- Email: [email protected]
Relapse of acute lymphoblastic leukemia in the jaw
Relapse of acute lymphoblastic leukemia in the jaw Abdulaziz A. Bakathir, BDS, MFDS RCSEd, MSc, MOralSurg, RCSEd,a and Aisha S. Al-Hamdani, MD, FRCPath,b Muscat, Oman SULTAN QABOOS UNIVERSITY HOSPITAL, SULTAN QABOOS UNIVERSITY
This case report describes the clinical case of relapse of precursor B-cell acute lymphoblastic leukemia in the jaw of a 19-year-old female patient who presented with facial swelling, sensory disturbances of the face, and teeth mobility 10 months after a successful allogenic bone marrow transplant. The oral and dental presentations were the only features indicating leukemic relapse in this patient. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 107:e14-e16)
Allogenic bone marrow transplant (BMT) is now considered to be part of the treatment algorithm for patients with acute lymphoblastic leukemia (ALL).1 Recently, an increase in the incidence of extramedullary (EM) relapse of ALL has been reported after BMT, with brain and testis being the most commonly involved sites.2,3 Extramedullary relapse of acute leukemias can present with or without bone marrow involvement.4-6 Relapse of leukemia presenting in the jaw bones is extremely rare. We are aware of a few cases reported in the English-language literature to date, with leukemic jaw relapse being reported more in children than in adults.1,4,7,8 The present case report describes a clinical case of a 19-year-old female patient presenting with facial swelling, facial sensory nerve disturbances, and teeth mobility that were the first indication of leukemic relapse in the jaw 10 months after allogenic BMT. CASE REPORT A 15-year-old Omani female patient who was diagnosed in December 2000 with precursor B-cell acute lymphoblastic leukemia, received a treatment regime devised by the Medical Research Council U.K. protocol. This involved chemotherapy and cranial irradiation followed by intermittent maintenance therapy. In December 2002, the patient’s leukemic status relapsed, and she was restarted on 5 cycles of chemotherapy to be followed by BMT. After chemotherapy, the patient remained in remission and in May 2003 she had a successful allogenic BMT from an HLA-matched sister. Almost 10 months after BMT, at the age of 19 years, she was referred to the Oral Health Department at Sultan Qaboos
University Hospital with a chief complaint of facial swelling and altered sensation affecting the left side of the lower lip and chin. She reported that the swelling and numbness had been there for almost 1 week, with no reported history of trauma. Clinical examination showed an afebrile and fully conscious patient with mild swelling affecting the right infraorbital region and left side of the lower jaw. There was bilateral palpable and tender submandibular lymphadenopathy. Assessment of the sensory nerves of the face revealed paresthesia of the right infraorbital nerve and anesthesia of the left mental nerve. Intraoral examination demonstrated a tender buccal swelling in the upper right canine and premolar region and in the lower left first molar region, with an associated grade III mobility of teeth numbers 5, 6, and 19. Radiographic examination using an orthopantomograph (OPG) revealed areas of ill-defined radiolucency apical to teeth numbers 5, 6, 19, and 20. There was no radiographic evidence of any root resorption, but there was a loss of the inferior dental canal lines bilaterally (Fig. 1). A biopsy of the upper right maxillary canine and premolar and the lower left molar region was conducted under local anesthesia with extraction of the associated mobile teeth. At the time of biopsy, the area of swelling revealed a white, waxy, avascular tissue in the apical and buccal aspect. Microscopic examination of the biopsies from the maxilla and mandible showed similar histopathologic appearances. Both
a
Consultant, Oral and Maxillofacial Surgeon, Oral Health Department. b Consultant, Department of Pathology. Received for publication Dec 27, 2008; returned for revision Jan 21, 2009; accepted for publication Jan 21, 2009. 1079-2104/$ - see front matter © 2009 Published by Mosby, Inc. doi:10.1016/j.tripleo.2009.01.029
e14
Fig. 1. Orthopantomogram showing loss of inferior dental canal lines bilaterally and areas of ill-defined radiolucency apical to teeth numbers 5, 6, 19, and 20.
