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Circumstances favoring jaw tumors in Burkitt's lymphoma
Medical
Hypotheses
12 : 331-340
CIRCUMSTANCES FAVORING JAW TUMORS IN BURKITT’S Mortimer Lorber, Georgetown and Dentistry, Washington,
University D.C., 20007
Schools
of
LYMPHOMA Medicine
ABSTRACT __--In Burkitt’s lymphoma, dental structures may provide the route for Epstein-Barr virus (EBV) in saliva to penetrate the jaws, thereby promoting tumor formation. In children, EBV could enter tooth sockets exposed following deciduous tooth loss and thereby contact jaw marrow lymphocytes stimulating neoplastic transformation. Marrow contact by EBV probably also occurs through carious teeth. Jaw tumors are rare in adults because their jaw marrow is no longer hematopoietic and so lacks the lymphoid substrate for the virus. jaw marrow lymphocytosis, as In adults, accompanies infectious mononucleosis and perhaps malaria, or which could develop around the roots of carious teeth having chronic periapical infection, could provide the substrate EBV could then contact the jaw marrow lymphocytes for EBV. when teeth are extracted and so favor jaw tumor development. Therefore, prevention of dental caries might reduce jaw tumor prevalence in Burkitt’s lymphoma except among children ages 6-13 whose jaw marrow would unavoidably become infected by salivary EBV when the latter is present at the time of debiduous tooth loss. INTRODLJCTLQN There is non-uniformity in the clinical picture of Burkitt’s lymphoma and the prevalence of antibodies to Epstein-Barr virus (EBV) in cases from different geographic areas. Jaw tumors are frequent in Africans (1) in whom EBV is usually present (2). Contrariwise, American Burkitt’s tumor is rare (31, EBV is generally absent (4), and jaw tumors are less common (5).
331
The hypothesis to be presented rests on the assumption that in many people EBV is causally related to Burkitt’s The reasoning would still apply if the lymphoma. etiological agent were another infectious one as long as it would exist in saliva, as does EBV (6,7), and be able to gain access to the interior of the jaws, specifically the alveolar (tooth-supporting) processes where the tumors begin I,\ HYPOTHESIS The postulated mechanism for entry of the virus into EBV the jaws involves the teeth and associated structures. could enter the bone through carious teeth, as well as when deciduous teeth are shed or deciduous and permanent ones extracted. Jaw tumor formation also requires that lymphocytes, the tumor progenitors (81, be present in the bone. This would largely depend on an individual’s age and oral hygiene. DISCUSS_Ia Six lymphoma
clinical will be
characteristics discussed in
of terms
jaw tumors in Burkitt’s of the hypothesis.
1) Frequent_Jl?_ul~p~~~~y~ Of 557 patients seen in Uganda, 26% had a single jaw tumor, 21.5% had multiple ones, and 7.5% had them in all four quadrants (9). The multiplicity may reflect involvement of dental structures in more than one area of the mouth as commonly occurs with dental disease and tooth loss. 2) Particu_l_ar_ occurrence in ch_i.ldren: Burkitt (IO) described the incidence of jaw involvement in Uganda as varying inversely with the age of the patient. Only one of his cases was under age 2. Twenty-five percent of children less than age three had jaw tumors, and at age three all did. The peak incidence was ages 3-8. It then decreased to 30% at age 12 and to only 15% from age 15 on. The peak age groups are when the deciduous teeth are present. These teeth erupt between ages 2-6 and are shed to be succeeded by the permanent teeth between ages 6-13. It is probable that EBV could penetrate the jawbones through the pulps of carious deciduous teeth. Just as carious teeth contain bacteria which can traverse the dentinal tubules (11) and the pulp to form a dentoalveolar abscess at the root apex which are smaller than bacteria, may likewise (121, viruses, reach the interior of the jaws via dental pathways. Lymphoid cells are a reservoir of EBV (13) and the substrate for viral growth (8). Their presence is required for tumor formation. Young children would be particularly likely to develop jaw tumors because their jaw marrow is
332
hematopoietic (14) and should contain lymphatic nodules as exist in the hematopoietic marrow of adults (15). In children ages 6-13, the shedding of deciduous teeth (16) would permit saliva to bathe the alveolus (tooth socket) and enter the adjacent marrow which should still have hematopoietic areas including lymphoid tissue. Thus, these older children with EBV would be susceptible to jaw tumor development. Among Africans with Burkitt’s lymphoma, jaw tumors occurred in 57% of children and 30% of adults (9). This disparity presumably reflects the greater prevalence of lymphocytes in the hematopoietic jaw marrow of children, (141, in contrast to normal adults. That and the greater prevalence of dental caries in childhood (17), together