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B-cell lymphoma presenting as a midfacial necrotizing lesion
B-cell lymphoma presenting as a midfacial necrotizing lesion W, G. Maxymiw, DDS, B. J. Patterson, MD, CM, FRCPC, R. E. Wood, DOS, MSc, J. M. Meharchand, MB, CHB, FRCPC, A. J. Munro, MD, FRCPC, and I. G’orska-Flipot, PhD, Toronto, Ontario, Canada ONTARIO
CANCER
INSTITUTE,
PRINCESS
MARGARET
HOSPITAL
A case of midfacial necrotizing lesion (midline nonhealing granuloma) is reported. Paraffin- and frozen-section immunocytochemistry suggested a tumor of B-cell lineage and was confirmed by Southern blot analysis that disclosed an immunoglobulin heavy chain gene rearrangement with no evidence of T-cell receptor genetic aberration. The tumor was of B-cell lineage despite the tumor site and the angiocentric pattern, which are typically seen with peripheral T cell lymphoma with this presentation. (ORAL SURG ORAL MED ORAL PATHOL 1992;74:343-7)
N
ecrotizing lesionsof the upper airway can present diagnostic difficulties. The differential diagnosis of such lesions should include vasculitic diseases,granulomatous disorders, bacterial and protozoa1 infections, and neoplasms.’ Stewart2 in 1933 published the original article on the subject of these lesions and stated that they had no known causebut acceptedthat the disease was of granulomatous origin. He did, however, divide the diseaseinto three clinical stages: prodromal, active, and terminal. Classically the midline nonhealing granuloma presents as a localized destructive, nondescript, and nonspecific inflammatory lesion. It is relentlessly destructive of facial tissues and is not associated with visceral involvement in the initial stages.’ However, Batsakis and Luna’ believed that this lesion is an example of diagnosis by exclusion, wherein it may by virtue of its sensitivity to radiotherapy be an unrecognized lymphoma. They also believed that the lesion should be referred to as midfacial necrotizing lesion. Immunomorphologic analysis by many authors’, 3-9 indicates that this lesion is predominantly a peripheral T cell lymphoma.9 We report a caseof B cell lymphoma presenting as midfacial necrotizing lesion. CASEREPORT
Mrs. R., a 74-year-old Italian woman, had a 4-week history of nasal stuffiness. She also noticed a blister in the cen7/14/35502
ter of the apex of the hard palate. Her mouth and throat were painful when she swallowed, and she had pain radiating to the right cheek. A nasal examination revealed a markedly congestednose with polyps blocking the left nostril and a sessilegranulation-like growth present along the nasal septum and floor of the nose.A lesion was present on the hard palate and hadulceratedcompletelythroughto the nasal fossa. It had a firm, bulging, indurated peripheral border and measured 3.5 cm mesiodistally by 2.0 cm mediolaterally crossing the midline (Fig. 1). The patient had no palpable neck nodes. Radiographically the lesion had destroyed the apex of the hard palate (Fig. 2) and extended into the ethmoid air cells on the left side. The inferomedial wall of the left maxillary antrum was also destroyed. The patient was anesthetized with local anesthetic, and a section of the hard palate lesion was removedand sent for histopathologic investigation. The histopathologic sections (Fig. 3) demonstrated squamous mucosa with a submucosal infiltrate of small lymphocytes and large noncleaved cells between which mitoses and single cell necrosis were evident. Small vessels were prominent in all fields, and in someareasan angiocentric and angiodestructive pattern was present. Paraffin-section immunocytochemistry (Fig. 4) demonstrated that the large noncleaved cells were CD45 (leukocyte common antigen) positive, CD20 (L26) positive, CD45R (UCLHl)negative, CD43 (Leu-22) negative, cytoplasmic light chain negative, muramidase negative, chloro-acetate-esterase negative. The small lymphocytes were CD45 positive, CD45R positive, CD43 positive, CD20 negative, and cytoplasmic light chain negative. Frozen-section immunocytochemistry confirmed that the large cells were CD22 positive and CD2/3 negative. The tissue diagnosis was ma343
344
Maxymiw
Fig. ery.
et al.
