oral pat hology Editor:
CHARLES E. TOMICH, D.D.S., M.S.D. American Academy of Oral Pathology Indiana University School of Dentistry 1121 West Michigan Street Indianapolis, Indiana 46202
Tuberculosis of the tongue A case report with immunologic
study
Takashi Fujibayashi, D.D.S., Ph.D., Yuzo Takahashi, D.D.S., Ph.D., Takanobu Yoneda, D.D.S., Youzo Tagami, D.D.S., Ph.D., and Mikio Kusama, Tokyo) Japan THE
SECOND
DEPARTMENT
OF ORAL
SURGERY,
TOKYO
MEDICAL
AND
DENTAL
D.D.S.,
Ph.D.,
UNIVERSITY
A case of tuberculosis of the tongue in a 59-year-old woman with active pulmonary tuberculosis is described. The lingual tuberculosis was considered to be a secondary infection from the pulmonary disease, but the oral lesions were, in fact, noticed prior to recognition of the pulmonary lesion. This case was marked by a multiplicity of oral lesions arising on the bilateral surfaces of the tongue. Immunologic investigation revealed that cell-mediated immune responses in the patient were within the normal range in terms of the PPD skin test, DNCB skin test, lymphocyte transformation test, and subpopulation of the peripheral blood lymphocytes. Rosette-forming assay on the frozen sections disclosed that T-lymphocytes and macrophages were predominant in the lymphoid cells infiltrating the tuberculous lesion.
T
he incidence of tuberculosis has greatly decreased in well-developed countries throughout the world during the past several decades as a result of the improvement of public health,care and the development of antituberculotic chemotherapy. The most common intraoral lesion of tuberculosis is an ulcer. It may occur both as a primary infection and as a secondary lesion. Primary tuberculous infection of the mouth is very rare but does occur in children and adolescents. The primary lesion is characterized by an indolent painless ulcer associated with enlarged regional lymph nodes. The secondary type usually occurs as an infection from pulmonary tuberculosis at a later age, is usually painful, and has no regional lymph node involvement. The secondary lesions usually are noticed after pulmonary tuberculosis has been determined. The present article concerns a case of secondary tuberculous ulcer occurring on the bilateral surfaces of the tongue. This lesion was actually noticed prior to recognition of the pulmonary tuberculosis. In addition, the results of some investigations of cell-mediated immune responses of the patient are reported.
0030-4220/79/050427+09$00.90/0
0
1979
The C. V. Mosby Co
CASE REPORT
A 59-year-old Japanesewoman was referred to the Deof Oral Surgery, Kawaguchi City Hospital. on May 26, 1976, with a painful ulcer of the tongue.
partment
History
of present
illness
The medical history revealedthat the patient had had bronchial asthmafor 4 yearsbut no diagnosis of pulmonary tuberculosis had been made; nor was there a family history of tuberculosis. During the past several months the patient had experiencedperiodic episodesof a slightly sore tongue which she had attributed to irritation due to either her partial prosthesis or her remaining teeth. Physical
and local examination
Examination revealed a 59-year-old woman in no acute distress. Her general condition was within the normal range, but she did appearto be undernourished. She was 142.5 centimeters tall and weighed 43 kilograms. Oral examination disclosed that the mucous membranes appeared slightly anemic in color. Many teeth had been extracted years before and replaced by a partial prosthesiswhich appearedto be ill fitting. The right lower first premolar and left lower second premolar and second molar teeth had been restored by metal 427
428 Fujihuyuhi
et ul.
Oral Surp. May.
Laboratory
1970
data
Examination of the blood disclosed a red blood cell count of302 x 10’. a hematocrit value of 38 percent. a hemoglobin level of I I .7 Gm./dl., a white blood count of 7,000. and a platelet count of 23.3 x IO’, indicating slight anemia. The erythrocyte sedimentation rate (E.S.R.) was 3.5 mm. In 39 minutes. 75 mm in I hour, and 126 mm. in 3 hours. Liver function. according to berum analysis. \sas normal. Results ol blood chemistry were within a normal range. except for a slight decrease in serum albumin which uas 3.9 Gm.!dl Serologic examination, except for a CRP of 3 - wab wlthin normal limits.