with the loss of deciduous teeth, all predispose children with salivary EBV to jaw tumor formation. even though Therefore, dental tissues do not play a role in the pathogenesis of the tumor (181, they may serve as pathways by which EBV can reach lymphoid tissue when it is present within the jaws. The dental status of Burkitt’s cases is rarely recorded Two children with carious teeth were in the literature. noted to have had jaw tumors ( 18,191, but a 14 year old boy had a mandibular tumor despite no teeth being carious (20). Nevertheless, the shedding of deciduous teeth a year or two previously may have permitted marrow invasion and subsequent Consonant with this probability is the tumor development. reported length of the incubation period for Burkitt’s lymphoma being said to range from more than nine months (21) to as long as two years following EBV infection (22). eruption of teeth does not predispose to In contrast, neoplasia because the enamel cuticle covering each emerging Thus, dental crown fuses with the overlying gingiva (23). there is no break in mucosal continuity through which saliva containing EBV could penetra.te the deeper tissues. 3 1 &e_di_lection__for_ J&e_ p_o-s_t_eri~~~n.di-b-1-e.: The SP a r i n g of the anterior jaw region (24) can be explained by normal In both the deciduous and permanent dental anatomy. dentitions, anterior teeth are single rooted and molars are mu1 tirooted. Bicuspids are present only in the permanent dentition and all except the maxillary first are single extensive caries in molars will rooted (25). Thus, eventually involve the pulp canals of the two or three roots of each tooth. EBV could thereby penetrate them and contact the appreciable volume of alveolar bone surrounding those multiple roots in the posterior region of both jaws. By contrast, anterior teeth and bicuspids have smaller crowns. Therefore, when carious, less saliva is likely to enter their smaller pulp chambers and their usually single roots. This would result in fewer EBV particles contacting less jaw marrow than in the case of the molar teeth. These
333
differences explain the sparing likewise suggest that a threshold or both is necessary lymphocytes,
of
the anterior jaw (24) amount of virus, for tumor formation.
and
4) Occasional presence i.n_~&,lJs_: Despite the normal paucity (26) or even lack (27) of hematopoietic marrow in the jaws of older children and adults, some develop In Africans of such ages (91, characteristic jaw tumors. jaw tumors were not uncommon, being present at autopsy in 30% of 23 adult cases. Their formation would require the This presence of lymphocytes in adult jaw marrow. development may occur in individuals having hyperactive marrow attempting to compensate for increased hemolysis such as of ten accompanies malaria. Erythropoiesis requires helper T cells to make burst-promoting activity (28). The helper T such people cells would also stimulate B lymphocytes. Thus, would have an active lymphoid substrate for EBV in their jaws and so, in the presence of salivary EBV, be predisposed to jaw tumor development. An alternative or accompanying reason for the geographic association of Burkitt’s lymphoma with malaria (29) may be that malaria causes immunosuppression, particularly of antibody responses (30). That might reflect interference with the maturation of the B many immature B cells would be present lymphocytes. If so, and might give rise to a monoclonal outgrowth as believed by Magrath (31) to be common in children with certain lymphoma s . he attributes lymphomas to In older people, defects of the lymphocyte-activation pathway. EBV is also associated with infectious mononucleosis lymphocytosis of the jaw marrow In such cases, (IM) (6). If such an might accompany the peripheral lymphocytosis. individual had one or more teeth extracted, EBV-containing contact jaw lymphocytes saliva (7) would enter the alveolus, Because oropharyngeal and stimulate their proliferation. EBV persists after infectious mononucleosis (321, EBV-positive people with chronic periapical infection should despite the great be at high risk for jaw tumors. Yet, frequency of those diseases, jaw tumors in American However, some have Burkitt’s lymphoma are uncommon (5). occurred (33,341. Among 20 American patients three were more in American adults may than 20 years of age (34). The rarity be because to develop jaw tumors a combination of salivary EBV and bone marrow lymphocytosis, as occurs during the acute stage of infectious mononucleosis (35,361, must occur in the jaws. Additional marrow lymphocytes accompanying chronic periapical infection (37) may be needed to reach a threshold amount. The former lymphocytes probably disappear reducing the likelihood when the acute stage of IM subsides, Oral surgeons often of subsequent jaw tumor formation. prefer to postpone elective tooth extraction in patients having pharyngitis such as accompanies infectious mononucleosis. Postponement of extraction until EBV and lymphocytes diminish may contribute to the rarity of adult
