Unusual lymphoblastic leukemia/lymphoma in Eastern Iran
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《美国医学杂志》
1 Department of Pathology, Ali Asghar Hospital, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran,2 Hematology and Oncology Unit, Department of Pediatric, Ali Asghar Hospital, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran,
Abstract
Lymphoblastic lymphoma-leukemia (LBLL) most commonly presents with mediastinal masses (50-75%), while pleural and pericardial effusion may also be present. Lymphadenopathy usually in the neck, axilla or supraclavicular regions, is considered as another typical presentation of the disease. This is a case report of a six-year-old boy with unusual huge enlargement of maxilla, mandible and soft palate as well as gingival hypertrophy which led to secondary respiratory and feeding difficulties. Morphologic and flowcytometric evaluation of bone marrow aspiration showed that it was a T cell type acute leukemia which may be due to dissemination of a lymphoblastic lymphoma and considered as a case of lymphoma-leukemia. After appropriate treatment, the symptoms of the patient relieved significantly and he is in complete remission for about one year.
Keywords: Lymphoblastic lymphoma; T cell type acute leukemia; Child; Eastern Iran
Lymphoblastic lymphoma as characterized by NCI working formulation, represents, at best, a small subset of those designated lymphoblastic in the first half of this century and were more recently included in the diffuse, poorly differentiated category of Rappaport.[1] Rappaport reported that his classification did not adequately address a subset of tumors occurring predominantly in children and young adults that was closely related to ALL.[2] With advent of immunologic techniques, precursors LBLL of either B-cell or T cell lineage were shown to be a close relationship between lymphoblastic lymphoma and ALL.[3] Approximately, 10-20% of all lymphoblastic lymphoma and 80-90% of all ALL have a precursor of pre-B or B cell immunophenotype in contrast to 80-90% of lymphoblastic lymphoma and 10-20% of ALL who have precursor of T cell lineage.[4], [5], [6] In both precursor B-cell and T cell LBLL, patients tend to be adolescents and among young adults, males outnumber females by a 2:1 ratio, and a common widespread supradiaphragmatic lymphadenopathy.[6], [7], [8] The patients B cell LBLL may be present in unusual sites including subdiaphragmatic lymph nodes, skin, bone and brain, but they rarely are presented with mediastinal masses[5], [9], [10], however, in T cell LBLL, mediastinal masses may occur in 50-80%[6] of the cases. Peripheral blood and bone marrow involvement are seen in at least one-third of patients with either T cell or B cell precursor LBLL and sometimes during the clinical courses among 80% of those who die from the disease[4]. Other well established sites of involvement include kidney, lung, ovary, testes, liver, spleen and eye.[11] Although involvement of jaw, maxilla and mandible is a well know finding in B cell type of non-Hodgkin lymphoma and LBLL, but only 3 documented cases were noticed in T cell type LBLL.[12], [13]
Here is reported a T cell type LBLL with a huge bulging of jaws as the only and primary presentation without any organomegaly or lymphadenopathy.
Case Report
A six years old boy was admitted in Ali Asghar Hospital of Zahedan University of Medical Sciences in Zahedan, Eastern Iran in 2002 with the chief complaint of huge enlargement of maxilla and mandible which produced severe respiratory and feeding problems Figure1. In his history, the main problem which led to investigations of dentists and otolaryngologists since 5 months prior to admission was progressive buldging of both maxilla and mandibule. He had mild pain and low grade fever without any other clinical findings (such as organomegaly and lymphadenopathy). CBC showed mild leukocytosis and ESR were between 35-75 but other laboratory findings were within normal limits. Jaw radiography showed a large soft tissue swelling at first and all of this findings led to misdiagnosis as a soft tissue infection and various therapies of different antibiotics were begun for him before admission in our hospital but the patient's problem progressed and his next plain graphies and paranasal sinus CT scan showed a hudge swelling with increased density and without any defined borders. Recent physical examination revealed huge enlargement of upper and lower jaw, gingival and soft palate hypertrophy resulted into feeding of patient as obligatory liquid diet. Neither lymphadenopathy nor organomegaly were detected and no enlargement of testes was noted. Abdominal sonography and CT scan of chest and abdomen showed neither para-aortic lymphadenopathy nor mediastinal masses.
The CBC and cytomorphology results where as follow: including Hb of 10.7 mg/dl, platelet of 157000/mm3 and WBC which was over 67000/mm3 with high N/C ratio. Fine chromatin pattern, conspicuous nucleolei and scanty cytoplasm were noticed. Figure2.