Our lnitml lmpres~~on of the lesion &as that it was a carc~noma, although bilateral lesions are not usual for tongue cancer. A surgical biopsy was perfonned on the ulcerative lesion of the right side of the tongue at the clinic of the Second Department of Oral Surgery. Tokyo Medical and Dental Universit), Hospital. Histopathologic
Fig. 1. Ulceration on right side of tongue. irregularly shaped. surrounded by undermined edge. Fig. 2. Ulceration on left side of tongue. with grayish. ncerotic. granular surface.
ton‘~ue
Bacteriologic
crowns. but these crowns were slightly elongated from the level of the lower partial denture. Necrotic ulcerative lesions were observed on the bilateral surfaces of the tongue. A painful. irregularly shaped ulceration measuring 15 by 5 mm. was located on the right ventral surface in the lateral to anterior margin of the tongue and was surrounded by an undermined edge (Fig. I). The bottom of the ulcer was grayish white in color and appeared necrotic. Palpation revealed tenderness and demonstrated a solid induration within an area of 30 by 15 mm. and a depth of 10 mm. around the ulcer itself. The right lower first premolar touched on the surface of the ulcer in the closed position. A second ulceration on the left ventral surface of the tongue measured 10 by 10 mm. in diameter, with a grayish. necrotic. granular surface (Fig. 2). This lesion was less painful. Palpation showed slight tenderness and dislosed almost no induration around the ulcer. Examination of the submaxillary triangle revealed that the lymph nodes were palpable bilaterally. However, the lymph nodes did not seem enlarged. nor was there any sign of tenderness or fixation to the surrounding tissues. There was no significant lymph node swelling in other parts of the neck.
findings
The specimen consisted of part ot an ulcer and its contigllous submucosal tissue showing a prominent chronic infiammatory change. The ulcerated surfact: was partially covered by a fibrinou:, slough with necrotic polymorphonuclear leukocytes. Beneath the ulcer were tubercles with necrotic central foci surrounded by man! epithelioid cells and a small number of Langhans’ giant cells (Fig. 3). These foci were furthersurrounded b> ;I great number of infiltrating mononuclear lymphoid cells which continued into the lower muscle layer. These tindings uere strongly suggestive of tuberculosis of the examination
Material s~ahbed from the bottom of the ulcer was sent for bacteriologic examination. A direct smear of the material was negative for acid-fast bacilli; however. the culture yielded Mycdxwerirrr~~ mhcrc,lr/o,sis.Therefore. the diagnosis of ELIberculosis of the tongue was confirmed. Roentgenographic
examination
No indication of pulmonary tuberculosis was noticed prior to the biopsy report pointing to tuberculosis of the tongue. The patient was also unaware of the pulmonary infection. Roentgenographic examination of the chest was then perfonned. The radiograph showed coarse pulmonary markings and irregular. mottled shadows of density in the upper half of the right lung tield (Fig. 4). An active tuberculous lesion with a cavitary lesion 3 cm in diameter in the bame field wax confirmed by tomography Further
bacteriologic
examination
The smeal- of the sputum revealed abundant acid-fast bacilli by Ziehl-Neelsen staining (Fig. 5). The number of bacilli was considered to be Grade V by Gaffky’s scale.’ Sensitivity test5 on culture material revealed complete inhibition of grouth at either 70 pgiml. of streptomycin (SM). 1
Fig. 3. Biopsy specimen demonstrating typical features of tuberculous ulceration. Arrow shows a Langhans’ giant cell. (Hemato\ylin and eosin stain. Magnification, X 120.)
pg/ml. of para-amino-salicylic acid (PAS), or 0.1 Fgimi. of isoniazid (INAH). Rifampicin (RFP) also showed complete inhibition at 10 ~g/ml. Final diagnosis
Pulmonary tuberculosis with tuberculous lesions of the tongue was the established diagnosis. Although the tuberculosis of the tongue was determined first, it was most likely that it occurred secondarily to the pulmonary disease. Treatment
and clinical
course
Antituberculosis treatment was started on June 21, 1976, in Saiseikai Kawaguchi Hospital. with oral administration of IO Cm. of PAS. 300 mg. of INAH. and intramuscular injections of I .O Gm. of SM daily. The treatment course is illustrated in Fig 6. The frcqucncy of SM injections was decreased to twice a vvcek on July 21. The patient showed gradual response to the treatment. By August 5. the erythrocyte sedimentation rate had improved to 45 mm. in I hour. and the number of bacilli in a sputum smear had decreased to Grade IV on Gaffky’s scale. The chest radiograph revealed a gradual reduction of the cavitary lesion. and the ulcers of the tongue shoued a rather rapid healing response. On September 2, however. the amount of sputum increased again and the number of bacilli in the sputum again reached Grade V by Gaffky’s scale. In addition, the noted gradual improvement in the useof E.S.R. had become stagnant. On September 17, the treatment plan was changed to oral administration of 400 mg. of INAH 1350 mg 01’RFP daily. and intramuscular injections of 1.O Gm. of enviomycin every other day. The patient responded well. and the ulceration of the tongue had healed completely by the middle of October. Repeated smears and cultures of sputum mere negative for bacilli after November, and repeated chest radiographs exhibited a progression of fibrotic change in the cavitary lesion. E.S.R. was 22 mm. in I
Fig. 4. Roentgenogram of chest showing tuberculous lesion (arrow) in upper half of right lung field.
hour on November 4 and eventually became normal (6 mm.) by Jan. 6, 1977.