334
cases among non-Africans. If, however, there is extensive periapical infection, sufficient lymphocytes might be chronically present in the jaw marrow so that contact by EBV would be likely when teeth are extracted. This would be the case for people from all regions. Jaw tumors were a presenting 5 ) Geoara~h~_c- .!Liff_ere_n_c~sl manifestation in but 6.6% (38) and 10% (5) of American cases compared to 55% of those in Uganda (9). Among those in all stages of the disease, they were noted in 16.7% in the U.S.A. (5) compared to 76% in Ghana (39). Yet despite high titers of antibody to EBV, only 15% of Iraqi children had jaw involvement (40). This disparity in the association of EBV with jaw tumors suggests that additional factors are required for tumor development. Because the shedding of deciduous teeth is ubiquitous, the geographical differences in jaw tumor prevalence among EBV-positive populations may reflect geographical variations in dental care and the incidence of dental caries due to differences in oral fluoride content of drinking water, etc. hygiene practices, The poor access to dental care of residents of African villages may well be a major contributory factor to their high frequency of jaw tumors. There were no presenting jaw tumors in a Danish series in which EBV antibody was uncommon (411, presumably because Therefore, the infectious agent was absent from the saliva. opening of paths to the interior of the jaws by extensive or the shedding or extraction of teeth could not caries, in Japan, al though EBV favor tumor development. However, antibody is rare and dentistry available, jaw tumors occurred in 91% of the cases and their response to suggesting another etiological chemotherapy was poor (42)) Other differences may exist. For agent for their lymphomas. Indian and Chinese residents of Singapore develop example, EBV infections at dissimilar ages and have different perhaps deciduous teeth antibody titers (43). In addition, are not given proper dental care by certain groups because de-The (44) postulated they are viewed as unimportant. environmental factors being necessary for tumor formation because the oncogenic potential of EBV is rarely realized. Genetics (45) and immune characteristics may provide the required background for the presently discussed dental and hematological factors and may contribute to the geographic differences in jaw tumor development. 6 1 Possible_ relationship _t_o_sa.li.ya_r_y__g.lan_ds.: The belief that the tumors arise in the jawbone (I 1 is not unanimous. Niederman .& a.l (7) stated EBV spread contiguously “from salivary glands to adjacent marrow of the mandible where Lehner oncogenic transformation of lymphocytes occurs.” (18) proposed a neoplastic parotid focus extending along blood vessels and masticatory muscles to the jawbones. However, if tumor arose in the salivary glands, the earliest
335
bony lesions should be along the posterolateral portions of both jaws, areas overlain by the parotid glands (18) and along the inferior border of the mandible where the submandibular and sublingual salivary glands are situated. Yet, the tumor initially involves the opposite surface containing the alveolar processes (1). This disparity suggests that if salivary glands are initially involved, only the parotids are significantly affected and tumor must somehow penetrate extensive soft tissues and bone to reach a specific and distant area of the jaw. The extensive ravages observed at autopsy (7,181 undoubtedly mask the initial changes so the direction of tumor progression cannot be stated retrospectively with confidence. Therefore, primary reliance should be placed on observations made early in the course of the disease (I) rather than terminally. CONCLUSIONS It is hoped that these hypotheses will encourage pathologists to examine otherwise normal accident victims to learn the distribution and cellularity of bone marrow present in the jaws at different ages. Attempts should be made to ascertain the lymphocyte content in the jaws of individuals with infectious mononucleosis and to study the It is locations of early jaw lesions of Burkitt’s lymphoma. important to learn whether there is accompanying salivary gland involvement and whether jaw tumors ever develop before six months of age when the first deciduous teeth erupt and might become carious. If such cases exist, they would indicate that jaw tumors could form in the absence of the postulated dental pathways. Detailed records should be made of the dental status of individuals with Burkitt’s jaw tumors to learn whether the presently postulated chain of events is plausible. It contact frequency typical
is of
believed that the dental pathways that permit EBV with lymphocytes in the jaws explain the of jaw tumors in Burkitt’s lymphoma and the absence of such tumors in non-cranial bones (22).