OOOOE Volume 107, Number 5
Bakathir and Al-Hamdani e15
Fig. 2. A, Photomicrograph from the mandible showing trabeculae of bone widely separated by medium-size blast cells (hematoxylin-eosin stain, ⫻10 magnification). B, Positive immunohistochemistry stain for CD10. C, Positive cytoplasmic staining for B-cell marker (CD79a). D, Strong nuclear staining for terminal deoxynucleotidyl transferase (TdT).
demonstrated trabeculae of bone widely separated by a dense monomorphous infiltrate consisting of medium-sized blasts with round to oval and indented nuclei having delicate nuclear chromatin, scant cytoplasm, and inconspicuous nucleoli. Immunohistochemistry studies showed a strong positive staining for CD10, CD79a, and TdT, confirming the diagnosis of relapse precursor B-cell ALL (Fig. 2). The morphology and the immunohistochemical profiles of the leukemic infiltrate in the maxillary and mandibular tissues were identical to the leukemic infiltrate seen in the first bone marrow (BM) trephine biopsy where the initial diagnosis of precursor B-cell ALL was made. After our diagnosis of relapse of ALL, the patient underwent a repeat BM trephine biopsy, which also demonstrated BM relapse of ALL with the morphology and immunohistochemical profiles similar to those seen in the oral and pre-BMT biopsies.
DISCUSSION Relapse of acute leukemias can affect the BM, EM sites, or both. The frequency of extramedullary relapse
of ALL after BMT varies widely in the literature, with reported rates of 30%-50% after allogenic BMT.1,3,6 Extramedullary relapse tends to occur later than BM relapse, with the risk period for EM relapse in ALL appearing to be within 2 years after transplant.1,9,10 In EM relapse, there appears to be a predilection for acute leukemias to relapse in soft tissue and to continue to relapse in soft tissues more often than bone.6,9 The brain and the testis are the most commonly reported soft tissue sites, and relapse to other locations is exceedingly rare.1,3,9 There are single reports on relapse affecting abdominal lymph nodes, bones including the jaw, mediastinum, orbit, gingival tissue, kidney, heart, and breast.1,9 When acute leukemia relapse occurs after allogeneic BMT, the disease is often more resistant to treatment, with generally poor prognosis. Most published studies report a median post-relapse survival time of about 8
e16
OOOOE May 2009
Bakathir and Al-Hamdani
months.1,10 This was the case in the present patient, who died 6 months after the diagnosis of the jaw relapse, owing to refractory disease. Many reported cases of ALL relapse in EM sites show that the relapse was often the first sign indicating relapse of leukemia, with or without simultaneous BM relapse.7-9 This was the finding in the present case, where the dental presentation in the jaw was the only indication for relapse of ALL in this patient. Oral complications occur frequently in leukemia and may be the presenting feature of the disease. Oral manifestations usually arise from an underlying thrombocytopenia, neutropenia, or impaired granulocyte function, or they may result from direct leukemic infiltration.11 Earlier reports have described a number of leukemic-induced oral changes, including pain, gingival swelling, bleeding, ulceration, bony changes, and infection. However, the oral manifestations specifically associated with relapse of ALL have been infrequently documented in the literature.5,7,8,11-13 Published case reports show that the features of oral relapse in ALL include numbness of the lip and chin, gingival tissue enlargement, jaw pain, and swelling.2,5,8,12,13 Relapse of leukemia presenting in the jaw is extremely rare. We are aware of a few isolated cases reported, with relapse being more commonly seen in children than in adults.1,4,7-9,13 This could be attributed to the existence of myelopoiesis in the jaw until after puberty, making it a potential site for leukemic infiltration and relapse, especially in the lower jaw.5,7,14 Jaw involvement in leukemia was first described in 1944.7 In 1971, Curtis,14 in his review of panoramic radiographs of 214 children with leukemias, demonstrated the dental and jaw abnormalities of patients with relapsed ALL on panoramic radiographs. These radiographic abnormalities varied in severity from obvious destruction of the dental crypts and lamina dura or displacement of teeth to more subtle changes in radiodensity of jaw and loss of the inferior dental canal lines. In the present case, the OPG clearly showed areas of ill-defined radiolucency in the maxillary and mandibular alveolar bone areas and the disappearance of the inferior dental canal lines bilaterally. In conclusion, the authors hope that this report serves as a reminder to those, particularly dentists, caring for survivors of leukemia, to be vigilant regarding complaints of jaw pain, swelling, or numbness. Although these symptoms may be of dental origin or the result of a side effect of chemotherapeutic treatment, they may