IMMUNOLOGIC INVESTIGATION Purpose and methods Tuberculosis has been regarded as one of the infectious diseases in which cell-mediated immunity plays an important part in the defense mechanisms of a host. There is no evidence that humoral antibodies play a part in immunity to tuberculosis. However, little is known concerning the state of cell-mediated immunity of tuberculous patients. In our laboratory a variety of immunologic tests has been performed against oral cancer patients in whom the deficit of cell-mediated immunity has been revealed. Therefore, from an academic view-
Fig. 5. Smearof sputum showing abundantaclcl-tastbacilli (rr~o~\). Grade V by Gaffky’s scale. (LiehI-Neelsen i;tain. Magnitication, x I .OOO.ipoint the patient was subjected to a variety of immunologic studies, including both in vivo and in vitro tests, before treatment was initiated on June 7, although there was no active sign to suspect a deficit in the patient’s cell-mediated immunity. PPD skin test. It is well known that the intradermal injection of specific antigen (PPD) into person suffering from tuberculosis induces a typical delayed hypersensitivity reaction mediated by immunologically competent cells such as T-lymphocytes and macrophages. However, the PPD test cannot be used as an index of resistance to tuberculous infection, because the degree of hypersensitivity. as determined by the cutaneous tuberculin reaction, is not necessarily parallel with that of acquired specific immunity. DNCB skin reaction. The cutaneous reaction to DNCB (2,4-dinitrochlorobenzene) is another test frequently used for evaluating the general ability of patients in cell-mediated immunity. DNCB. a simple chemical reagent, becomes antigenic by binding covalently to cutaneous protein. The antigenic information caught by immunologically competent cells at the cutaneous tissue is brought to the regional lymphat.. ic tissues, where sensitized T-lymphocytes proliferate. The sensitized T-lymphocytes begin to appear in the cutaneous tissue several days later, and they react with specific antigen. The sensitized T-lymphocytes then become activated and release various chemical mediators known as “lymphokines.“ These events result in accumulation of mononuclear cells in the local cutaneous area. The skin reaction shows maximum erythema and induration about 2 weeks after initial application ot DNCB. Therefore, the DNCB skin reaction can evalu-
ate both the afferent and the efferent arcs of the immune response. Two percent (0.5 mg.) of DNCB in 2.5 ~1 of acetone was applied to the skin. The reaction was checked 2 weeks later. Lymnphoc~tt~trunsformation test. The ability of lymphocytes to respond to phytohemagglutinin (PHA) is one of the most frequently used in vitro tests for the general evaluation of cell-mediated immunocompetence. Incubation of lymphocytes with PHA results in their transformation into large blast cells, and this can be assessed by means of incorporation of radioactive DNA precursor into DNA synthesized during the incubation. The actual technique has been described previously.” Subpopulutlon of‘peripheral blood lymphocytes. The subpopulation was assayed by the rosette-forming technique described by Tachibana and Ishikawa.” T-lymphocytes can be identified by their ability to form rosettes with sheep erythrocytes(E) in vitro because of the presence of specific receptors on their surfaces. B-lymphocytes can be distinguished by their receptors for complement and can therefore form rosettes when incubated with E that have reacted with rabbit anti-E IgM antibody and complement (EAC). Most Blymphocytes also have receptors for the Fc portion of immunoglobulin G and can form rosettes by incubating with E treated with anti-E IgG antibody (EA). Rosette-Jbrtning asmy on frozerl tissue sections. The rosette-forming technique used for peripheral blood lymphocytes can be applied for detecting the localization of cells possessing immunologic cell surface markers in frozen tissue sections. E. EAC, and EA were used for indicator cells detecting E-recep-
Volume 47 Number 5
RF P Enviomycin SM
...................................................................................................... Ulllllllnll~lll~lllllil~mn
PAS INAH Gaffkrr
scde
V
IV
IV
521
‘I21
9/5
V
IV
(4
‘O/7
‘l/4
(4
(3
E.S.R. mm/hour j6-:-9117
‘77 ‘/6
Fig. 6. Clinical course of patient illustrating treatment. number of bacilli in sputum by Gaffky’s scale. and erythrocyte sedimentation rate.