A corollary to this hypothesis is that prevention of dental caries could reduce jaw tumor formation in Burkitt’s lymphoma in all but those unfortunate children in whom the virus enters the jaw marrow when their deciduous teeth are shed. REFERENCES 1.
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Hypotheses
12 : 331-340
CIRCUMSTANCES FAVORING JAW TUMORS IN BURKITT’S Mortimer Lorber, Georgetown and Dentistry, Washington,
University D.C., 20007
Schools
of
LYMPHOMA Medicine
ABSTRACT __--In Burkitt’s lymphoma, dental structures may provide the route for Epstein-Barr virus (EBV) in saliva to penetrate the jaws, thereby promoting tumor formation. In children, EBV could enter tooth sockets exposed following deciduous tooth loss and thereby contact jaw marrow lymphocytes stimulating neoplastic transformation. Marrow contact by EBV probably also occurs through carious teeth. Jaw tumors are rare in adults because their jaw marrow is no longer hematopoietic and so lacks the lymphoid substrate for the virus. jaw marrow lymphocytosis, as In adults, accompanies infectious mononucleosis and perhaps malaria, or which could develop around the roots of carious teeth having chronic periapical infection, could provide the substrate EBV could then contact the jaw marrow lymphocytes for EBV. when teeth are extracted and so favor jaw tumor development. Therefore, prevention of dental caries might reduce jaw tumor prevalence in Burkitt’s lymphoma except among children ages 6-13 whose jaw marrow would unavoidably become infected by salivary EBV when the latter is present at the time of debiduous tooth loss. INTRODLJCTLQN There is non-uniformity in the clinical picture of Burkitt’s lymphoma and the prevalence of antibodies to Epstein-Barr virus (EBV) in cases from different geographic areas. Jaw tumors are frequent in Africans (1) in whom EBV is usually present (2). Contrariwise, American Burkitt’s tumor is rare (31, EBV is generally absent (4), and jaw tumors are less common (5).
331
The hypothesis to be presented rests on the assumption that in many people EBV is causally related to Burkitt’s The reasoning would still apply if the lymphoma. etiological agent were another infectious one as long as it would exist in saliva, as does EBV (6,7), and be able to gain access to the interior of the jaws, specifically the alveolar (tooth-supporting) processes where the tumors begin I,\ HYPOTHESIS The postulated mechanism for entry of the virus into EBV the jaws involves the teeth and associated structures. could enter the bone through carious teeth, as well as when deciduous teeth are shed or deciduous and permanent ones extracted. Jaw tumor formation also requires that lymphocytes, the tumor progenitors (81, be present in the bone. This would largely depend on an individual’s age and oral hygiene. DISCUSS_Ia Six lymphoma
clinical will be
characteristics discussed in
of terms
jaw tumors in Burkitt’s of the hypothesis.
1) Frequent_Jl?_ul~p~~~~y~ Of 557 patients seen in Uganda, 26% had a single jaw tumor, 21.5% had multiple ones, and 7.5% had them in all four quadrants (9). The multiplicity may reflect involvement of dental structures in more than one area of the mouth as commonly occurs with dental disease and tooth loss. 2) Particu_l_ar_ occurrence in ch_i.ldren: Burkitt (IO) described the incidence of jaw involvement in Uganda as varying inversely with the age of the patient. Only one of his cases was under age 2. Twenty-five percent of children less than age three had jaw tumors, and at age three all did. The peak incidence was ages 3-8. It then decreased to 30% at age 12 and to only 15% from age 15 on. The peak age groups are when the deciduous teeth are present. These teeth erupt between ages 2-6 and are shed to be succeeded by the permanent teeth between ages 6-13. It is probable that EBV could penetrate the jawbones through the pulps of carious deciduous teeth. Just as carious teeth contain bacteria which can traverse the dentinal tubules (11) and the pulp to form a dentoalveolar abscess at the root apex which are smaller than bacteria, may likewise (121, viruses, reach the interior of the jaws via dental pathways. Lymphoid cells are a reservoir of EBV (13) and the substrate for viral growth (8). Their presence is required for tumor formation. Young children would be particularly likely to develop jaw tumors because their jaw marrow is
332