also be an important sign indicating the relapse of leukemia. In addition, the authors strongly stress the importance of regular dental reviews on these patients, even when in remission, and ideally in a specialist center, as part of their continuing multidisciplinary care. REFERENCES 1. Lee KH, Lee JH, Choi SJ, Lee JH, Kim S, Seol M, et al. Bone marrow vs extramedullary relapse of acute leukemia after allogeneic hematopoietic cell transplantation: risk factors and clinical course. Bone Marrow Transplant 2003;32:835-42. 2. Au WY, Wong KY, Leung RYY, Tong ACK. Isolated gingival relapse of acute lymphoblastic leukemia after transplantation. J Oral Pathol Med 2008;37:249-51. 3. Lee KH, Lee JH, Kim S, Lee JS, Kim SH, Kim WK. High frequency of extramedullary relapse of acute leukemia after allogeneic bone marrow transplantation. Bone Marrow Transplant 2000;26:147-52. 4. Benson RE, Rodd HD, North S, Loescher AR, Farthing PM, Payne M. Leukaemic infiltration of the mandible in a young girl. Int J Paediatr Dent 2007;17:145-50. 5. Huffman GG. Mandibular involvement in acute lymphocytic leukemia: report of a case. J Oral Surg 1976;34:842-5. 6. Nomura K, Okamoto T, Nakao M, Ueda K, Akano Y, Fujita Y, et al. Multiple bone lesions after allogeneic bone marrow transplantation in a patient with relapsed adult acute lymphoblastic leukemia: minimal residual disease analysis may predict extramedullary relapse. Leuk Lymphoma 2001;42:1305-8. 7. Williams SA, Duggan MB, Bailey CC. Jaw involvement in acute lymphoblastic leukaemia. Br Dent J 1983;155:164-6. 8. Hiraki A, Nakamura S, Abe K, Takenoshita Y, Horinouchi Y, Shinohara M, et al. Numb chin syndrome as an initial symptom of acute lymphocytic leukemia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;83:555-61. 9. Cunningham I. Extramedullary sites of leukemia relapse after transplant. Leuk Lymphoma 2006;47:1754-67. 10. Al Lamki Z, Wali YA, Shah WM, Zachariah M. Relapsed acute leukemia in children: Oman experience. Pediatr Hematol Oncol 2004;21:167-73. 11. Cousin GCS. Oral manifestations of leukaemia. Dent Update 1997;24:67-70. 12. Stafford R, Sonis S, Lockhart P, Sonis A. Oral pathoses as diagnostic indication in leukaemia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1980;50:134-9. 13. Bernstein ML, Schwartz S. Mandibular relapse in acute leukemia. Am J Pediatr Oncol 1986;8:240-4. 14. Curtis AB. Childhood leukemias: osseous changes in jaws on panoramic dental radiographs. J Am Dent Assoc 1971;83:844-7. Reprint requests: Abdulaziz A. Bakathir Oral Health Department Sultan Qaboos University Hospital Sultan Qaboos University P.O. Box 38, PC 123, Sultanate of Oman [email protected]
This case report describes the clinical case of relapse of precursor B-cell acute lymphoblastic leukemia in the jaw of a 19-year-old female patient who presented with facial swelling, sensory disturbances of the face, and teeth mobility 10 months after a successful allogenic bone marrow transplant. The oral and dental presentations were the only features indicating leukemic relapse in this patient. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 107:e14-e16)
Allogenic bone marrow transplant (BMT) is now considered to be part of the treatment algorithm for patients with acute lymphoblastic leukemia (ALL).1 Recently, an increase in the incidence of extramedullary (EM) relapse of ALL has been reported after BMT, with brain and testis being the most commonly involved sites.2,3 Extramedullary relapse of acute leukemias can present with or without bone marrow involvement.4-6 Relapse of leukemia presenting in the jaw bones is extremely rare. We are aware of a few cases reported in the English-language literature to date, with leukemic jaw relapse being reported more in children than in adults.1,4,7,8 The present case report describes a clinical case of a 19-year-old female patient presenting with facial swelling, facial sensory nerve disturbances, and teeth mobility that were the first indication of leukemic relapse in the jaw 10 months after allogenic BMT. CASE REPORT A 15-year-old Omani female patient who was diagnosed in December 2000 with precursor B-cell acute lymphoblastic leukemia, received a treatment regime devised by the Medical Research Council U.K. protocol. This involved chemotherapy and cranial irradiation followed by intermittent maintenance therapy. In December 2002, the patient’s leukemic status relapsed, and she was restarted on 5 cycles of chemotherapy to be followed by BMT. After chemotherapy, the patient remained in remission and in May 2003 she had a successful allogenic BMT from an HLA-matched sister. Almost 10 months after BMT, at the age of 19 years, she was referred to the Oral Health Department at Sultan Qaboos