0~4~
SURG ORAL
MLD ORAL PATHOI. September 1992
1. Clinical photograph illustrates degree of destruction of palate with soft tissue heaped along periph-
Fig. 2. Radiograph illustrates destruction of nasal floor.
lignant lymphoma of intermediate grade, diffuse, predominantly large cell. The paraffin- and frozen-section immunocytochemistry was interpreted as consistent with a tumor of B-cell lineage. Fig. 5 shows the molecular analysis of DNA from the patient’s tissue sample. DNA extracted from the patient and DNA from blood leukocytes of a normal healthy donor were digested with restriction enzyme EcoRI and hybridized to immunoglobulin-specific J, probe (lanes 1 and 2) and
the T-cell receptor-specific probe CB (lanes 3 and 4). A monoclonal rearrangement was detected by probe J, (lane 2, band R) only with the DNA extracted from the clinical sample and not with the control normal DNA (lane 1, band G), thus confirming the presence of monoclonal population of cells arising from a single clone containing specific rearrangement of one allele of the immunoglobulin heavy chain gene. This allowed classifying the tumor as a B cell lymphoma of clonal origin. The (3chain of the T-cell recep-
Volume 74 Number 3
B-cell lymphoma as midfacial
necrotizing lesion
345
Fig. 3. Angiocentric and angiodestructive infiltrate of small lymphocytes and large noncleaved cells with effacement of vessel wall (broad arrows) and narrowing of lumen (curved arrow). Hematoxylin-eosin stain; original magnification, X25.)
Fig. 4. Paraffin-section immunocytochemistry illustrates large noncleaved lymphoma cells with strong membrane CD20 (L26) positivity. (Original magnification, X64.) tor gene is in a germline configuration (lane 4, band G), as expected. Peripheral blood counts and a serum chemistry profile including lactate dehydrogenasewere normal. Chest x-ray films showed some chronic inflammatory changes of the lung basesbut no evidenceof a neoplastic lesion. X-ray film of the paranasal sinusesshowed that the sinuseswere clear but confirmed a soft tissue mass arising from the palate in the midline. Computed tomographic scan of the baseof the skull showed a large irregular soft tissue massinvolving the nasal cavity and extending from the posterior aspect of the
nose to the anterior aspect of the nasopharynx. The lesion extended into the ethmoid air cells, particularly on the left and inferiorly through the hard palate, with extensive bony destruction. There was also evidence of destruction of the inferomedial wall of the left maxillary antrum. Bilateral lymphangiogram and computed tomography of the abdomen and pelvis showed no evidence of lymphadenopathy. A bone marrow aspirate and biopsy showed no evidenceof involvement of lymphoma and examination of cerebrospinal fluid was negative for lymphoma cells. The patient was therefore clinical stage IE.
346
Maxymiw
rt al.
OKAL
SUKC,
OKhI.
