Reticulum-cell sarcoma of the jaws

Reticulum-cell sarcoma of the jaws Report of two cases and comparison and other countries

of incidence

in Japan

Shi-Long Lian, D.D.S., * Tetsuo Nagai, D.D.S., ** Hirofumi Kawasaki, D.D.S., ** Kazuso Sakaizumi, D.D.S., Dr.Med. SC., *** and Yasuo Nakamura, D.D.S., Dr.Med.Sc., **** Tokyo, Japan KEIO

UNIVERSITY

SCHOOL

OF MEDICINE

The two cases presented involved a sarcoma which may arise primarily in the gingivae and mandible. These sarcomas were treated with radiation and chemical antitumor agents. The primary lesions showed complete remission, but later there was rapid extension and metastasis to many vital organs. A review of the literature demonstrates the lesion’s occurrence in the head and neck region in Japan and other countries.

R

eticulum-cell sarcoma is relatively rare and is seldom recognized in the jaws, although it is the most frequently occurring sarcoma in the head and neck region. Reticulum-cell sarcoma is radiosensitive, but radiation therapy is not quite sufficient to control the tumor. In Japan the 5-year survival rate with radiotherapy alone is about 50 percent in Stage 1, but when radiotherapy is combined with chemical agents the survival rate can rise to 70 percent. CASE 1

A @year-old man came to our departmenton March 12, 1976, with a chief complaint of pain and swelling in the mandibular left molar region and left cheek. In November, 1975,the patient noted a numb sensationin the left lower lip. At the end of February, 1976, he visited a local dental office with a week-long history of pain and swelling in the left lower molar area. Despite local irrigation and a l-week course of antibiotics, the symptomsdid not improve. The patient was referred to our department for further examination. Past medical history

The patient had a normal childhood and adult life. The remainder of the past history, family history, and review of systemswas noncontributory. *SeniorStaff, Departmentof Dentistry and Oral Surgery. **Instructor, Department of DentistryandOral Surgery. ***AssistantProfessor,Departmentof DentistryandOral Surgery. ****Chairman and Professor,Departmentof Dentistry and Oral Surgery. 110

Physical examlnation and oral findings

Physical examination revealed a moderately developed, moderately well-nourished man who was alert and in no distress. Two small bean-sizedsubmandibular nodes were palpable bilaterally, and there was a diffuse facial swelling with tendernessfrom the left mandibular molar extending to the left mandibular angle region. The remainder of the physical examination was noncontributory. Intraoral examination revealed a diffuse ulcerative swelling involving the gingivobuccal mucosaof the three lower left molars (Fig. 1). A periapical radiograph appearednormal, but there was an exceptional loss of lamina dura of the lower left second molar. The extraoral roentgenologic examination of the left mandible showed a few small moth-eaten defects involving the mandibular angle (Fig. 2). A biopsy was performed, and the pathologic interpretation was malignant lymphoma, possibly reticulum-cell sarcoma. Laboratory examination

Routine laboratory studies revealed a normal blood chemistry, hemogram,and urinalysis. Chest and skull radiographs were grossly normal. Results of a bone marrow aspiration were within normal limits. Clinical course

The patient was admittedto the hospital on April 10, 1976. Following consultation with the hematology and radiotherapy clinics, he was started immediately on a regimen of 2 mg. vincristine intravenously once a week and 50 mg. Endoxan and 30 mg. prednisolone by mouth once a day. In the meantime, a mantle technique was employed for radiotherapy with a 6 mev. linear acceleratorto deliver a weekly tumor dose of 1,200rads. After five days of combined treatmentsthe tumor 0030-4220/80/080110+06$00.60/0

0 1980 The C. V.

MosbyCo.

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Fig. 1. Case 1. Intraoral appearanceof the tumor before treatment.