tor-bearing cells, complement-receptor-bearing cells, and Fc-receptor-bearing cells, respectively. A part of the biopsied specimen from the right side of the tongue was freshly frozen, and the assay was processed a iubercle. (Hematoxylin and eosin stain. Magnification. ~380.) a, Section layered with E in bright-field illumination. b. Dark-field illumination ot samearea aa a, \howlng adhesion of E to Iymphoid cells around tubercles
patient had an isolated ulcer on each side of the tongue. Although the lesion on the left side of the tongue could not be confirmed by biopsy. it could nevertheless be regarded as a tuberculous ulcer because the lesion persisted for several months and responded to therapq in much the same way as the ulcer on the right side. Brodsky” mentioned four cases of multiple oral lesions out of seven cases of oral tuberculosis. Lagerliif and associates’” also reported a case with an ulceration on the palate and a reddened, swollen lesion on the tongue, both of them showing tuberculous charactcristics by biopsy, which were then confirmed by injecting both tissue specimens into guinea pigs. Darlington and Salmon” classified oral tuberculous lesions into the following three groups: Group 1---tooth
apex and socket cases; Group 2-cases that involve the oral mucous membrane; and Group 3-tuberculosis oi’ the maxilla and mandible. According to Shengold and Sheingold, I7 Group 2 lesions are usually a manifestation of an advanced pulmonary infection; multiple lesions in the mouth occur in this group. All the cases reported by Brodsky” and by Lagerliif and colleagues’” belonged to this group, and the present case can also be considered to be of this type. The intraoral sites of tuberculosis reported in the literature which we have collected have been summarized in Table II. The frequent sites were tooth socket. tongue, gingiva. lip. and palate. Primary oral tuberculous lesions’X~~Z’were found in gingiva, tooth socket. and buccal fold. On the other hand, tongue. palate, and
Volume 41 Number S
Tuberculosis
of tongue 433
Fig. 7 (Cont’d). c, Section layered with EA showing adhesion of EA to peritubercular area. Dark-field illumination. d, Section layered with EAC showing only scattered adhesion. Dark-field illumination.
lip were reported to be frequent sites for secondary oral tuberculous lesions.“, 13-17,22-3oShengold and Sheingold” reported twenty cases of secondary oral tuberculosis, and nine of them involved the tooth apex and socket. They assumed that all but one of the nine cases were infected from positive sputum through an exogenous route. Many arguments have been presented concerning the route of infection to the oral cavity from pulmonary lesions. According to Brodsky,14 many intraoral surgical procedures, such as tooth extraction, apicotomy, and removal of cysts, were undertaken in tuberculosis patients with high Gaffky counts in the sputum, but postoperative tuberculous infections resulting therefrom in the mouth were extremely rare. Shengold and Sheingoldt7 mentioned that trauma from dental ex-
tractions and other oral procedures rarely was followed by autoinoculations, and they also pointed out that some patients who have negative sputum nevertheless may develop oral lesions. These findings seem to favor the concept that oral tuberculous lesions result most frequently from a hematogenous infection. Another report3’ indicates that tuberculous infection of periapical areas and tooth sockets following extraction has been seen in about 8 percent of persons with long-standing pulmonary tuberculosis. Even this rate of incidence can probably be ascribed to hematogenous infection, because injured or inflamed tissue tends to localize blood-borne bacteria. 23 However, the role of trauma should not be underestimated, as the stratified squamous epithelium of the oral cavity probably resists the direct penetration of tubercle bacilli. lo The bacilli were
434
Fyjibuyashi
et ul
Oral Surg May. 1979
Table II. Intraoral sites Yew Primm-y owl ruhrrculovis Boyes et al.‘” Browne’” Gardner and Hanft”’ O’Neil” Swonddr\- ortrl tuhef-culosi.\ CoIlin\ and Cook”’ Brod\ky” Wolfer et ;II.~~ Shengold and Shemgold” Brucexz’ Thilander and Wenmtriimz4 Radden ‘,md Re,lde’” ‘ Lazerliif et al. I6 Brennan and Urabec” Pratap et al, 1’ Harri\ et ‘,II.~~ R,lrnul,l ‘ L et L,I! x Bhatt and Dholakia”” De I.athouuer et al.2(’ Sachs and Ei
