of his plasmacytoma. The patient was admitted to an outside hospital in December 1971, because of progressive hearing loss for 3 weeks. Examination showed a large nasopharyngeal mass and right cervical nodes. A nasopharyngeal biopsy showed plasmacytoma, and a bone marrow aspirate was consistent with multiple myeloma. In March 1972, the patient was admitted to the Sepulveda VA Hospital where studies showed in addition to the nasopharyngeal mass, bilateral cervical lymph adenopathy, an abnormal serum protein electrophoresis and immunoelectrophoresis, and tumor cells in the bone marrow. The diagnosis was
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extramedullary plasmacytoma with dissemination. The patient was treated with monthly cycles of Melphalan and Prednisone with good response. In March 1973, serum protein and bone marrrow studies were normal. No significant change in the nasopharyngeal mass had occurred. From April to September 1973, the patient was lost to follow-up only to return because of nasal obstruction, redness and swelling of the right face and rapidly enlarging cervical lymph nodes. Examination in this Radiotherapy Department revealed swelling and redness of the right face, a right exophthalmos, bilateral cervical lymph nodes measuring up to 7 cm in diameter, and a nasopharyngeal mass that filled the nasopharynx. Laboratory studies showed elevated serum proteins. A bone marrow aspiration was normal. Radiographs demonstrated additionally, opacification of the right antrum with destruction of the anterior and lateral walls (Figs. 1 and 2) and an osteolytic lesion in the body of sixth cervical vertebra. 6oCo therapy (6700 rad tumor dose in 33 treatments over 50 days) was delivered to the nasopharynx, anterior ethmoids and right antrum. Simultaneous therapy was administered to the neck and C-6 vertebra-left neck (6000rad in 30 treatments over 42 days) right neck (5000rad in 42 days) and C-6
Fig. 1. A large mass filling completely the nasopharynx.
Extramedullary
pasmacytoma
Fig. 2. Opacification
of the upper respiratory
passages 0 Z. PETROVKH
of the right antrum with bone destruction
(5500rad in 42 days). All tumor regressed completely (Figs. 3 and 4). Melphalan and Prednisone therapy was instituted in December 1973, and completed in October 1974. The patient was clinically free of tumor more than 4 years after initiation of therapy. DISCUSSION Seven cases of plasmacytoma arising in the upper respiratory and digestive tracts have been presented. The presenting characteristics of this group of patients fits the existing data published in the literature.3.‘5X’8 The duration of symptoms (1 month to 2 years), age at diagnosis (34 years to 74 years with a median of 59 years) pattern of presenting symptoms
et al.
727
of the lateral wall.
(nasal obstruction 4, bleeding 1, hoarseness 1) and prognosis are similar to the data reported by others. Dissemination occurs in one-third, lymph node metastases are present in one-third and more than one-half of patients survive 5 years or longer.‘.“.” The observed patterns of tumor extension and metastases closely correlates with those of other tumors arising in the upper respiratory and digestive tracts. The radiotherapy treatment techniques utilized in this group of patients closely resembles that used for other tumor types, and with similar results. A tumor dose of 6000-8000rad was required to achieve local control. Patients who recurred locally or who had persistent disease at the end of radio-
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Fig. 3. Lateral view of nasopharynx. Upper view obtained during the radiotherapy in November 1973, shows partial resolution of the large nasopharyngeal mass. Lower view obtained in January 1976, shows complete resolution of tumor mass. therapy were given additional treatment. Although the reason is not clear for the success achieved with suppliment doses of 2200-3400rad for persistent or recurrent disease, it is postulated that this observed phenomenon is probably a tumor bed effect. It is a common experience to radiotherapists that such doses given as preliminary treatment are virtually ineffectual in controlling this tumor; yet for supplemental treatment of persistence and recurrence these modest doses have been sufficient to control the tumor in previously irradiated sites. It is apparent in these 7 patients that the use of
radiotherapy as primary treatment has achieved excellent control of tumor with preservation of the function and appearance of the patient. We feel, therefore, that although surgery has achieved similar tumor control and survival, radiotherapy is preferable as the primary modality of treatment in patients with localized extramedullary plasmacytoma.6~g~‘9~20 Alexanian et al. have demonstrated the usefulness of chemotherapy in treatment of multiple myeloma in some patients.’ We have substantiated this in patient 7 who achieved a long term tumor free interval when his systemic disease was treated with Melphalan and
Extramedullary
Fig. 4. Views of maxillary
pasmacytoma
antrum.
of the upper respiratory
SUMMARY patients arising in the
toma ported. (2) Either management
primary provides
with extramedullary plasmacyupper respiratory tract are resurgical equivalent
PETROVICH et al.