decreasedin size, and there was complete remission a few days later (Fig. 3). The patient’s progressin the hospital was uneventful. After he had been given a total doseof 8 mg. vincristine, 1,350mg. Endoxan, 8 10mg. prednisolone, and 3,000 radsof irradiation over a 3week period, he was advised to undergo a courseof 4,000 tads of irradiation. He refusedbecauseof hair loss. He was dischargedwithout evidenceof diseaseon May 13, 1976. After discharge he was followed monthly and chemotherapy with Endoxan and prednisolone was continued. The patient was free of diseaseabout 10 months after discharge. On March 17, 1977, he was examined in the Outpatient Department, where a tumor massthe size of a pigeon egg was found in the anterior part of his neck, in the same position as the left lobe of the thyroid. A metastatic lesion was suspected.One week later the patient was hospitalized on an emergency basis with severe diarrhea and abdominal extension. Two days later he was referred to the radiotherapy and hematology clinics for further treatment. Whole-body scintillations with radioisotopes rslI, 201T1g9mTc and ‘j7Ga were performed. The 13’1scintigram revealed a defect image in the left lobe of the thyroid, and the *‘IT1 scintigram showed an abnormal accumulation in the left lobe of the thyroid. Thus, it was interpreted that the left lobe of the thyroid was invaded by the tumor (Fig. 4). A %Tc diphosphatebone scintigram showed an abnormal uptake in the left mandibular angle (Fig. 5). A 67Gatumor scintigram showed abnormal activity in the lower abdomen and moderatedactivity in the left kidney and heart. An angiogram of only the left kidney showed an abnormal architecture of the blood vessels. A para-aortic lymphogram was noncontributory. Malignant lymphoma cells were found in the aspirated ascites. The tumor was widespread and appearedout of control. The patient died on Aug. 14, 1977. Autopsy reports described a histocytic differentiated reticulum-cell sarcomainvasion of the left lobe of the thyroid, both lungs, myocardium and pericardium, the entire digestive system, and almost all deep lymph nodes. Tonsils, thymus, spleen, and skin revealed no evidence of metastasisor infiltration. No recurrence

111

Fig. 2. Case 2. Left lateral oblique radiograph of mandible

showing multiple moth-eatendefects in the ramus and body.

Fig. 3. Case 1. Intraoral appearanceafter treatment.

of the primary lesion of the mandible and gingiva around the lower left second and third molars was evident. Cese 2 A 64year-old man was referred to us on Nov. 27, 1973, becauseof a swelling in the medial jaw, lip, and gingivae. History of present illness

A Looseningof the anterior teeth and a swelling of the anterior labial gingivae were noticed by the patient in March, 1973.One month later swelling and pain madehim unable to wear his partial denture (Fig. 6). Past history

The patient had had a normal childhood and adult life, with no family history of malignant diseases.He was hospitalized with malaria for one year during World War 11when he was serving in the JapaneseArmy. On Nov. 27, 1973,during his first visit to our department, physical examination revealed a moderately developed, moderately well-nourished man who was alert and in no distress,The remainderof the examination was noncontributory.

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Fig. 4. Case 1. A, A *OIT1scintigram showing abnormal accumulation in the left lobe of the thyroid. B, A 1311

scintigram showing a defect in the left lobe of the thyroid. Oral findings

Swelling in the mental region was noted. Oral hygiene was poor, with a nontender 38 by 26 mtn. hard exophytic mass extruding from the gingivae of the 11234region. The following teeth were missing: 76521/. The circumscribed swelling had no definite area of fluctuance. The periapical dental x-ray film showed deep decay with destruction of alveolar bone of the lower left canine; the lateral incisor was moderately mobile but not painful to percussion. Laboratory examination

With the exception of occult blood in the stools, laboratory findings were normal. Roentgenogramsof the skull and chest revealed no pathologic changes. Clinical course

The patient was admitted to the hospital on Dec. 4, 1973. Two days after he was admitted an operation for removal of a biopsy specimen and exposure of the superficial temporal artery for continuous arterial infusion was performed because malignant disease was strongly suspected.The patient was startedon BAR therapy-B (BudR a radiosensitizer), A (antimetabolite), and R (radiation)-on December 4. A dose of BudR, 500 mg. per day, and 5-FU, 250 mg. per day, was continuously infused into the artery with an automatic pump infuser. Radiotherapy began on December 6, with a weekly tumor dose of 1,200 tads. On December 7 the pathologist’s report described a poorly differentiated histiocytic reticulum-cell sarcoma. The BAR therapy was continued until December 24 and then suspendedbecause of severe diarrhea and high-grade fever with chills, a sequel of chemotherapy. When the treatment was halted, the total dose was 10 Gm. BudR, 5.0 Gm. 5-FU, and 3,000 rads of irradiation.