idti,
ORAL
PA.1 HO1
September 1992
Fig. 5. Molecular analysis of patient’s tumor sample, EcoRI-digested DNA (lanes 2 and 41, and control normal DNA (lanes I and 3) were hybridized to immunoglobulinspecitic J, probe (lanes 1 and 21or T-cell receptor-specific cp probe (lanes 3 and 4). Bands designated G representgermline configuration, and band designated R represents clonal rearrangement of immunoglobulin gene. Although the lymphoma was clinically localized, the age of the patient and the bulk of diseaseled to a decision that the patient would be treated with combined modality treatment (chemotherapy and radiation). She therefore received three cycles of CHOP (cyclophosphamide, doxorubicin [ Adriamycin], vincristine, and prednisone) chemotherapy. Her first courseof chemotherapy was complicated by febrile neutropenia and esophagitis causedby herpessimplex virus. The complications respondedwell to broad-spectrum antibiotics and acyclovir. The second and third courses were therefore modified by a 30% dose reduction. Despite the dose reduction, the third course of chemotherapy was accompanied by a short episode of febrile neutropenia, requiring the patients admission to the hospital for broadspectrum antibiotic therapy. Computed tomogram of the nasopharynx obtained 2 weeks after the third course of chemotherapy showed virtual resolution of the tumor; the only remaining abnormality was a minor degreeof mucosal thickening, situated medially to the right aspect of the maxilla. Her chemotherapy was followed by a course of radiation therapy to the nasopharynx, consisting of 35 cGy in 20 fractions, given by a lateral parallel opposedpair. DISCUSSION Patients with midfacial necrotizing lesions usually have nasal stuffiness that may last years before the appearance of palatal or midline ulceration and bone
destruction. Patients of all ages are affected, with a female predominance (2:1).’ Sinusitis may be associated with toothache, loosening of teeth, and delay in healing of extraction sockets.‘0 Radiologic findings are of a soft tissue opacity with destruction of nasal bones and sinus walls.” Nelson et al.” divided the clinical course into three stages: (1) pain and nasal stuffiness with nonspecific ulceration of the upper respiratory tract, (2) extensive tissue necrosis and destruction with purulence, and (3) bacterial infection and fatigue with debilitation and eventual death. The necrosis in these lesions may be the result of the angioinfiltrative growth pattern. The cellular inhltrate is composed of small lymphocytes, immunoblasts, histiocytes, plasma cells, eosinophils, and scattered atypical cells. Surface ulceration and destruction is due to angiocentric infiltration.3 Batsakis and Luna’ believed that polymorphic reticulosis (PR) and lymphomatoid granulomatosis (LG) are extranodal lymphomas, predominantly of T-cell composition, and that the LG-PR T cell lymphomas are selective, with the lungs the primary target in LG and the midfacial region in PR. According to the working formulation,t3 both are usually classified as intermediate-grade diffuse mixed or diffuse large cell lymphomas. It is suspected that this lesion is a non-Hodgkin’s lymphoma, with T-cell origin being prominent, followed by B-cell.14 The T cell is usually of a small and large cell type, whereas the B cell is a pleomorphic centroblastic type with a diffuse growth pattern.t4 The Southern blot hybridization technique is used to diagnose B cell lymphoma by detecting clonal immunoglobulin gene rearrangements in neoplastic lymph node and other biopsy tissues.15 Hematopoietic cells undergo specific rearrangements of their immunoglobulin or T-cell receptors, because they are committed to a particular lineage. Thus B cells rearrange their immunoglobulin genes, and T cells undergo T-cell receptor rearrangement. Cells that have not initiated this process are undifferentiated.16 As a result, detection of rearrangement can be used as a tool to determine lineage. Rearranged light chain genes appear to be diagnostic of B-cell lineage,15 and occasionally heavy chain genes are rearranged in T-cell or myeloid neoplasms. The Southern blot analysis allows the assignation of non-Hodgkin’s lymphoma as either B or T cell, with the use of probes for the T-cell receptor and immunoglobulin subunits. This technique incorporates the isolation of intact cellular DNA, which is cut into fragments by restriction enzymes. These fragments are size-separated with agarose gel electro-