hematopoietic (14) and should contain lymphatic nodules as exist in the hematopoietic marrow of adults (15). In children ages 6-13, the shedding of deciduous teeth (16) would permit saliva to bathe the alveolus (tooth socket) and enter the adjacent marrow which should still have hematopoietic areas including lymphoid tissue. Thus, these older children with EBV would be susceptible to jaw tumor development. Among Africans with Burkitt’s lymphoma, jaw tumors occurred in 57% of children and 30% of adults (9). This disparity presumably reflects the greater prevalence of lymphocytes in the hematopoietic jaw marrow of children, (141, in contrast to normal adults. That and the greater prevalence of dental caries in childhood (17), together with the loss of deciduous teeth, all predispose children with salivary EBV to jaw tumor formation. even though Therefore, dental tissues do not play a role in the pathogenesis of the tumor (181, they may serve as pathways by which EBV can reach lymphoid tissue when it is present within the jaws. The dental status of Burkitt’s cases is rarely recorded Two children with carious teeth were in the literature. noted to have had jaw tumors ( 18,191, but a 14 year old boy had a mandibular tumor despite no teeth being carious (20). Nevertheless, the shedding of deciduous teeth a year or two previously may have permitted marrow invasion and subsequent Consonant with this probability is the tumor development. reported length of the incubation period for Burkitt’s lymphoma being said to range from more than nine months (21) to as long as two years following EBV infection (22). eruption of teeth does not predispose to In contrast, neoplasia because the enamel cuticle covering each emerging Thus, dental crown fuses with the overlying gingiva (23). there is no break in mucosal continuity through which saliva containing EBV could penetra.te the deeper tissues. 3 1 &e_di_lection__for_ J&e_ p_o-s_t_eri~~~n.di-b-1-e.: The SP a r i n g of the anterior jaw region (24) can be explained by normal In both the deciduous and permanent dental anatomy. dentitions, anterior teeth are single rooted and molars are mu1 tirooted. Bicuspids are present only in the permanent dentition and all except the maxillary first are single extensive caries in molars will rooted (25). Thus, eventually involve the pulp canals of the two or three roots of each tooth. EBV could thereby penetrate them and contact the appreciable volume of alveolar bone surrounding those multiple roots in the posterior region of both jaws. By contrast, anterior teeth and bicuspids have smaller crowns. Therefore, when carious, less saliva is likely to enter their smaller pulp chambers and their usually single roots. This would result in fewer EBV particles contacting less jaw marrow than in the case of the molar teeth. These
333
differences explain the sparing likewise suggest that a threshold or both is necessary lymphocytes,
of
the anterior jaw (24) amount of virus, for tumor formation.
and
4) Occasional presence i.n_~&,lJs_: Despite the normal paucity (26) or even lack (27) of hematopoietic marrow in the jaws of older children and adults, some develop In Africans of such ages (91, characteristic jaw tumors. jaw tumors were not uncommon, being present at autopsy in 30% of 23 adult cases. Their formation would require the This presence of lymphocytes in adult jaw marrow. development may occur in individuals having hyperactive marrow attempting to compensate for increased hemolysis such as of ten accompanies malaria. Erythropoiesis requires helper T cells to make burst-promoting activity (28). The helper T such people cells would also stimulate B lymphocytes. Thus, would have an active lymphoid substrate for EBV in their jaws and so, in the presence of salivary EBV, be predisposed to jaw tumor development. An alternative or accompanying reason for the geographic association of Burkitt’s lymphoma with malaria (29) may be that malaria causes immunosuppression, particularly of antibody responses (30). That might reflect interference with the maturation of the B many immature B cells would be present lymphocytes. If so, and might give rise to a monoclonal outgrowth as believed by Magrath (31) to be common in children with certain lymphoma s . he attributes lymphomas to In older people, defects of the lymphocyte-activation pathway. EBV is also associated with infectious mononucleosis lymphocytosis of the jaw marrow In such cases, (IM) (6). If such an might accompany the peripheral lymphocytosis. individual had one or more teeth extracted, EBV-containing contact jaw lymphocytes saliva (7) would enter the alveolus, Because oropharyngeal and stimulate their proliferation. EBV persists after infectious mononucleosis (321, EBV-positive people with chronic periapical infection should despite the great be at high risk for jaw tumors. Yet, frequency of those diseases, jaw tumors in American However, some have Burkitt’s lymphoma are uncommon (5). occurred (33,341. Among 20 American patients three were more in American adults may than 20 years of age (34). The rarity be because to develop jaw tumors a combination of salivary EBV and bone marrow lymphocytosis, as occurs during the acute stage of infectious mononucleosis (35,361, must occur in the jaws. Additional marrow lymphocytes accompanying chronic periapical infection (37) may be needed to reach a threshold amount. The former lymphocytes probably disappear reducing the likelihood when the acute stage of IM subsides, Oral surgeons often of subsequent jaw tumor formation. prefer to postpone elective tooth extraction in patients having pharyngitis such as accompanies infectious mononucleosis. Postponement of extraction until EBV and lymphocytes diminish may contribute to the rarity of adult