The tumor decreasedin size from December8, and was in complete remission 10 days later. Progress remained unevent-

ful until the end of December (Fig. 7). The patient died on

June 15, 1974, of stomach, lung, and other distant metastases. No autopsy was performed. REVIEW OF THE LITERATURE AND DISCUSSION The classification of malignant lymphoma is still a controversial subject. Historically, two broad categories of malignant lymphoma have been recognized: ( 1) Hodgkin’s disease and (2) non-Hodgkin’s malignant lymphoma, as malignant lymphoma, lymphosarcoma, and reticulum-cell sarcoma. Until now, nonHodgkin’s lymphomas have been classified by the Rappaport’ system, in which the tumor is categorized by its histologic pattern as nodular or diffuse. Tumor cells are further distinguished by their cellular origin and by the degree of cellular differentiation. For example, a lymphoma may be described as lymphocytic and well-differentiated, lymphocytic and poorly differentiated, mixed-cell (lymphocytic and histocytic), or undifferentiated reticulum-cell sarcoma. Both of our cases involved differentiated histocytic reticulum-cell sarcoma. The primary reticulum-cell may be found anywhere in the body, and therefore it is not surmising to find reticulum-cell sarcoma in organs and systems other than lymph nodes. It is rare for reticulum-cell sarcoma to appear initially in the mucosa and submucosa of the head and neck, but occasionally it occurs in Waldeyer’s ring (tonsil and nasopharynx) or in the sinuses. The reported incidence of lymphosarcoma, and more specifically reticulum-cell sarcoma, in the head and neck shows great variability in different collected series.

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113

Case2. Intraoralappearance. Notebulgingsubmucous swellingsof the alveolus of 1234 before treatment.

Fig. 6.

Fig. 5. A ggmTc diphosphatebonescintigramshowingabnormal accumulationin the left mandibularbody andramus.

Masaki and colleagues2reported that of 429 malignant lymphomas seenfrom 1961through 1975, 296 (69 percent) were reticulum-cell sarcomas(Table I); 222 (75 percent) of these were found in the head and neck, and 145(65 percent) were localized in Waldeyer’s ring. Otsuka3reported that 76 reticulum-cell sarcomas, out of 94 malignant lymphomas, occurred in Waldeyer’s ring and 40 (52 percent) of these were localized in the tonsil. Matsubara and associates4reported an analysis of fourteen cases( 1965 to 1975) of extranodal malignant lymphomas originating from the oral region which disclosed that 10 (7 1 percent) were reticulum-cell sarcoma but only one occurred primarily in the mandible. In the radiotherapeutic clinic of Keio University Hospital from 1966through 1970, twenty-three patients with malignant lymphoma in the head and neck region accepted radiotherapy. Twenty-one of the tumors (91 percent) were reticulum-cell sarcoma, and 10 (47 percent) originated in the tonsil, but none was found in the lower jaw. From 1971 through 1976 70 malignant tumors were treated in our department; 4 were malignant lymphomas and 2 of 4 sarcomaswere reticulumcell sarcomas.One originated in the mandible, and the other occurred in the lower gingiva. Looser and Kuhen5 reported that in a study of 49 primary tumors of the mandible seen from 1937 to 1974, they found only 4 reticulum-cell sarcomas. Steg, Dahlin, and Gores6re-

Fig. 7.

Case2. Normal appearance of the anterioralveolar

mucosa after 3.000 rad irradiation.

ported 47 casesof lymphosarcomaof the mandible and maxilla, and 14 (30 percent) of these tumors were reticulum-cell sarcomas.Only 3 of them involved the mandible. Pindborg’s’ review of the files of the Danish Cancer Registry estimated 11 reticulum-cell sarcomas in 43 jaw sarcomas,and only 1 was found in the mandible. In recent years, geographic variations in the prevalence of the various types of malignant lymphoma have generatedconsiderable interest. The geographic distribution of reticulum-cell sarcomamay be variable. Reports of this tumor are more commom in European clinics.3, 8 Only 6 casesof reticulum-cell sarcoma occurred among 1,000casesof cancer of the nasopharynx in Taiwan, as reported by Yeh.g Zange and Scholtz,” in Germany, found 13 patients (4 percent) with reticulum-cell sarcomaamong 320 patients with malignant tumors of the nose and paranasalsinuses. Of 281 lymphoreticular tumors registered by the Japanese cooperative group for the study of lym-

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Table 1.Representativeexperience with malignant lymphoma in Japan, the United States, and England Jupan Tumor

Akazaki”

Reticulum-cell sarcoma Lymphosarcoma Hodgkin’s disease Others*

Masaki et al.2

U.S.A.

143 (50.9%)

296 (69.2%)

127 (20.5%)

102 (18.7%)

64 (22.8%) 47 (16.7%) 27 (9.6%)

57 (13.3%) 33 ( 7.7%) 43 (10%)

220 (35.6%) 229 (37%) 42 (6.8%)

207 (39%) 206 (38.6%) 19 (3.7%)

I

England

*Other tumors include multiple myeloma, follicular lymphoma, Burkitt’s lymphoma, etc.