CHARLES E. TOMICH, D.D.S., M.S.D. American Academy of Oral Pathology Indiana University School of Dentistry 1121 West Michigan Street Indianapolis, Indiana 46202
Tuberculosis of the tongue A case report with immunologic
study
Takashi Fujibayashi, D.D.S., Ph.D., Yuzo Takahashi, D.D.S., Ph.D., Takanobu Yoneda, D.D.S., Youzo Tagami, D.D.S., Ph.D., and Mikio Kusama, Tokyo) Japan THE
SECOND
DEPARTMENT
OF ORAL
SURGERY,
TOKYO
MEDICAL
AND
DENTAL
D.D.S.,
Ph.D.,
UNIVERSITY
A case of tuberculosis of the tongue in a 59-year-old woman with active pulmonary tuberculosis is described. The lingual tuberculosis was considered to be a secondary infection from the pulmonary disease, but the oral lesions were, in fact, noticed prior to recognition of the pulmonary lesion. This case was marked by a multiplicity of oral lesions arising on the bilateral surfaces of the tongue. Immunologic investigation revealed that cell-mediated immune responses in the patient were within the normal range in terms of the PPD skin test, DNCB skin test, lymphocyte transformation test, and subpopulation of the peripheral blood lymphocytes. Rosette-forming assay on the frozen sections disclosed that T-lymphocytes and macrophages were predominant in the lymphoid cells infiltrating the tuberculous lesion.
T
he incidence of tuberculosis has greatly decreased in well-developed countries throughout the world during the past several decades as a result of the improvement of public health,care and the development of antituberculotic chemotherapy. The most common intraoral lesion of tuberculosis is an ulcer. It may occur both as a primary infection and as a secondary lesion. Primary tuberculous infection of the mouth is very rare but does occur in children and adolescents. The primary lesion is characterized by an indolent painless ulcer associated with enlarged regional lymph nodes. The secondary type usually occurs as an infection from pulmonary tuberculosis at a later age, is usually painful, and has no regional lymph node involvement. The secondary lesions usually are noticed after pulmonary tuberculosis has been determined. The present article concerns a case of secondary tuberculous ulcer occurring on the bilateral surfaces of the tongue. This lesion was actually noticed prior to recognition of the pulmonary tuberculosis. In addition, the results of some investigations of cell-mediated immune responses of the patient are reported.
0030-4220/79/050427+09$00.90/0
0
1979
The C. V. Mosby Co
CASE REPORT
A 59-year-old Japanesewoman was referred to the Deof Oral Surgery, Kawaguchi City Hospital. on May 26, 1976, with a painful ulcer of the tongue.
partment
History
of present
illness
The medical history revealedthat the patient had had bronchial asthmafor 4 yearsbut no diagnosis of pulmonary tuberculosis had been made; nor was there a family history of tuberculosis. During the past several months the patient had experiencedperiodic episodesof a slightly sore tongue which she had attributed to irritation due to either her partial prosthesis or her remaining teeth. Physical
and local examination
Examination revealed a 59-year-old woman in no acute distress. Her general condition was within the normal range, but she did appearto be undernourished. She was 142.5 centimeters tall and weighed 43 kilograms. Oral examination disclosed that the mucous membranes appeared slightly anemic in color. Many teeth had been extracted years before and replaced by a partial prosthesiswhich appearedto be ill fitting. The right lower first premolar and left lower second premolar and second molar teeth had been restored by metal 427
428 Fujihuyuhi
et ul.
Oral Surp. May.
Laboratory
1970
data
Examination of the blood disclosed a red blood cell count of302 x 10’. a hematocrit value of 38 percent. a hemoglobin level of I I .7 Gm./dl., a white blood count of 7,000. and a platelet count of 23.3 x IO’, indicating slight anemia. The erythrocyte sedimentation rate (E.S.R.) was 3.5 mm. In 39 minutes. 75 mm in I hour, and 126 mm. in 3 hours. Liver function. according to berum analysis. \sas normal. Results ol blood chemistry were within a normal range. except for a slight decrease in serum albumin which uas 3.9 Gm.!dl Serologic examination, except for a CRP of 3 - wab wlthin normal limits.