Volume 74 Number 3
phoresis. Fragments containing a particular sequence are detected with a radioactively labeled cloned DNA probe. In a normal polyclonal population of lymphocytes no single rearrangement pattern predominates; however, if more than 1% to 5% of the cells are of monoclonal origin, a single fragment is labeled above the background. l6 In this way a change in fragment size germline is used as a marker for a clone of cells derived from a particular lymphocyte. Experience has shown that chemotherapy (usually CHOP) should be given routinely with irradiation3T 5 The irradiation of diagnosed primary extranodal non-Hodgkin’s lymphoma achievesoptimal control at dosesof 3500 to 4000 cGy.” Prognosis declines with larger lesions, involvement of cervical lymph nodes, and recurrence of disease within 1 year.18 We thank Mr. K. Oxley, Mr. A. Connor, and Ms. K. Hahn for their assistance in preparing the illustrative material; Ms. J. Patterson for her secretarial assistance; Ms. C. Morrison and Mr. J. Jackson for referencematerial; and Dr. P. Leader and Dr. T. Mak for assistance in the molecular analysis. REFERENCES 1. Batsakis JG, Luna MA. Midfacial necrotizing lesions. Semin Diagn Pathol 1987;4:90-116. 2. Stewart JP. Progressivelethal granulomatous ulceration of the nose. J Laryngol Otol 1933;48:657-701. 3. Chott A, Rappersberger K, SchlossarekW, Radaszkiewicz T. Peripheral T cell lymphoma presenting primarily as lethal midline granuloma. Hum Pathol 1988;19:1093-101. 4. Gaulard P, Henni T, Marolleau J, et al. Lethal midline granuloma (polymorphic reticulosis) and lymphomatoid granulomatosis. Cancer 1988;62:705-10. 5. Harrison DFN. Midline destructive granuloma: fact or fiction? Laryngoscope 1987;97:1049-53. 6. Lippman SC, Grogan TM, Spier CM, et al. Lethal midline granuloma with a novel T-cell phenotype as found in peripheral T-cell lymphoma. Cancer 1987;59:936-9.
B-cell lymphoma as midfacial
necrotizing lesion
347
7. Platt J, Tomich C, Campbell S. Malignant lymphoma presenting as a midline lethal granuloma. J Oral Maxillofac Surg 1989;47:51l-3. 8. Whittaker S, Foroni L, Luzzato L, et al. Lymphomatoid granulomatosis: evidence of clonal T-cell origin and an association with lethal midline granuloma. Q J Meh 1988;68:645-55. 9. Yamanaka N. Kataura A. Minase T. Sambe S. Ishi Y. Midfacial T cell lymphoma: characterisation by monoclonal antibodies. Ann Otol Rhino1 Laryngol 1985;94:207-11. 10. Eveson JW, Slaney AE. Non-healing midline granuloma. Br J Oral Surg 1982;20:102-8. 11. Milford CA, Drake-Lee AB, LLoyd GS. Radiology of the paranasal sinusesin nonhealing granulomas of the nose. Clin Otolaryngol 1986;11:199-204. 12. Nelson JF, Finkelstein MW, Acevedo A, Gonzales GM. Midline “nonhealing” granuloma. ORAL SURG ORAL MED ORAL PATHOL 1984;58:554-60.
13. National Cancer Institute SponsoredStudy of Classification of Non-Hodgkin’s Lymphomas. Summary and description of working formulation for clinical usage. Cancer 1982;49:2112. 14. Laeng RH, Gerber HA, Schaffner T, Burki KH. Heterogeneous malignant non-Hodgkin’s lymphomas as a causative disorder in lethal midline granuloma. Virchows Arch [A] 1989;414:265-73. 15. Cleary ML, Chao J, Warnke R, Sklar J. Immunoglobulin gene rearrangement as a diagnostic criterion of B-cell lymphoma. Proc Nat1 Acad Sci USA 1984;81:593-7. 16. DeVita VT, Hellman S, RosenbergSA. Cancer: principles and practice of oncology. Grand Rapids, NY: JB Lippincott, 1989: 2489.