University Hospital with a chief complaint of facial swelling and altered sensation affecting the left side of the lower lip and chin. She reported that the swelling and numbness had been there for almost 1 week, with no reported history of trauma. Clinical examination showed an afebrile and fully conscious patient with mild swelling affecting the right infraorbital region and left side of the lower jaw. There was bilateral palpable and tender submandibular lymphadenopathy. Assessment of the sensory nerves of the face revealed paresthesia of the right infraorbital nerve and anesthesia of the left mental nerve. Intraoral examination demonstrated a tender buccal swelling in the upper right canine and premolar region and in the lower left first molar region, with an associated grade III mobility of teeth numbers 5, 6, and 19. Radiographic examination using an orthopantomograph (OPG) revealed areas of ill-defined radiolucency apical to teeth numbers 5, 6, 19, and 20. There was no radiographic evidence of any root resorption, but there was a loss of the inferior dental canal lines bilaterally (Fig. 1). A biopsy of the upper right maxillary canine and premolar and the lower left molar region was conducted under local anesthesia with extraction of the associated mobile teeth. At the time of biopsy, the area of swelling revealed a white, waxy, avascular tissue in the apical and buccal aspect. Microscopic examination of the biopsies from the maxilla and mandible showed similar histopathologic appearances. Both
a
Consultant, Oral and Maxillofacial Surgeon, Oral Health Department. b Consultant, Department of Pathology. Received for publication Dec 27, 2008; returned for revision Jan 21, 2009; accepted for publication Jan 21, 2009. 1079-2104/$ - see front matter © 2009 Published by Mosby, Inc. doi:10.1016/j.tripleo.2009.01.029
e14
Fig. 1. Orthopantomogram showing loss of inferior dental canal lines bilaterally and areas of ill-defined radiolucency apical to teeth numbers 5, 6, 19, and 20.
OOOOE Volume 107, Number 5
Bakathir and Al-Hamdani e15
Fig. 2. A, Photomicrograph from the mandible showing trabeculae of bone widely separated by medium-size blast cells (hematoxylin-eosin stain, ⫻10 magnification). B, Positive immunohistochemistry stain for CD10. C, Positive cytoplasmic staining for B-cell marker (CD79a). D, Strong nuclear staining for terminal deoxynucleotidyl transferase (TdT).
demonstrated trabeculae of bone widely separated by a dense monomorphous infiltrate consisting of medium-sized blasts with round to oval and indented nuclei having delicate nuclear chromatin, scant cytoplasm, and inconspicuous nucleoli. Immunohistochemistry studies showed a strong positive staining for CD10, CD79a, and TdT, confirming the diagnosis of relapse precursor B-cell ALL (Fig. 2). The morphology and the immunohistochemical profiles of the leukemic infiltrate in the maxillary and mandibular tissues were identical to the leukemic infiltrate seen in the first bone marrow (BM) trephine biopsy where the initial diagnosis of precursor B-cell ALL was made. After our diagnosis of relapse of ALL, the patient underwent a repeat BM trephine biopsy, which also demonstrated BM relapse of ALL with the morphology and immunohistochemical profiles similar to those seen in the oral and pre-BMT biopsies.
DISCUSSION Relapse of acute leukemias can affect the BM, EM sites, or both. The frequency of extramedullary relapse
of ALL after BMT varies widely in the literature, with reported rates of 30%-50% after allogenic BMT.1,3,6 Extramedullary relapse tends to occur later than BM relapse, with the risk period for EM relapse in ALL appearing to be within 2 years after transplant.1,9,10 In EM relapse, there appears to be a predilection for acute leukemias to relapse in soft tissue and to continue to relapse in soft tissues more often than bone.6,9 The brain and the testis are the most commonly reported soft tissue sites, and relapse to other locations is exceedingly rare.1,3,9 There are single reports on relapse affecting abdominal lymph nodes, bones including the jaw, mediastinum, orbit, gingival tissue, kidney, heart, and breast.1,9 When acute leukemia relapse occurs after allogeneic BMT, the disease is often more resistant to treatment, with generally poor prognosis. Most published studies report a median post-relapse survival time of about 8
e16
OOOOE May 2009
Bakathir and Al-Hamdani