Our lnitml lmpres~~on of the lesion &as that it was a carc~noma, although bilateral lesions are not usual for tongue cancer. A surgical biopsy was perfonned on the ulcerative lesion of the right side of the tongue at the clinic of the Second Department of Oral Surgery. Tokyo Medical and Dental Universit), Hospital. Histopathologic
Fig. 1. Ulceration on right side of tongue. irregularly shaped. surrounded by undermined edge. Fig. 2. Ulceration on left side of tongue. with grayish. ncerotic. granular surface.
ton‘~ue
Bacteriologic
crowns. but these crowns were slightly elongated from the level of the lower partial denture. Necrotic ulcerative lesions were observed on the bilateral surfaces of the tongue. A painful. irregularly shaped ulceration measuring 15 by 5 mm. was located on the right ventral surface in the lateral to anterior margin of the tongue and was surrounded by an undermined edge (Fig. I). The bottom of the ulcer was grayish white in color and appeared necrotic. Palpation revealed tenderness and demonstrated a solid induration within an area of 30 by 15 mm. and a depth of 10 mm. around the ulcer itself. The right lower first premolar touched on the surface of the ulcer in the closed position. A second ulceration on the left ventral surface of the tongue measured 10 by 10 mm. in diameter, with a grayish. necrotic. granular surface (Fig. 2). This lesion was less painful. Palpation showed slight tenderness and dislosed almost no induration around the ulcer. Examination of the submaxillary triangle revealed that the lymph nodes were palpable bilaterally. However, the lymph nodes did not seem enlarged. nor was there any sign of tenderness or fixation to the surrounding tissues. There was no significant lymph node swelling in other parts of the neck.
findings
The specimen consisted of part ot an ulcer and its contigllous submucosal tissue showing a prominent chronic infiammatory change. The ulcerated surfact: was partially covered by a fibrinou:, slough with necrotic polymorphonuclear leukocytes. Beneath the ulcer were tubercles with necrotic central foci surrounded by man! epithelioid cells and a small number of Langhans’ giant cells (Fig. 3). These foci were furthersurrounded b> ;I great number of infiltrating mononuclear lymphoid cells which continued into the lower muscle layer. These tindings uere strongly suggestive of tuberculosis of the examination
Material s~ahbed from the bottom of the ulcer was sent for bacteriologic examination. A direct smear of the material was negative for acid-fast bacilli; however. the culture yielded Mycdxwerirrr~~ mhcrc,lr/o,sis.Therefore. the diagnosis of ELIberculosis of the tongue was confirmed. Roentgenographic
examination
No indication of pulmonary tuberculosis was noticed prior to the biopsy report pointing to tuberculosis of the tongue. The patient was also unaware of the pulmonary infection. Roentgenographic examination of the chest was then perfonned. The radiograph showed coarse pulmonary markings and irregular. mottled shadows of density in the upper half of the right lung tield (Fig. 4). An active tuberculous lesion with a cavitary lesion 3 cm in diameter in the bame field wax confirmed by tomography Further
bacteriologic
examination
The smeal- of the sputum revealed abundant acid-fast bacilli by Ziehl-Neelsen staining (Fig. 5). The number of bacilli was considered to be Grade V by Gaffky’s scale.’ Sensitivity test5 on culture material revealed complete inhibition of grouth at either 70 pgiml. of streptomycin (SM). 1
Fig. 3. Biopsy specimen demonstrating typical features of tuberculous ulceration. Arrow shows a Langhans’ giant cell. (Hemato\ylin and eosin stain. Magnification, X 120.)
pg/ml. of para-amino-salicylic acid (PAS), or 0.1 Fgimi. of isoniazid (INAH). Rifampicin (RFP) also showed complete inhibition at 10 ~g/ml. Final diagnosis
Pulmonary tuberculosis with tuberculous lesions of the tongue was the established diagnosis. Although the tuberculosis of the tongue was determined first, it was most likely that it occurred secondarily to the pulmonary disease. Treatment
and clinical
course
Antituberculosis treatment was started on June 21, 1976, in Saiseikai Kawaguchi Hospital. with oral administration of IO Cm. of PAS. 300 mg. of INAH. and intramuscular injections of I .O Gm. of SM daily. The treatment course is illustrated in Fig 6. The frcqucncy of SM injections was decreased to twice a vvcek on July 21. The patient showed gradual response to the treatment. By August 5. the erythrocyte sedimentation rate had improved to 45 mm. in I hour. and the number of bacilli in a sputum smear had decreased to Grade IV on Gaffky’s scale. The chest radiograph revealed a gradual reduction of the cavitary lesion. and the ulcers of the tongue shoued a rather rapid healing response. On September 2, however. the amount of sputum increased again and the number of bacilli in the sputum again reached Grade V by Gaffky’s scale. In addition, the noted gradual improvement in the useof E.S.R. had become stagnant. On September 17, the treatment plan was changed to oral administration of 400 mg. of INAH 1350 mg 01’RFP daily. and intramuscular injections of 1.O Gm. of enviomycin every other day. The patient responded well. and the ulceration of the tongue had healed completely by the middle of October. Repeated smears and cultures of sputum mere negative for bacilli after November, and repeated chest radiographs exhibited a progression of fibrotic change in the cavitary lesion. E.S.R. was 22 mm. in I
Fig. 4. Roentgenogram of chest showing tuberculous lesion (arrow) in upper half of right lung field.
hour on November 4 and eventually became normal (6 mm.) by Jan. 6, 1977.