Table II. Reticulum-cell sarcoma/lymphosarcoma(RCS/LSA) ratios in the pharynx (modified from Otsuka3) Author

Year

Country

Pharynx Naso-pharynx

Yeh Lederman Schnohr Otsuka

1967 1961 1970 1970

China* England U.S.A. Japan

Tonsil

Rosenberg Pizzetti Barth Otsuka

1961 1951 1962 1970

U.S.A. Italy Germany Japan

Naso-oropharynx

Rosenberg Bang Gtsuka

1961 1969 1970

U.S.A. Italy Japan

Site

No. of lymphomas

RCS

LSA

RCSiLSA

II 34 27 21

6 20 11 17

5 14 5 4

1.2 1.4 2.2 4.3

56 63 10 50

22 56 9 40

34 7 1 8

0.6 8 8 5

91 282 94

37 246 76

54 36 15

0.6 6.8 5.1

*China: Taiwan, Republic of China.

Table III. Abbreviations of the chemotherapeuticagents COPP Cytoxan Oncovin = Vincristine Procarbazin Prednisolone VEMP Vincristine Endoxan 6-Mercaptopurine Prednisolone MOPP Nitrogen mustard Oncovin = Vincristine Procarbazine Prednisolone

MVPP Nitrogen mustard Vinblastine Procarbazine Prednisolone VEP Vincristine Endoxan Prednisolone

phoreticular neoplasms in 1969, 143 (50.9 percent) were reticulum-cell sarcomas, 64 (22.8 percent) were lymphosarcomas, 47 (16.7 percent) representedHodgkin’s disease,and 27 (9.6 percent) were follicular lymphomas.” Gall and Mallory,r2 of the United States, reported that the relative frequency percent in their study of 618 lymphoma cases was 20.5 percent for reticulum-cell sarcoma, 35.6 percent for lymphosarcoma, 37 percent for Hodgkin’s disease, and 6.8 percent for follicular lymphoma. The similar percentages in the study of 534 lymphoma cases in England reported by HancockI were

19.7 percent for reticulum-cell sarcoma, 39.8 percent for lymphosarcoma, 38 percent for Hodgkin’s disease, and 3.5 percent for follicular lymphoma (Table I). Reticulum-cell sarcomais the most prevalent form of malignant lymphoma in Japan, with a relative frequency (42 percent) that approachesthat of Hodgkin’s disease in western series (49 percent). Conversely, Hodgkin’s disease is the least frequently encountered form of lymphoma in Japan, with a relative frequency (20 percent) not far removed from reticulum-cell sarcoma (18 percent) in the west.12 Rosenberg and associates,14in the United States, showed a reticulum-cell sarcoma to lymphosarcoma ratio of 0.6 for tonsil and naso- and oropharynx. In Italy the ratio is 6.8, as reported by Banfi. In Japan Otsuka3reported a ratio of about 5 in the tonsil and 5.1 in the naso- and oropharynx (Table II). A comparison of these studies clearly showed a remarkable excess of reticulum-cell sarcomain Japan. It is suggestedthat thesegeographic differences may be related to the close interrelationships of lymphomas and genetically governed variations in host reactivity.12 Perhaps the genetic make-up of the Japanesedetermines a different responseof the organism to the same cancerogenicenvironmental stimuli. It is also possible that the Japaneseare exposed to a different set of environmental carcinogensthan are the other populations of the world.”

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The reticulum-cell sarcoma is radiosensitive, and radiation therapy is necessaryfor this disease. Wang and Fleischli15 recommendedthat initial therapy be in the form of radiation with a total doseof 4,500 to 5,000 roentgens over a 4 to 5week course, with a field including the regional nodes. Variant modalities of chemotherapy combined with radiation are highly recommended. The combined chemotherapy, such as VEP, VEMP, MOPP, and MVPP, etc.3*’ (Table III), and the combined chemotherapy and radiation therapy raises the S-yearsurvival rate to 70 percent instead of 50 percent for radiotherapy only in Stage 1 and 60 percent instead of 33 percent in Stage 2. When this tumor occurs intraorally, it has a relatively good prognosis and may be radiocurable when treated early. Local recurrenceis uncommon.16Reticulum-cell sarcoma of bone appears to be less serious than the soft-tissue form. The Armed Forces Institute of Pathology records a 40 percent median survival of 7 years for patients with reticulum-cell sarcomaof bone, whereas all those with the soft-tissue form died within 2% yeawl In one of our casesof sarcomain the gingiva there was a rapid distant metastasisafter initial radiotherapy. In the other casethere was a silent period of more than 1 year, followed by relapse with an acute and fatal course. Neither caseshowedevidence of malignancy in the primary site. SUMMARY