months.1,10 This was the case in the present patient, who died 6 months after the diagnosis of the jaw relapse, owing to refractory disease. Many reported cases of ALL relapse in EM sites show that the relapse was often the first sign indicating relapse of leukemia, with or without simultaneous BM relapse.7-9 This was the finding in the present case, where the dental presentation in the jaw was the only indication for relapse of ALL in this patient. Oral complications occur frequently in leukemia and may be the presenting feature of the disease. Oral manifestations usually arise from an underlying thrombocytopenia, neutropenia, or impaired granulocyte function, or they may result from direct leukemic infiltration.11 Earlier reports have described a number of leukemic-induced oral changes, including pain, gingival swelling, bleeding, ulceration, bony changes, and infection. However, the oral manifestations specifically associated with relapse of ALL have been infrequently documented in the literature.5,7,8,11-13 Published case reports show that the features of oral relapse in ALL include numbness of the lip and chin, gingival tissue enlargement, jaw pain, and swelling.2,5,8,12,13 Relapse of leukemia presenting in the jaw is extremely rare. We are aware of a few isolated cases reported, with relapse being more commonly seen in children than in adults.1,4,7-9,13 This could be attributed to the existence of myelopoiesis in the jaw until after puberty, making it a potential site for leukemic infiltration and relapse, especially in the lower jaw.5,7,14 Jaw involvement in leukemia was first described in 1944.7 In 1971, Curtis,14 in his review of panoramic radiographs of 214 children with leukemias, demonstrated the dental and jaw abnormalities of patients with relapsed ALL on panoramic radiographs. These radiographic abnormalities varied in severity from obvious destruction of the dental crypts and lamina dura or displacement of teeth to more subtle changes in radiodensity of jaw and loss of the inferior dental canal lines. In the present case, the OPG clearly showed areas of ill-defined radiolucency in the maxillary and mandibular alveolar bone areas and the disappearance of the inferior dental canal lines bilaterally. In conclusion, the authors hope that this report serves as a reminder to those, particularly dentists, caring for survivors of leukemia, to be vigilant regarding complaints of jaw pain, swelling, or numbness. Although these symptoms may be of dental origin or the result of a side effect of chemotherapeutic treatment, they may
also be an important sign indicating the relapse of leukemia. In addition, the authors strongly stress the importance of regular dental reviews on these patients, even when in remission, and ideally in a specialist center, as part of their continuing multidisciplinary care. REFERENCES 1. Lee KH, Lee JH, Choi SJ, Lee JH, Kim S, Seol M, et al. Bone marrow vs extramedullary relapse of acute leukemia after allogeneic hematopoietic cell transplantation: risk factors and clinical course. Bone Marrow Transplant 2003;32:835-42. 2. Au WY, Wong KY, Leung RYY, Tong ACK. Isolated gingival relapse of acute lymphoblastic leukemia after transplantation. J Oral Pathol Med 2008;37:249-51. 3. Lee KH, Lee JH, Kim S, Lee JS, Kim SH, Kim WK. High frequency of extramedullary relapse of acute leukemia after allogeneic bone marrow transplantation. Bone Marrow Transplant 2000;26:147-52. 4. Benson RE, Rodd HD, North S, Loescher AR, Farthing PM, Payne M. Leukaemic infiltration of the mandible in a young girl. Int J Paediatr Dent 2007;17:145-50. 5. Huffman GG. Mandibular involvement in acute lymphocytic leukemia: report of a case. J Oral Surg 1976;34:842-5. 6. Nomura K, Okamoto T, Nakao M, Ueda K, Akano Y, Fujita Y, et al. Multiple bone lesions after allogeneic bone marrow transplantation in a patient with relapsed adult acute lymphoblastic leukemia: minimal residual disease analysis may predict extramedullary relapse. Leuk Lymphoma 2001;42:1305-8. 7. Williams SA, Duggan MB, Bailey CC. Jaw involvement in acute lymphoblastic leukaemia. Br Dent J 1983;155:164-6. 8. Hiraki A, Nakamura S, Abe K, Takenoshita Y, Horinouchi Y, Shinohara M, et al. Numb chin syndrome as an initial symptom of acute lymphocytic leukemia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;83:555-61. 9. Cunningham I. Extramedullary sites of leukemia relapse after transplant. Leuk Lymphoma 2006;47:1754-67. 10. Al Lamki Z, Wali YA, Shah WM, Zachariah M. Relapsed acute leukemia in children: Oman experience. Pediatr Hematol Oncol 2004;21:167-73. 11. Cousin GCS. Oral manifestations of leukaemia. Dent Update 1997;24:67-70. 12. Stafford R, Sonis S, Lockhart P, Sonis A. Oral pathoses as diagnostic indication in leukaemia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1980;50:134-9. 13. Bernstein ML, Schwartz S. Mandibular relapse in acute leukemia. Am J Pediatr Oncol 1986;8:240-4. 14. Curtis AB. Childhood leukemias: osseous changes in jaws on panoramic dental radiographs. J Am Dent Assoc 1971;83:844-7. Reprint requests: Abdulaziz A. Bakathir Oral Health Department Sultan Qaboos University Hospital Sultan Qaboos University P.O. Box 38, PC 123, Sultanate of Oman [email protected]