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Hemorrhagic lymphadenopathy as a presenting feature of primary al amyloidosis
Pathology (2000) 32, pp. 21– 23
HEMORRHAGIC LYMPHADENOPATHY AS A PRESENTING FEATURE OF PRIMARY AL AMYLOIDOSIS JOHN P. HANLEY *, FERGUS R. MAC LEAN *, JANE L. EVA NS †, BARRY M. COLLS ‡, BRIDGET A. ROBINSON ‡, W. NIGEL PATTON * AND DAV ID C. HEATON * Departments of Haematology*, Anatomical Pathology† and The Oncology Service‡, Christchurch Hospital, New Zealand
Summary Lymphadenopathy associated with hemorrhage as a presenting feature of primary (AL) amyloidosis has not previously been described. We report two such cases one of whom had an acquired factor X and IX deficiency. The clinical presentations were characterized by sudden spontaneou s enlargement of lymph nodes followed by partial regression. In both cases significant delay in diagnosis, and hence treatment, occurred due to the mode of presentation. One patient died with rapidly progressive disease but the other has had an excellent response to therapy with high-dose melphalan (HDM, 200 mg/m2 ) and peripheral blood stem cell rescue. AL amyloid should be considered in all patients presenting with hemorrhagic lymphadenopath y. Key words: Amyloid, hemorrhagic lymphadenopath y Accepted 23 September 1999
INTRODUCTION Primary AL amyloidosis (amyloid due to the deposition of light chains) may involve a wide variety of organs which results in diverse clinical features at presentation.1 The majority of patients have evidence of cardiac, renal or neurological involvement.2 Hepatomegaly and splenomegaly are often present, but lymphadenopathy is less common. Bleeding problems occur in approximately 40% of cases.3 This is most often due to the direct effect of amyloid infiltration in blood vessels or more rarely acquired coagulation factor deficiencies. Acquired factor X deficiency4 is the classical bleeding disorder associated with AL amyloidosis although acquired factor IX deficiency5 has also been reported. Lymphadenopathy associated with hemorrhage has not previously been reported as a presenting feature of AL amyloidosis. We report two cases of AL amyloidosis with hemorrhagic lymphadenopathy. In one case an acquired factor IX and X deficiency was also present.
Case 1 A 52-yr-old male presented in February 1997 with abdominal pain. An ultrasound scan revealed a normal liver, bile ducts and gall bladder, but a well-defined mass was detected in the head of the pancreas. On CT scan this was shown to be a hemorrhagic mass and a further hemorrhagic area
was seen at the lower end of the esophagus. The pain settled and follow-up CT scan showed regression of the pancreatic and esophageal masses. Endoscopic retrograde cholangio-pancreaticography (ERCP) revealed a slightly dilated pancreatic duct with a normal cholangiogram. He then developed cervical lymphadenopathy and progressive weight loss. The lymph nodes varied in size over a period of time, undergoing sudden enlargement followed by spontaneous regression. A fine needle aspirate of an enlarged cervical lymph node revealed blood only. Subsequently spontaneous bruising of the upper limbs and a swelling in the right biceps muscle developed. The hemoglobin was 103 g/l (NR 135–175 g/l), the white cell count 6.8 ´ 10 9 /l (NR 4–11 ´ 109 /l), the platelet count 633 ´ 10 9 /l (NR 150– 400 ´ 109 /l), the prothrombin ratio 1.9 (NR 0.8–1.2), APTT 54 s (NR 26–36 s), the thrombin clotting time 23 s (NR 18– 22 s), fibrinogen and d-dimer normal, alkaline phosphatase 413 U/l (NR 30–120 U/l), g-glutamyl transferase 216 U/l (NR 10– 50 U/l), alanine aminotransferas e 48 U/l (NR 0– 40 U/l), bilirubin 48 μmol/l (NR 3– 21 μmol/l). The prothrombin time failed to correct following the administration of vitamin K. Immunoglobulin levels were normal but serum electrophoresis demonstrated a small monoclonal band (IgG l paraprotein). A trace amount of l light chains was detected in the urine. A bone marrow examination showed increased plasma cells (9%), but fluorescent immunophenotyping for k and l light chain expression did not detect a clonal population. Skeletal radiographs were normal but follow-up CT scanning revealed cervical, paratracheal and hilar lymphadenopathy and hepatosplenomegal y. A cervical lymph node biopsy was then performed, which revealed extensive areas of hemorrhagic infarction with no other diagnostic abnormality seen. There was prolonged post-operative bleeding from the biopsy site which prompted detailed coagulation studies. Factor X (11%) and factor IX (48%) were reduced but factor V (84%) and factor VIII (169%) were normal. This pattern of results suggested a diagnosis of AL amyloidosis; however, Congo red staining of the lymph node biopsy was negative and further invasive investigations were considered too hazardous. He received chemotherapy (cyclophospha mide, vincristine and prednisone6 ) but there was rapid clinical deterioration. At post mortem, extensive amyloid deposits were seen in the liver (Figs. 1 and 2) and spleen with smaller deposits noted in lymph nodes and kidneys. Fresh and old hemorrhage was present in lymph nodes but no hemorrhage was present in the other organs infiltrated with amyloid.