17. Sutcliffe SB, Gospodarowicz MK, Bush RS, et al. Role of radiation therapy in localized non-Hodgkin’s lymphoma. Radiother Oncol 1985;4:21l-23. 18. Pickens JP, Modica L. Current concepts of the lethal midline granuloma syndrome. Otolaryngol Head Neck Surg 1989; 100:623-30. Reprint requests:
W. G. Maxymiw, DDS Ontario Cancer Institute Princess Margaret Hospital 500 Sherbourne St. Toronto, Ontario Canada M4X lK9
CANCER
INSTITUTE,
PRINCESS
MARGARET
HOSPITAL
A case of midfacial necrotizing lesion (midline nonhealing granuloma) is reported. Paraffin- and frozen-section immunocytochemistry suggested a tumor of B-cell lineage and was confirmed by Southern blot analysis that disclosed an immunoglobulin heavy chain gene rearrangement with no evidence of T-cell receptor genetic aberration. The tumor was of B-cell lineage despite the tumor site and the angiocentric pattern, which are typically seen with peripheral T cell lymphoma with this presentation. (ORAL SURG ORAL MED ORAL PATHOL 1992;74:343-7)
N
ecrotizing lesionsof the upper airway can present diagnostic difficulties. The differential diagnosis of such lesions should include vasculitic diseases,granulomatous disorders, bacterial and protozoa1 infections, and neoplasms.’ Stewart2 in 1933 published the original article on the subject of these lesions and stated that they had no known causebut acceptedthat the disease was of granulomatous origin. He did, however, divide the diseaseinto three clinical stages: prodromal, active, and terminal. Classically the midline nonhealing granuloma presents as a localized destructive, nondescript, and nonspecific inflammatory lesion. It is relentlessly destructive of facial tissues and is not associated with visceral involvement in the initial stages.’ However, Batsakis and Luna’ believed that this lesion is an example of diagnosis by exclusion, wherein it may by virtue of its sensitivity to radiotherapy be an unrecognized lymphoma. They also believed that the lesion should be referred to as midfacial necrotizing lesion. Immunomorphologic analysis by many authors’, 3-9 indicates that this lesion is predominantly a peripheral T cell lymphoma.9 We report a caseof B cell lymphoma presenting as midfacial necrotizing lesion. CASEREPORT
Mrs. R., a 74-year-old Italian woman, had a 4-week history of nasal stuffiness. She also noticed a blister in the cen7/14/35502
ter of the apex of the hard palate. Her mouth and throat were painful when she swallowed, and she had pain radiating to the right cheek. A nasal examination revealed a markedly congestednose with polyps blocking the left nostril and a sessilegranulation-like growth present along the nasal septum and floor of the nose.A lesion was present on the hard palate and hadulceratedcompletelythroughto the nasal fossa. It had a firm, bulging, indurated peripheral border and measured 3.5 cm mesiodistally by 2.0 cm mediolaterally crossing the midline (Fig. 1). The patient had no palpable neck nodes. Radiographically the lesion had destroyed the apex of the hard palate (Fig. 2) and extended into the ethmoid air cells on the left side. The inferomedial wall of the left maxillary antrum was also destroyed. The patient was anesthetized with local anesthetic, and a section of the hard palate lesion was removedand sent for histopathologic investigation. The histopathologic sections (Fig. 3) demonstrated squamous mucosa with a submucosal infiltrate of small lymphocytes and large noncleaved cells between which mitoses and single cell necrosis were evident. Small vessels were prominent in all fields, and in someareasan angiocentric and angiodestructive pattern was present. Paraffin-section immunocytochemistry (Fig. 4) demonstrated that the large noncleaved cells were CD45 (leukocyte common antigen) positive, CD20 (L26) positive, CD45R (UCLHl)negative, CD43 (Leu-22) negative, cytoplasmic light chain negative, muramidase negative, chloro-acetate-esterase negative. The small lymphocytes were CD45 positive, CD45R positive, CD43 positive, CD20 negative, and cytoplasmic light chain negative. Frozen-section immunocytochemistry confirmed that the large cells were CD22 positive and CD2/3 negative. The tissue diagnosis was ma343
344
Maxymiw
Fig. ery.
et al.