IMMUNOLOGIC INVESTIGATION Purpose and methods Tuberculosis has been regarded as one of the infectious diseases in which cell-mediated immunity plays an important part in the defense mechanisms of a host. There is no evidence that humoral antibodies play a part in immunity to tuberculosis. However, little is known concerning the state of cell-mediated immunity of tuberculous patients. In our laboratory a variety of immunologic tests has been performed against oral cancer patients in whom the deficit of cell-mediated immunity has been revealed. Therefore, from an academic view-
Fig. 5. Smearof sputum showing abundantaclcl-tastbacilli (rr~o~\). Grade V by Gaffky’s scale. (LiehI-Neelsen i;tain. Magnitication, x I .OOO.ipoint the patient was subjected to a variety of immunologic studies, including both in vivo and in vitro tests, before treatment was initiated on June 7, although there was no active sign to suspect a deficit in the patient’s cell-mediated immunity. PPD skin test. It is well known that the intradermal injection of specific antigen (PPD) into person suffering from tuberculosis induces a typical delayed hypersensitivity reaction mediated by immunologically competent cells such as T-lymphocytes and macrophages. However, the PPD test cannot be used as an index of resistance to tuberculous infection, because the degree of hypersensitivity. as determined by the cutaneous tuberculin reaction, is not necessarily parallel with that of acquired specific immunity. DNCB skin reaction. The cutaneous reaction to DNCB (2,4-dinitrochlorobenzene) is another test frequently used for evaluating the general ability of patients in cell-mediated immunity. DNCB. a simple chemical reagent, becomes antigenic by binding covalently to cutaneous protein. The antigenic information caught by immunologically competent cells at the cutaneous tissue is brought to the regional lymphat.. ic tissues, where sensitized T-lymphocytes proliferate. The sensitized T-lymphocytes begin to appear in the cutaneous tissue several days later, and they react with specific antigen. The sensitized T-lymphocytes then become activated and release various chemical mediators known as “lymphokines.“ These events result in accumulation of mononuclear cells in the local cutaneous area. The skin reaction shows maximum erythema and induration about 2 weeks after initial application ot DNCB. Therefore, the DNCB skin reaction can evalu-
ate both the afferent and the efferent arcs of the immune response. Two percent (0.5 mg.) of DNCB in 2.5 ~1 of acetone was applied to the skin. The reaction was checked 2 weeks later. Lymnphoc~tt~trunsformation test. The ability of lymphocytes to respond to phytohemagglutinin (PHA) is one of the most frequently used in vitro tests for the general evaluation of cell-mediated immunocompetence. Incubation of lymphocytes with PHA results in their transformation into large blast cells, and this can be assessed by means of incorporation of radioactive DNA precursor into DNA synthesized during the incubation. The actual technique has been described previously.” Subpopulutlon of‘peripheral blood lymphocytes. The subpopulation was assayed by the rosette-forming technique described by Tachibana and Ishikawa.” T-lymphocytes can be identified by their ability to form rosettes with sheep erythrocytes(E) in vitro because of the presence of specific receptors on their surfaces. B-lymphocytes can be distinguished by their receptors for complement and can therefore form rosettes when incubated with E that have reacted with rabbit anti-E IgM antibody and complement (EAC). Most Blymphocytes also have receptors for the Fc portion of immunoglobulin G and can form rosettes by incubating with E treated with anti-E IgG antibody (EA). Rosette-Jbrtning asmy on frozerl tissue sections. The rosette-forming technique used for peripheral blood lymphocytes can be applied for detecting the localization of cells possessing immunologic cell surface markers in frozen tissue sections. E. EAC, and EA were used for indicator cells detecting E-recep-
Volume 47 Number 5
RF P Enviomycin SM
...................................................................................................... Ulllllllnll~lll~lllllil~mn
PAS INAH Gaffkrr
scde
V
IV
IV
521
‘I21
9/5
V
IV
(4
‘O/7
‘l/4
(4
(3
E.S.R. mm/hour j6-:-9117
‘77 ‘/6
Fig. 6. Clinical course of patient illustrating treatment. number of bacilli in sputum by Gaffky’s scale. and erythrocyte sedimentation rate.