Gingival and mandibular biopsies were taken and processed according to Schaefer and showed sheets of almost monomorphic small tumoral cells invading soft tissue component and destruction of striated muscle fibers Figure3. The tumoral cells had round hyperchromatic nuclei, mostly with indistinct nucleolei, some with convoluted nuclear membrane and scanty cytoplasm. The mitotic figures were high and CD45 immunohistochmistry was positive.
Bone marrow aspiration and biopsy revealed marked cellularity with myeloid/erythroid maturation arrest and packed by monotonous small round cells of malignant tumor which had focal starry-sky appearance Figure4, in favor of leukemic transformation.
Flowcytometry of bone marrow aspiration was done table1 which revealed T cell type (CD2, CD4, CD45, CD7 and CD5 which all were positive) LBLL. Multiple CSF cytologic examinations were negative for malignancy. According to final diagnosis of acute T cell type LBLL, treatment of patient was begun by modified BFM 76/79 protocol and the chief complaint of patient was recovered significantly after one month Figure5. The patient was in complete remission for about one year and CBC was repeatedly undertaken which were within normal limits. Imaging studies did not demonstrate any pathological signs.
Discussion
Although there is not any comprehensive published data about the epidemiological and clinical findings of pediatric cancers (including NHL) in Iran, and pediatric cancer registeration has been started by Pediadteric Hematology & Oncolgy Society since 2004 (more details in www.iphos.ir) , however, regarding to literature unusual site of extramedulary involvement (such as kidney, lung, eyes, etc.) were seen mainly in B cell variants of lymphoma and leukemia rather than T cell type.[9], [10]
Involvement of maxilla and mandible occur frequently in Burkitts type lymphoma but as,mentioned before, it was reported only in 3 documented cases of T cell type LBLL.[12],[13] Oliver et al reported 2 clinical cases of jaw involvement (one of them was a 2 years old Down syndrome girl and another one was an adult male) with Burkitts-like lymphoma in cytomorphology, but they were immunophenotypicaly T cell type.[14] Other reports were an 18 month old boy with lower jaw involvement and a 15 month old boy with Crohn, disease and oral lesion who had cytomorpholigcal characteristics of lymphoblastic lymphoma and T cell type immunophenotype.[12], [13] None of the above cases progressed to leukemia. T cell type leukemia has formerely unfavorable prognostic feature due to change in treatment apporch, is no longer a poor risk factor.[14] In fact with many modern treatment programs, the T cell immunophenotype has become prognostically favorable.[15],[16],[17],[18]
In this case, although clinical and even histological findings may suggest a Burkitts' lymphoma or Bcell type LBL, we described a T cell type leukemia (based on immunoflowcytometric investigation), most probably as a progression of lymphoblastic lymphoma, with primary jaw involvement as the single extramedulary site without any organomegaly, which is very unusual in this type.
Therefore, we suggest that in addition to Burkitts lymphoma, enlargement of jaw may occur in T cell type of lymphoma and leukemia. Due to substantial improvement in survival due to improved protocols considering the histology,immunophenotype and staging of lymphoma, if patients are optimally managed,[15] immunophenotyping would be essential and mandatory to plan the protocol of treatment even in this so called discriminative and specific clinical finding.
References
1. Mograth IT. Malignant Lymphoma. In Leving AS, ed. Cancer in the Young. New York, Masson: 1982; 473.
2. Jaffe ES, Berard CW. Lymphoblastic lymphoma; a term rekindled with new precision. Ann Internal Med 1978; 89: 415.
3. Haris NL, Jaffe ES, Stein H. A revised European-American classification of lymphoid neoplasm, a proposal from international lymphoma Study Group. Blood 1994; 84: 1361.
4. Medeiros LJ. Intermediate and high grade lymphoma in the working formulation. In: Jaffe ES, ed. Surgical pathology of lymph nodes and related organs, major problem in pathology series . Vol. 16, 2nd Ed. Philadelphia, WB Saunders Co., 1994; 283.
5. Cossmanj-Chused TM, Fisher RI et al. Diversity of immunological phenotypes of lymphoblastic lymphoma. Cancer Res 1983; 43: 4486.
6. Weiss LM, Bindl JM, Picozzi VJ et al. Lymphoblastic lymphoma, an immunological phenotypes of 26 cases with comparison to T cell acute lymphoblastic leukemia. Blood 1986; 67: 474.