Reticulum-cell sarcomais rare in the lower jaw. Two patients with reticulum-cell sarcoma of the jaw were found among 70 patients with malignant tumors seen from 1971 through 1976. Both caseswere treated with combined radiation and multiple combination chemotherapy. Both tumors responded to the treatment, but after a period of silence they relapsed and ran an acute and fatal course. The patients died with widely disseminated disease, but in each case the primary site remained free of malignancy. Reticulum-cell sarcomais the most prevalent form of malignant lymphoma in Japan. This higher relative frequency of reticulum-cell sarcomais indeed the result of a lower frequency of the other types of malignant lymphoma, especially Hodgkin’s disease. These geographic differences may be related to the close interrelationships of the lymphomas as genetically governed variations in host reactivity.

Reticulum-cell sarcoma is treated by radiation and multiple combination chemotherapy, as are other non-Hodgkin’s lymphomas. The survival rates are dramatically improved with this treatment. REFERENCES 1. Raooaoort,H.: Tumors of the Hematopoietic system.In Atlas of T&or Pathology, Set III. Fast. 8, Washington. D.C., 1966, Armed Forces Institute of Pathology. 2. Masaki, N., Ikeda, H.,+and Shigematsu, Y.: The Influence of Chemotherapy on the Radiotherapeutic Management of NonHodgkin’s Lymphoma in Head and Neck, Jpn. J. Cancer Clin. 23: 1177-1181, 1977. 3. Otsuka, H.: Incidence of Malignant Lymphomas and Undifferentiated Carcinomasin the Pharynx, Saishin-Igaku 26: 937946, 1971. 4. Matsubara, S., et al.: Fourteen Casesof Malignant Lymphoma Originating From the Oral Region, Nippon Acta Radio]. 36: 693701, 1976. 5. Looser, K. G., and Kuhen, P. G.: Primary Tumors of the Mandible, Am. J. Surg. 132: 608614, 1976. 6. Steg, F. R., Dahhn, D. C., and Gore, R. J.: Malignant Lymphoma of the Mandible and Maxillary Region, ORAL SURG. 12: 128-141, 1959. 7. Pindborg, J. J.: The Incidence Rate of Jaw Sarcomasin Denmark, ORALSURG.14: 276279, 1961. 8. Larsen, R. R., Hill, G. J., Znd., and Ratzer, E. R.: ReticulumCell Sarcoma in Head and Neck Surgery, Am. J. Surg. 123: 338342, 1972. 9. Yeh, S.: A Histologic Classification of Carcinoma of the Nasopharynx With a Critical Review as to the Existence of Lymphoepithelioma, Cancer 15: 895-920, 1962 10. Zange, J., and Scholtz, H. J.: 25 Jahre Behandlung biisartiger Geschwiilste der Nase und Nebenhohlenin Jena und ihr Ergebnis, 2. Laryngol. Rhinol. Otol. 42: 613640, 1%3. 11 Akazaki, K., and Wakasa, H.: Frequency of Lymphoreticular Tumors and Leukemias in Japan, J. Natl. Cancer Inst. 52: 339343, 1974. 12 Anderson, R. E., Ishida, K., Li, Y., et al.: Geographic Aspects of Malignant Lymphoma and Multiple Myeloma; Select ComparisonsInvolving Japan,England and the United States,Am. J. Pathol. 61: 85-98, 1970. 13. Hancock, P. E. T.: Malignant Lymphoma, Clinico-Pathologic Correlation. In Raven, R. W. (editor): Cancer, London, 1958, Butterworth & Co., Ltd., vol. 4, pp. 412-428. 14. Rosenberg, S. A., Diamond, H. D., Jaslowitz, B., and Craver, L. F.: Lymphosarcoma,a Review of 1,269Cases,Medicine 40: 31-84, 1961. 15. Wang, C. C., and Fleischli, D. J.: Primary Reticulum-Cell Sarcoma of Bone With Emphasison Radiation Therapy, Cancer 22: 994998, 1968. 16. Halperin, S., and Williams A. C.: Reticulum-Cell Sarcoma of the Mandible, ORALSURG.28: 32-35, 1969. 17. Taylor, C. G, , Alexander, R. F., and Kramer, H.S ., Jr.: Primary Reticulum Cell Sarcoma of the Mandible; Report of a Case, J. Oral Surg. 28: 218-221, 1970. Reprint requests to:

Dr. Shi-Long Lian Department of Dentistry and Oral Surgery School of Medicine, Keio University #35 Shinanomachi, Shinjuku, Tokyo, Japan