tor-bearing cells, complement-receptor-bearing cells, and Fc-receptor-bearing cells, respectively. A part of the biopsied specimen from the right side of the tongue was freshly frozen, and the assay was processed a iubercle. (Hematoxylin and eosin stain. Magnification. ~380.) a, Section layered with E in bright-field illumination. b. Dark-field illumination ot samearea aa a, \howlng adhesion of E to Iymphoid cells around tubercles
patient had an isolated ulcer on each side of the tongue. Although the lesion on the left side of the tongue could not be confirmed by biopsy. it could nevertheless be regarded as a tuberculous ulcer because the lesion persisted for several months and responded to therapq in much the same way as the ulcer on the right side. Brodsky” mentioned four cases of multiple oral lesions out of seven cases of oral tuberculosis. Lagerliif and associates’” also reported a case with an ulceration on the palate and a reddened, swollen lesion on the tongue, both of them showing tuberculous charactcristics by biopsy, which were then confirmed by injecting both tissue specimens into guinea pigs. Darlington and Salmon” classified oral tuberculous lesions into the following three groups: Group 1---tooth
apex and socket cases; Group 2-cases that involve the oral mucous membrane; and Group 3-tuberculosis oi’ the maxilla and mandible. According to Shengold and Sheingold, I7 Group 2 lesions are usually a manifestation of an advanced pulmonary infection; multiple lesions in the mouth occur in this group. All the cases reported by Brodsky” and by Lagerliif and colleagues’” belonged to this group, and the present case can also be considered to be of this type. The intraoral sites of tuberculosis reported in the literature which we have collected have been summarized in Table II. The frequent sites were tooth socket. tongue, gingiva. lip. and palate. Primary oral tuberculous lesions’X~~Z’were found in gingiva, tooth socket. and buccal fold. On the other hand, tongue. palate, and
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Tuberculosis
of tongue 433
Fig. 7 (Cont’d). c, Section layered with EA showing adhesion of EA to peritubercular area. Dark-field illumination. d, Section layered with EAC showing only scattered adhesion. Dark-field illumination.
lip were reported to be frequent sites for secondary oral tuberculous lesions.“, 13-17,22-3oShengold and Sheingold” reported twenty cases of secondary oral tuberculosis, and nine of them involved the tooth apex and socket. They assumed that all but one of the nine cases were infected from positive sputum through an exogenous route. Many arguments have been presented concerning the route of infection to the oral cavity from pulmonary lesions. According to Brodsky,14 many intraoral surgical procedures, such as tooth extraction, apicotomy, and removal of cysts, were undertaken in tuberculosis patients with high Gaffky counts in the sputum, but postoperative tuberculous infections resulting therefrom in the mouth were extremely rare. Shengold and Sheingoldt7 mentioned that trauma from dental ex-
tractions and other oral procedures rarely was followed by autoinoculations, and they also pointed out that some patients who have negative sputum nevertheless may develop oral lesions. These findings seem to favor the concept that oral tuberculous lesions result most frequently from a hematogenous infection. Another report3’ indicates that tuberculous infection of periapical areas and tooth sockets following extraction has been seen in about 8 percent of persons with long-standing pulmonary tuberculosis. Even this rate of incidence can probably be ascribed to hematogenous infection, because injured or inflamed tissue tends to localize blood-borne bacteria. 23 However, the role of trauma should not be underestimated, as the stratified squamous epithelium of the oral cavity probably resists the direct penetration of tubercle bacilli. lo The bacilli were
434
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Oral Surg May. 1979
Table II. Intraoral sites Yew Primm-y owl ruhrrculovis Boyes et al.‘” Browne’” Gardner and Hanft”’ O’Neil” Swonddr\- ortrl tuhef-culosi.\ CoIlin\ and Cook”’ Brod\ky” Wolfer et ;II.~~ Shengold and Shemgold” Brucexz’ Thilander and Wenmtriimz4 Radden ‘,md Re,lde’” ‘ Lazerliif et al. I6 Brennan and Urabec” Pratap et al, 1’ Harri\ et ‘,II.~~ R,lrnul,l ‘ L et L,I! x Bhatt and Dholakia”” De I.athouuer et al.2(’ Sachs and Ei