7. Nathwani BN, Kim H, Rappaport H. Malignant lymphoma, lymphoblastic. Cancer 1986; 38: 964.
8. Rosenberg SA, Berard CW, Brown BW et al. National cancer Institute sponsored study of classification of Non-Hodgkims lymphoma: summery and description of a working formulation for clinical usage. Cancer 1982; 49: 2112.
9. Sander C, Mederios LJ, Abruzzo LV et al. Lymphoblastic lymphoma presenting in cutaneous sites, a clinopathologic analysis of six cases. JANA Cad Dermatol 1991; 25 : 1023.
10. Sander CA, Jaffe ES, Gebhardt FC et al. Mediastinal lymphoblastic lymphoma with a immature B cell immunophenotype. In Philip A, David P, Poplack G. Principles and Practice of Pediatric Oncology. 3rd edition, Lippincott Raven Publishers, 1997: 426-427.
11. Wolvius EB, Van der Valk P, Baart JA et al. T cell lymphoblastic lymphoma of the lower jaw in a young child: a case report. Oral Surg Oral Med Oral Path
12. Scully C, Eveson JW, Witherow H, Young AH, Ton RS, Gilbey ED. Oral presentation of lymphoma. Eur J Cancer B Oral Oncol 1993; 29 : 225-229.
13. Oliver JD, Grogan TM, Pany CM, Spier C, Richter LC, Rangel CS. Burkitts-like lymphoma of T cell type. Mod Pathol 1998; 1 : 15-22.
14. Schauer P, Arlin ZA, Mertelsmann R et al. Treatment of acute lymphoblastic leukemia. J Clin Oncol 1997; 17 : 2461-2470.
15. Larson RA, Dodge RK, Burns CP et al. A five drug remission induction regimen with intensive consolidation for adult with acute lymphoblastic leukemia. cancer and leukemia group B study 8811. Blood 1995; 85 : 2025-2037.
16. Hoelzer D, Theil E, Loffler H et al. Intensified therapy in acute lymphoblastic and acute undifferentiated leukemia in adult. Blood 1984; 64 : 38-47.
17. Mandelli F, Annino L, Rotoli B. The GIMEMA ALL .183 trial: Analysis of 10 years follow up. GIMEMA cooperative Group, Italy. Br J Hematol 1996; 92 : 665-672.
18. Linker CA, Levitt LJO, Donnell M et al. Treatment of adult acute lymphoblastic leukemia with intensive cyclic chemotherapy: a follow up report. Blood 1997; 78: 2814-2822.(Karimi Mehrbod, Eshghi P)
Abstract
Lymphoblastic lymphoma-leukemia (LBLL) most commonly presents with mediastinal masses (50-75%), while pleural and pericardial effusion may also be present. Lymphadenopathy usually in the neck, axilla or supraclavicular regions, is considered as another typical presentation of the disease. This is a case report of a six-year-old boy with unusual huge enlargement of maxilla, mandible and soft palate as well as gingival hypertrophy which led to secondary respiratory and feeding difficulties. Morphologic and flowcytometric evaluation of bone marrow aspiration showed that it was a T cell type acute leukemia which may be due to dissemination of a lymphoblastic lymphoma and considered as a case of lymphoma-leukemia. After appropriate treatment, the symptoms of the patient relieved significantly and he is in complete remission for about one year.
Keywords: Lymphoblastic lymphoma; T cell type acute leukemia; Child; Eastern Iran
Lymphoblastic lymphoma as characterized by NCI working formulation, represents, at best, a small subset of those designated lymphoblastic in the first half of this century and were more recently included in the diffuse, poorly differentiated category of Rappaport.[1] Rappaport reported that his classification did not adequately address a subset of tumors occurring predominantly in children and young adults that was closely related to ALL.[2] With advent of immunologic techniques, precursors LBLL of either B-cell or T cell lineage were shown to be a close relationship between lymphoblastic lymphoma and ALL.[3] Approximately, 10-20% of all lymphoblastic lymphoma and 80-90% of all ALL have a precursor of pre-B or B cell immunophenotype in contrast to 80-90% of lymphoblastic lymphoma and 10-20% of ALL who have precursor of T cell lineage.[4], [5], [6] In both precursor B-cell and T cell LBLL, patients tend to be adolescents and among young adults, males outnumber females by a 2:1 ratio, and a common widespread supradiaphragmatic lymphadenopathy.[6], [7], [8] The patients B cell LBLL may be present in unusual sites including subdiaphragmatic lymph nodes, skin, bone and brain, but they rarely are presented with mediastinal masses[5], [9], [10], however, in T cell LBLL, mediastinal masses may occur in 50-80%[6] of the cases. Peripheral blood and bone marrow involvement are seen in at least one-third of patients with either T cell or B cell precursor LBLL and sometimes during the clinical courses among 80% of those who die from the disease[4]. Other well established sites of involvement include kidney, lung, ovary, testes, liver, spleen and eye.[11] Although involvement of jaw, maxilla and mandible is a well know finding in B cell type of non-Hodgkin lymphoma and LBLL, but only 3 documented cases were noticed in T cell type LBLL.[12], [13]
Here is reported a T cell type LBLL with a huge bulging of jaws as the only and primary presentation without any organomegaly or lymphadenopathy.