0~4~
SURG ORAL
MLD ORAL PATHOI. September 1992
1. Clinical photograph illustrates degree of destruction of palate with soft tissue heaped along periph-
Fig. 2. Radiograph illustrates destruction of nasal floor.
lignant lymphoma of intermediate grade, diffuse, predominantly large cell. The paraffin- and frozen-section immunocytochemistry was interpreted as consistent with a tumor of B-cell lineage. Fig. 5 shows the molecular analysis of DNA from the patient’s tissue sample. DNA extracted from the patient and DNA from blood leukocytes of a normal healthy donor were digested with restriction enzyme EcoRI and hybridized to immunoglobulin-specific J, probe (lanes 1 and 2) and
the T-cell receptor-specific probe CB (lanes 3 and 4). A monoclonal rearrangement was detected by probe J, (lane 2, band R) only with the DNA extracted from the clinical sample and not with the control normal DNA (lane 1, band G), thus confirming the presence of monoclonal population of cells arising from a single clone containing specific rearrangement of one allele of the immunoglobulin heavy chain gene. This allowed classifying the tumor as a B cell lymphoma of clonal origin. The (3chain of the T-cell recep-
Volume 74 Number 3
B-cell lymphoma as midfacial
necrotizing lesion
345
Fig. 3. Angiocentric and angiodestructive infiltrate of small lymphocytes and large noncleaved cells with effacement of vessel wall (broad arrows) and narrowing of lumen (curved arrow). Hematoxylin-eosin stain; original magnification, X25.)
Fig. 4. Paraffin-section immunocytochemistry illustrates large noncleaved lymphoma cells with strong membrane CD20 (L26) positivity. (Original magnification, X64.) tor gene is in a germline configuration (lane 4, band G), as expected. Peripheral blood counts and a serum chemistry profile including lactate dehydrogenasewere normal. Chest x-ray films showed some chronic inflammatory changes of the lung basesbut no evidenceof a neoplastic lesion. X-ray film of the paranasal sinusesshowed that the sinuseswere clear but confirmed a soft tissue mass arising from the palate in the midline. Computed tomographic scan of the baseof the skull showed a large irregular soft tissue massinvolving the nasal cavity and extending from the posterior aspect of the
nose to the anterior aspect of the nasopharynx. The lesion extended into the ethmoid air cells, particularly on the left and inferiorly through the hard palate, with extensive bony destruction. There was also evidence of destruction of the inferomedial wall of the left maxillary antrum. Bilateral lymphangiogram and computed tomography of the abdomen and pelvis showed no evidence of lymphadenopathy. A bone marrow aspirate and biopsy showed no evidenceof involvement of lymphoma and examination of cerebrospinal fluid was negative for lymphoma cells. The patient was therefore clinical stage IE.
346
Maxymiw
rt al.
OKAL
SUKC,
OKhI.