Two studies of the antrum reveal no evidence restoration of the antral wall.
Prednisone. Patient 5 survived nearly 5 years after dissemination with combined chemotherapy-radiotherapy treatment. It is our opinion that patients with and those with dissemination nodal metastases, should have treatment which includes chemotherapy.
(1) Seven
passages 0 Z.
or radiotherapy control of disease.
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of tumor mass and
(3) Radiotherapy provides superior functional and cosmetic end results. (4) Metastasis to regional lymph nodes increase the risk of dissemination. (5) Frequent long term survival in this group of patients warrants appropriate and intensive therapy. (6) Chemotherapy is of value when dissemination is present. We feel that radiotherapy is the modality of choice for tumor control, preservation of function and cosmetic end result in the management of extramedullary plasmacytomas of the upper respiratory passages.
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2. 3. 4.
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R., Bonnet, J., Gehan, E., Haut, A., Hewlett, J., Lane, M., Monto, R., Wilson, H.: Combined chemotherapy for multiple myeloma. Cancer 30: 382-389, 1972. Anderson, P.R.: Extramedullary plasmacytomas. Acta Radiol. 32: 363-374, 1949. Carson, C.P., Ackerman, L.V., Maltby, J.D.: Plasma cell myeloma. Am. J. Clin. Path. 25: 849-888, 1955. Castro, E.B., Lewis, J.S., Strong, E.W.: Plasmacytoma of paranasal sinuses and nasal cavity. Arch. Otofaryngal. 97: 326-329, 1973. Dolin, S., Dewar, J.P.: Extramedullary plasmacytoma. Am. .l. Pathol. 32: 83-103, 1956.
6. Ewing, M.R., Foote, Jr., F.W.: Plasma cell tumors of the mouth and upper air passages. Cancer 5: 499-513, 1952. 7. Fishkin, B.G., Spiegelberg, H.L.: Cervical lymph node metastasis as the first manifestation of localized extramedullary plasmacytoma: Cancer 58: 1641-1644, 1976. 8. Fishkin, B.G., Spiegelberg, H.L.: Extramedullary (soft tissue) plasmacytoma (Abstract). Am. J. Clin. Path. 59: 150, 1973. 9. Gromer, R.C., Duvall, A.J.: Plasmacytoma of the head and neck. J. Laryngol. Otol. 87: 861-872, 1973. 10. Hellwig, C.A.: Extramedullary plasma cell tumors as
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observed in various locations. Arch. Path. 36: 95-111, 1943. Helmus, C.: Extramedullary plasmacytomas. Laryngoscope 74: 553-358, 1%4. Kutcher, R., Ghatak, N.R., Leeds, N.E.: Piasmacytoma of the calvaria. Radiology 113: 111-115, 1974. Osserman, E.F., Farhangi, M.: Plasma cell myeloma. In Hematology, ed. by Williams, W.J., Beutler, E., Ersler, A.J., Roudles, R.W. New York, McGraw-Hill, 1972, pp. 960-962. Poole, A.G., Marchetta, F.C.: Extramedullary plasmacytoma of the head and neck. Cancer 22: 14-21, 1968. Rawson, A.J., Eyler, P.W., Horn, Jr., R.C.: Plasma cell tumors of the respiratory tract. Am. J. Path. 25: 445461, 1950.
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16. Schridde, H.: Weitere Untersuchungen Uber Die Kornelungen Der Plasmazellen Zentrabl. E Allg. Path. Path. Anat. 16: 433435, 1905. 17. Stone, H.B., Cole, T.B.: Extramedullary plasmacytomas of head and neck. South. Med. J. 64: 1386-1388, 1971. 18. Stout, A.P., Kenney, F.R.: Primary plasma cell tumors of the upper air passages and oral cavity. Cancer 2: 261-277, 1949. 19. Todd, I.D.H.: Treatment of solitary plasmacytoma. Clin. Radiol. 16: 395-399, 1%5. 20. Webb. H.E., Harrison, E.G., Masson, J.K., Remine, W.H.: Extramedullary myeloma (Plasmacytoma) of the respiratory tract and oropharynx. Cancer 15: 11421155. 1%2.