Case Report
A six years old boy was admitted in Ali Asghar Hospital of Zahedan University of Medical Sciences in Zahedan, Eastern Iran in 2002 with the chief complaint of huge enlargement of maxilla and mandible which produced severe respiratory and feeding problems Figure1. In his history, the main problem which led to investigations of dentists and otolaryngologists since 5 months prior to admission was progressive buldging of both maxilla and mandibule. He had mild pain and low grade fever without any other clinical findings (such as organomegaly and lymphadenopathy). CBC showed mild leukocytosis and ESR were between 35-75 but other laboratory findings were within normal limits. Jaw radiography showed a large soft tissue swelling at first and all of this findings led to misdiagnosis as a soft tissue infection and various therapies of different antibiotics were begun for him before admission in our hospital but the patient's problem progressed and his next plain graphies and paranasal sinus CT scan showed a hudge swelling with increased density and without any defined borders. Recent physical examination revealed huge enlargement of upper and lower jaw, gingival and soft palate hypertrophy resulted into feeding of patient as obligatory liquid diet. Neither lymphadenopathy nor organomegaly were detected and no enlargement of testes was noted. Abdominal sonography and CT scan of chest and abdomen showed neither para-aortic lymphadenopathy nor mediastinal masses.
The CBC and cytomorphology results where as follow: including Hb of 10.7 mg/dl, platelet of 157000/mm3 and WBC which was over 67000/mm3 with high N/C ratio. Fine chromatin pattern, conspicuous nucleolei and scanty cytoplasm were noticed. Figure2.
Gingival and mandibular biopsies were taken and processed according to Schaefer and showed sheets of almost monomorphic small tumoral cells invading soft tissue component and destruction of striated muscle fibers Figure3. The tumoral cells had round hyperchromatic nuclei, mostly with indistinct nucleolei, some with convoluted nuclear membrane and scanty cytoplasm. The mitotic figures were high and CD45 immunohistochmistry was positive.
Bone marrow aspiration and biopsy revealed marked cellularity with myeloid/erythroid maturation arrest and packed by monotonous small round cells of malignant tumor which had focal starry-sky appearance Figure4, in favor of leukemic transformation.
Flowcytometry of bone marrow aspiration was done table1 which revealed T cell type (CD2, CD4, CD45, CD7 and CD5 which all were positive) LBLL. Multiple CSF cytologic examinations were negative for malignancy. According to final diagnosis of acute T cell type LBLL, treatment of patient was begun by modified BFM 76/79 protocol and the chief complaint of patient was recovered significantly after one month Figure5. The patient was in complete remission for about one year and CBC was repeatedly undertaken which were within normal limits. Imaging studies did not demonstrate any pathological signs.
Discussion
Although there is not any comprehensive published data about the epidemiological and clinical findings of pediatric cancers (including NHL) in Iran, and pediatric cancer registeration has been started by Pediadteric Hematology & Oncolgy Society since 2004 (more details in www.iphos.ir) , however, regarding to literature unusual site of extramedulary involvement (such as kidney, lung, eyes, etc.) were seen mainly in B cell variants of lymphoma and leukemia rather than T cell type.[9], [10]
Involvement of maxilla and mandible occur frequently in Burkitts type lymphoma but as,mentioned before, it was reported only in 3 documented cases of T cell type LBLL.[12],[13] Oliver et al reported 2 clinical cases of jaw involvement (one of them was a 2 years old Down syndrome girl and another one was an adult male) with Burkitts-like lymphoma in cytomorphology, but they were immunophenotypicaly T cell type.[14] Other reports were an 18 month old boy with lower jaw involvement and a 15 month old boy with Crohn, disease and oral lesion who had cytomorpholigcal characteristics of lymphoblastic lymphoma and T cell type immunophenotype.[12], [13] None of the above cases progressed to leukemia. T cell type leukemia has formerely unfavorable prognostic feature due to change in treatment apporch, is no longer a poor risk factor.[14] In fact with many modern treatment programs, the T cell immunophenotype has become prognostically favorable.[15],[16],[17],[18]
In this case, although clinical and even histological findings may suggest a Burkitts' lymphoma or Bcell type LBL, we described a T cell type leukemia (based on immunoflowcytometric investigation), most probably as a progression of lymphoblastic lymphoma, with primary jaw involvement as the single extramedulary site without any organomegaly, which is very unusual in this type.