Case 2 A 42-year-old male presented in April 1996 with chest pain. An ECG revealed atrial fibrillation without evidence of myocardial infarction. He received treatment with sotalol and warfarin. Subsequent DC cardioversion failed to restore sinus rhythm. He remained well until August 1997 when he developed inguinal and axillary lymphadenopathy and hepatomegal y. The lymph nodes were intermittently palpable and underwent periods of sudden enlargement and spontaneous regression. A lymph node biopsy revealed areas of fresh and
ISSN 0031–3025 printed/ISSN 1465– 3931 online/00/010021 – 03 © 1999 Royal College of Pathologists of Australasia
22
Pathology (2000), 32, February
HANLEY et al.
Fig. 1 Case 1: liver at postmortem of Case 1 showing extensive red deposites of amyloid in sinusoids with atrophy of hepatocytes (Congo Red, ´ 100).
Fig. 3 Case 2: antral gastric mucosa showing extensive blue/green amyloid deposits in the lamina propria (Sulphated Alcian Blue, ´ 200).
older hemorrhage as well as extensive amyloid deposition demonstrated by Congo red staining. Hematological and biochemical investigations were carried out: hemoglobin 123 g/l, white cell count and platelet count normal, prothrombin ratio normal, APTT 25 s, thrombin clotting time normal, fibrinogen 8.0 g/l (NR 1.5–4 g/l), d-dimer normal, alkaline phosphatas e 176 U/l with otherwise normal liver function tests. Immunoglobulins were normal. Serum electrophoresis showed no paraprotein, but a trace amount of k light chains was detected in the urine. A bone marrow examination showed increased plasma cells (10%), positive by immunofluorescence for k light chains (which are relatively uncommon in primary amyloid1 ). Skeletal radiographs were normal. Further investigation revealed amyloid deposition in the gastro-intestinal tract (via esophageal, gastric (Fig. 3) and duodenal biopsies) and probable cardiac involvement (evidenced by echocardiogram and electrocardiogram). Coagulation screen and factor X assay (145%) were normal. CT scanning showed evidence of intraabdominal lymphadenopathy . In view of the multi-organ involvement and progressive nature of the disease he received high-dose melphalan therapy (200 mg/m2 ) with peripheral blood stem sell rescue. The procedure was complicated by selflimiting gastrointestinal toxicity and an episode of catheter-related sepsis, but he remains well six months post-treatment. Successful DC cardioversion to sinus rhythm has been achieved. There has been complete resolution of his peripheral lymphadenopathy and partial resolution of his hepatomegaly and intra-abdominal lymphadenopath y. However, the alkaline phosphatase remains elevated and his urine shows a trace of Bence Jones protein k type. A repeat bone marrow biopsy showed no increase of plasma cells, although immunophenotyping suggested the presence of a clonal population of plasma cells similar to that found at diagnosis.
DISCUSSION
Fig. 2 Case 1: characteristic apple-green birefringence of amyloid deposits in the liver at postmortem (Congo Red, ´ 100, polarized light).
The diverse clinical manifestations of primary (AL) amyloidosis include hemorrhage and lymphadenopathy. The hemorrhagic tendency is usually due to amyloid infiltration of blood vessels or more rarely specific acquired coagulation deficiencies. Amyloid-associated lymphadenopathy may be isolated7,8 or part of multi-system involvement. 2 The lymph node changes observed in amyloidosis have been described in detail,9 but the specific feature of hemorrhagic lymphadenopathy as a presenting feature of amyloidosis has not been described in the literature. In our two cases this was a prominent clinical manifestation of the disease. The observation of sudden lymph node enlargement followed by spontaneous partial regression is suggestive of recurrent hemorrhage within the amyloid infiltrated node. In both cases there was some delay in diagnosis. Only when the acquired coagulation deficiencies were correctly identified was the diagnosis of AL amyloidosis considered in the first case. In this case the ante-mortem lymph node biopsy revealed such extensive hemorrhagic infarction that any associated amyloid deposition was not detected. Postmortem studies clearly demonstrated the presence of amyloid deposition in lymph nodes. It is likely that the amyloid-associated coagulopathy accentuated the degree of hemorrhage and obscured underlying amyloid deposition in the lymph nodes sampled. Hemorrhagic features within lymph nodes are extremely uncommon. Hemorrhage may occasionally occur in malignant lymphadenopathy in association with tumor necrosis and has been described as a specific feature in spindle-cell tumor (a benign tumor often confused with Kaposi’s sarcoma).10 The treatment of AL amyloidosis remains unsatisfactory. Some patients respond to low-dose chemotherapy, but in general the outlook is poor.11 Encouraging results have recently been reported using high-dose chemotherapy with autologous peripheral blood stem cell support12 and there may be a role for allogeneic bone marrow transplantation. 13 In view of the possibility of such beneficial intensive treatment for patients with AL amyloidosis, early diagnosis