334
cases among non-Africans. If, however, there is extensive periapical infection, sufficient lymphocytes might be chronically present in the jaw marrow so that contact by EBV would be likely when teeth are extracted. This would be the case for people from all regions. Jaw tumors were a presenting 5 ) Geoara~h~_c- .!Liff_ere_n_c~sl manifestation in but 6.6% (38) and 10% (5) of American cases compared to 55% of those in Uganda (9). Among those in all stages of the disease, they were noted in 16.7% in the U.S.A. (5) compared to 76% in Ghana (39). Yet despite high titers of antibody to EBV, only 15% of Iraqi children had jaw involvement (40). This disparity in the association of EBV with jaw tumors suggests that additional factors are required for tumor development. Because the shedding of deciduous teeth is ubiquitous, the geographical differences in jaw tumor prevalence among EBV-positive populations may reflect geographical variations in dental care and the incidence of dental caries due to differences in oral fluoride content of drinking water, etc. hygiene practices, The poor access to dental care of residents of African villages may well be a major contributory factor to their high frequency of jaw tumors. There were no presenting jaw tumors in a Danish series in which EBV antibody was uncommon (411, presumably because Therefore, the infectious agent was absent from the saliva. opening of paths to the interior of the jaws by extensive or the shedding or extraction of teeth could not caries, in Japan, al though EBV favor tumor development. However, antibody is rare and dentistry available, jaw tumors occurred in 91% of the cases and their response to suggesting another etiological chemotherapy was poor (42)) Other differences may exist. For agent for their lymphomas. Indian and Chinese residents of Singapore develop example, EBV infections at dissimilar ages and have different perhaps deciduous teeth antibody titers (43). In addition, are not given proper dental care by certain groups because de-The (44) postulated they are viewed as unimportant. environmental factors being necessary for tumor formation because the oncogenic potential of EBV is rarely realized. Genetics (45) and immune characteristics may provide the required background for the presently discussed dental and hematological factors and may contribute to the geographic differences in jaw tumor development. 6 1 Possible_ relationship _t_o_sa.li.ya_r_y__g.lan_ds.: The belief that the tumors arise in the jawbone (I 1 is not unanimous. Niederman .& a.l (7) stated EBV spread contiguously “from salivary glands to adjacent marrow of the mandible where Lehner oncogenic transformation of lymphocytes occurs.” (18) proposed a neoplastic parotid focus extending along blood vessels and masticatory muscles to the jawbones. However, if tumor arose in the salivary glands, the earliest
335
bony lesions should be along the posterolateral portions of both jaws, areas overlain by the parotid glands (18) and along the inferior border of the mandible where the submandibular and sublingual salivary glands are situated. Yet, the tumor initially involves the opposite surface containing the alveolar processes (1). This disparity suggests that if salivary glands are initially involved, only the parotids are significantly affected and tumor must somehow penetrate extensive soft tissues and bone to reach a specific and distant area of the jaw. The extensive ravages observed at autopsy (7,181 undoubtedly mask the initial changes so the direction of tumor progression cannot be stated retrospectively with confidence. Therefore, primary reliance should be placed on observations made early in the course of the disease (I) rather than terminally. CONCLUSIONS It is hoped that these hypotheses will encourage pathologists to examine otherwise normal accident victims to learn the distribution and cellularity of bone marrow present in the jaws at different ages. Attempts should be made to ascertain the lymphocyte content in the jaws of individuals with infectious mononucleosis and to study the It is locations of early jaw lesions of Burkitt’s lymphoma. important to learn whether there is accompanying salivary gland involvement and whether jaw tumors ever develop before six months of age when the first deciduous teeth erupt and might become carious. If such cases exist, they would indicate that jaw tumors could form in the absence of the postulated dental pathways. Detailed records should be made of the dental status of individuals with Burkitt’s jaw tumors to learn whether the presently postulated chain of events is plausible. It contact frequency typical
is of
believed that the dental pathways that permit EBV with lymphocytes in the jaws explain the of jaw tumors in Burkitt’s lymphoma and the absence of such tumors in non-cranial bones (22).
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