Therefore, we suggest that in addition to Burkitts lymphoma, enlargement of jaw may occur in T cell type of lymphoma and leukemia. Due to substantial improvement in survival due to improved protocols considering the histology,immunophenotype and staging of lymphoma, if patients are optimally managed,[15] immunophenotyping would be essential and mandatory to plan the protocol of treatment even in this so called discriminative and specific clinical finding.
References
1. Mograth IT. Malignant Lymphoma. In Leving AS, ed. Cancer in the Young. New York, Masson: 1982; 473.
2. Jaffe ES, Berard CW. Lymphoblastic lymphoma; a term rekindled with new precision. Ann Internal Med 1978; 89: 415.
3. Haris NL, Jaffe ES, Stein H. A revised European-American classification of lymphoid neoplasm, a proposal from international lymphoma Study Group. Blood 1994; 84: 1361.
4. Medeiros LJ. Intermediate and high grade lymphoma in the working formulation. In: Jaffe ES, ed. Surgical pathology of lymph nodes and related organs, major problem in pathology series . Vol. 16, 2nd Ed. Philadelphia, WB Saunders Co., 1994; 283.
5. Cossmanj-Chused TM, Fisher RI et al. Diversity of immunological phenotypes of lymphoblastic lymphoma. Cancer Res 1983; 43: 4486.
6. Weiss LM, Bindl JM, Picozzi VJ et al. Lymphoblastic lymphoma, an immunological phenotypes of 26 cases with comparison to T cell acute lymphoblastic leukemia. Blood 1986; 67: 474.
7. Nathwani BN, Kim H, Rappaport H. Malignant lymphoma, lymphoblastic. Cancer 1986; 38: 964.
8. Rosenberg SA, Berard CW, Brown BW et al. National cancer Institute sponsored study of classification of Non-Hodgkims lymphoma: summery and description of a working formulation for clinical usage. Cancer 1982; 49: 2112.
9. Sander C, Mederios LJ, Abruzzo LV et al. Lymphoblastic lymphoma presenting in cutaneous sites, a clinopathologic analysis of six cases. JANA Cad Dermatol 1991; 25 : 1023.
10. Sander CA, Jaffe ES, Gebhardt FC et al. Mediastinal lymphoblastic lymphoma with a immature B cell immunophenotype. In Philip A, David P, Poplack G. Principles and Practice of Pediatric Oncology. 3rd edition, Lippincott Raven Publishers, 1997: 426-427.
11. Wolvius EB, Van der Valk P, Baart JA et al. T cell lymphoblastic lymphoma of the lower jaw in a young child: a case report. Oral Surg Oral Med Oral Path
12. Scully C, Eveson JW, Witherow H, Young AH, Ton RS, Gilbey ED. Oral presentation of lymphoma. Eur J Cancer B Oral Oncol 1993; 29 : 225-229.
13. Oliver JD, Grogan TM, Pany CM, Spier C, Richter LC, Rangel CS. Burkitts-like lymphoma of T cell type. Mod Pathol 1998; 1 : 15-22.
14. Schauer P, Arlin ZA, Mertelsmann R et al. Treatment of acute lymphoblastic leukemia. J Clin Oncol 1997; 17 : 2461-2470.
15. Larson RA, Dodge RK, Burns CP et al. A five drug remission induction regimen with intensive consolidation for adult with acute lymphoblastic leukemia. cancer and leukemia group B study 8811. Blood 1995; 85 : 2025-2037.
16. Hoelzer D, Theil E, Loffler H et al. Intensified therapy in acute lymphoblastic and acute undifferentiated leukemia in adult. Blood 1984; 64 : 38-47.
17. Mandelli F, Annino L, Rotoli B. The GIMEMA ALL .183 trial: Analysis of 10 years follow up. GIMEMA cooperative Group, Italy. Br J Hematol 1996; 92 : 665-672.
18. Linker CA, Levitt LJO, Donnell M et al. Treatment of adult acute lymphoblastic leukemia with intensive cyclic chemotherapy: a follow up report. Blood 1997; 78: 2814-2822.(Karimi Mehrbod, Eshghi P)