idti,
ORAL
PA.1 HO1
September 1992
Fig. 5. Molecular analysis of patient’s tumor sample, EcoRI-digested DNA (lanes 2 and 41, and control normal DNA (lanes I and 3) were hybridized to immunoglobulinspecitic J, probe (lanes 1 and 21or T-cell receptor-specific cp probe (lanes 3 and 4). Bands designated G representgermline configuration, and band designated R represents clonal rearrangement of immunoglobulin gene. Although the lymphoma was clinically localized, the age of the patient and the bulk of diseaseled to a decision that the patient would be treated with combined modality treatment (chemotherapy and radiation). She therefore received three cycles of CHOP (cyclophosphamide, doxorubicin [ Adriamycin], vincristine, and prednisone) chemotherapy. Her first courseof chemotherapy was complicated by febrile neutropenia and esophagitis causedby herpessimplex virus. The complications respondedwell to broad-spectrum antibiotics and acyclovir. The second and third courses were therefore modified by a 30% dose reduction. Despite the dose reduction, the third course of chemotherapy was accompanied by a short episode of febrile neutropenia, requiring the patients admission to the hospital for broadspectrum antibiotic therapy. Computed tomogram of the nasopharynx obtained 2 weeks after the third course of chemotherapy showed virtual resolution of the tumor; the only remaining abnormality was a minor degreeof mucosal thickening, situated medially to the right aspect of the maxilla. Her chemotherapy was followed by a course of radiation therapy to the nasopharynx, consisting of 35 cGy in 20 fractions, given by a lateral parallel opposedpair. DISCUSSION Patients with midfacial necrotizing lesions usually have nasal stuffiness that may last years before the appearance of palatal or midline ulceration and bone
destruction. Patients of all ages are affected, with a female predominance (2:1).’ Sinusitis may be associated with toothache, loosening of teeth, and delay in healing of extraction sockets.‘0 Radiologic findings are of a soft tissue opacity with destruction of nasal bones and sinus walls.” Nelson et al.” divided the clinical course into three stages: (1) pain and nasal stuffiness with nonspecific ulceration of the upper respiratory tract, (2) extensive tissue necrosis and destruction with purulence, and (3) bacterial infection and fatigue with debilitation and eventual death. The necrosis in these lesions may be the result of the angioinfiltrative growth pattern. The cellular inhltrate is composed of small lymphocytes, immunoblasts, histiocytes, plasma cells, eosinophils, and scattered atypical cells. Surface ulceration and destruction is due to angiocentric infiltration.3 Batsakis and Luna’ believed that polymorphic reticulosis (PR) and lymphomatoid granulomatosis (LG) are extranodal lymphomas, predominantly of T-cell composition, and that the LG-PR T cell lymphomas are selective, with the lungs the primary target in LG and the midfacial region in PR. According to the working formulation,t3 both are usually classified as intermediate-grade diffuse mixed or diffuse large cell lymphomas. It is suspected that this lesion is a non-Hodgkin’s lymphoma, with T-cell origin being prominent, followed by B-cell.14 The T cell is usually of a small and large cell type, whereas the B cell is a pleomorphic centroblastic type with a diffuse growth pattern.t4 The Southern blot hybridization technique is used to diagnose B cell lymphoma by detecting clonal immunoglobulin gene rearrangements in neoplastic lymph node and other biopsy tissues.15 Hematopoietic cells undergo specific rearrangements of their immunoglobulin or T-cell receptors, because they are committed to a particular lineage. Thus B cells rearrange their immunoglobulin genes, and T cells undergo T-cell receptor rearrangement. Cells that have not initiated this process are undifferentiated.16 As a result, detection of rearrangement can be used as a tool to determine lineage. Rearranged light chain genes appear to be diagnostic of B-cell lineage,15 and occasionally heavy chain genes are rearranged in T-cell or myeloid neoplasms. The Southern blot analysis allows the assignation of non-Hodgkin’s lymphoma as either B or T cell, with the use of probes for the T-cell receptor and immunoglobulin subunits. This technique incorporates the isolation of intact cellular DNA, which is cut into fragments by restriction enzymes. These fragments are size-separated with agarose gel electro-
Volume 74 Number 3
phoresis. Fragments containing a particular sequence are detected with a radioactively labeled cloned DNA probe. In a normal polyclonal population of lymphocytes no single rearrangement pattern predominates; however, if more than 1% to 5% of the cells are of monoclonal origin, a single fragment is labeled above the background. l6 In this way a change in fragment size germline is used as a marker for a clone of cells derived from a particular lymphocyte. Experience has shown that chemotherapy (usually CHOP) should be given routinely with irradiation3T 5 The irradiation of diagnosed primary extranodal non-Hodgkin’s lymphoma achievesoptimal control at dosesof 3500 to 4000 cGy.” Prognosis declines with larger lesions, involvement of cervical lymph nodes, and recurrence of disease within 1 year.18 We thank Mr. K. Oxley, Mr. A. Connor, and Ms. K. Hahn for their assistance in preparing the illustrative material; Ms. J. Patterson for her secretarial assistance; Ms. C. Morrison and Mr. J. Jackson for referencematerial; and Dr. P. Leader and Dr. T. Mak for assistance in the molecular analysis. REFERENCES 1. Batsakis JG, Luna MA. Midfacial necrotizing lesions. Semin Diagn Pathol 1987;4:90-116. 2. Stewart JP. Progressivelethal granulomatous ulceration of the nose. J Laryngol Otol 1933;48:657-701. 3. Chott A, Rappersberger K, SchlossarekW, Radaszkiewicz T. Peripheral T cell lymphoma presenting primarily as lethal midline granuloma. Hum Pathol 1988;19:1093-101. 4. Gaulard P, Henni T, Marolleau J, et al. Lethal midline granuloma (polymorphic reticulosis) and lymphomatoid granulomatosis. Cancer 1988;62:705-10. 5. Harrison DFN. Midline destructive granuloma: fact or fiction? Laryngoscope 1987;97:1049-53. 6. Lippman SC, Grogan TM, Spier CM, et al. Lethal midline granuloma with a novel T-cell phenotype as found in peripheral T-cell lymphoma. Cancer 1987;59:936-9.
B-cell lymphoma as midfacial
necrotizing lesion
347
7. Platt J, Tomich C, Campbell S. Malignant lymphoma presenting as a midline lethal granuloma. J Oral Maxillofac Surg 1989;47:51l-3. 8. Whittaker S, Foroni L, Luzzato L, et al. Lymphomatoid granulomatosis: evidence of clonal T-cell origin and an association with lethal midline granuloma. Q J Meh 1988;68:645-55. 9. Yamanaka N. Kataura A. Minase T. Sambe S. Ishi Y. Midfacial T cell lymphoma: characterisation by monoclonal antibodies. Ann Otol Rhino1 Laryngol 1985;94:207-11. 10. Eveson JW, Slaney AE. Non-healing midline granuloma. Br J Oral Surg 1982;20:102-8. 11. Milford CA, Drake-Lee AB, LLoyd GS. Radiology of the paranasal sinusesin nonhealing granulomas of the nose. Clin Otolaryngol 1986;11:199-204. 12. Nelson JF, Finkelstein MW, Acevedo A, Gonzales GM. Midline “nonhealing” granuloma. ORAL SURG ORAL MED ORAL PATHOL 1984;58:554-60.
13. National Cancer Institute SponsoredStudy of Classification of Non-Hodgkin’s Lymphomas. Summary and description of working formulation for clinical usage. Cancer 1982;49:2112. 14. Laeng RH, Gerber HA, Schaffner T, Burki KH. Heterogeneous malignant non-Hodgkin’s lymphomas as a causative disorder in lethal midline granuloma. Virchows Arch [A] 1989;414:265-73. 15. Cleary ML, Chao J, Warnke R, Sklar J. Immunoglobulin gene rearrangement as a diagnostic criterion of B-cell lymphoma. Proc Nat1 Acad Sci USA 1984;81:593-7. 16. DeVita VT, Hellman S, RosenbergSA. Cancer: principles and practice of oncology. Grand Rapids, NY: JB Lippincott, 1989: 2489.
17. Sutcliffe SB, Gospodarowicz MK, Bush RS, et al. Role of radiation therapy in localized non-Hodgkin’s lymphoma. Radiother Oncol 1985;4:21l-23. 18. Pickens JP, Modica L. Current concepts of the lethal midline granuloma syndrome. Otolaryngol Head Neck Surg 1989; 100:623-30. Reprint requests:
W. G. Maxymiw, DDS Ontario Cancer Institute Princess Margaret Hospital 500 Sherbourne St. Toronto, Ontario Canada M4X lK9