HEMORRHAGIC LYMPHADENOPATHY IN PRIMARY AMYLOIDOSIS
is essential. Due to the wide variety of clinical presentations of AL amyloidosis there may be diagnostic delay. This may have serious implications for the patient as AL amyloidosis is often rapidly progressive. The observation of hemorrhagic changes within lymph node biopsies should prompt the consideration of AL amyloidois as the underlying diagnosis. In the presence of an associated coagulopathy invasive diagnostic biopsy may be hazardous, but an abdominal fat aspiration has been reported as a useful diagnostic tool in this situation.14 AC KN OW LED GEM ENTS The authors thank Joy Monteath and staff (Immunophenotyping Laboratory, Canterbury Health Labs, Christchurch, New Zealand) for diagnostic expertise in the cases presented. Address for correspondence: Dr D. Hanley, Department of Haematology, Canterbury Health Laboratories, PO Box 151, Christchurch, New Zealand. e-mail: [email protected] z
References 1. Falk RH, Comenzo RL, Skinner M. The Systemic Amyloidoses. New Engl J Med 1997; 337: 898–909. 2. Kyle RA, Gertz MA. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol 1995; 32: 45–59. 3. Yood RA, Skinner M, Rubinow A, et al. Bleeding manifestations in 100 patients with amyloidosis. J Am Med Assoc 1983; 249: 1322–4.
23
4. Griepp PR, Kyle RA, Bowie EJW. Factor X deficiency in amyloidosis: a critical review. Am J Hematol 1981; 11: 443–50. 5. McPherson RA, Onstad JW, Ugoretz RJ, Wolf PL. Coagulopathy in amyloidosis: combined deficiencies of factors IX and X. Am J Hematol 1977; 3: 225– 35. 6. Bagley CM Jr, Devita VT Jr, Berard CW, Canellos GP. Advanced lymphosarcoma: intensive cyclical combination chemotherapy with cyclophosphamide, vincristine, and prednisone. Ann Int Med 1974; 76: 227– 34. 7. Spitale LS, Jimenez DB, Montenegro RB. Localised primary amyloidosis of inguinal lymph node with superimposed bone metaplasia. Pathology 1998; 30: 321– 2. 8. Kahn H, Strauchen JA, Gilbert HS, Fuchs A. Immunoglobulin-relate d amyloidosis presenting as recurrent isolated lymph node involvement . Arch Pathol Lab Med 1991; 115: 948–50. 9. Newland JR, Linke RP, Lennert K. Amyloid deposits in lymph nodes: a morphologic and immunohistochemical study. Hum Pathol 1986; 17: 1245– 9. 10. Suster S, Rosai J. Intranodal hemorrhagic spindle-cell tumor with ‘amiathoid’ fibers. Am J Surg Pathol 1989; 13: 347–57. 11. Kyle RA, Gertz MA, Greipp PR, et al. A trial of three regimens for primary amyloidosis: colchicine alone, melphalan and prednisone, and melphalan, prednisone and colchicine. New Engl J Med 1997; 336: 1202– 7. 12. Comenzo RL, Vosburgh E, Falk RH, et al. Dose-intensive melphalan with blood stem cell support for the treatment of AL (amyloid lightchain) amyloidosis: survival and responses in 25 patients. Blood 1998; 91: 3662–70. 13. Gillmore JD, Davies J, Iqbal A, et al. Allogeneic bone marrow transplantation for systemic AL amyloidosis. Br J Haematol 1998; 100: 226–8. 14. Duston MA, Skinner M, Shirahama T, Cohen AS. Diagnosis of amyloidosis by abdominal fat aspiration: analysis of four years experience. Am J Med 1987; 82: 412– 4.
HEMORRHAGIC LYMPHADENOPATHY AS A PRESENTING FEATURE OF PRIMARY AL AMYLOIDOSIS JOHN P. HANLEY *, FERGUS R. MAC LEAN *, JANE L. EVA NS †, BARRY M. COLLS ‡, BRIDGET A. ROBINSON ‡, W. NIGEL PATTON * AND DAV ID C. HEATON * Departments of Haematology*, Anatomical Pathology† and The Oncology Service‡, Christchurch Hospital, New Zealand
Summary Lymphadenopathy associated with hemorrhage as a presenting feature of primary (AL) amyloidosis has not previously been described. We report two such cases one of whom had an acquired factor X and IX deficiency. The clinical presentations were characterized by sudden spontaneou s enlargement of lymph nodes followed by partial regression. In both cases significant delay in diagnosis, and hence treatment, occurred due to the mode of presentation. One patient died with rapidly progressive disease but the other has had an excellent response to therapy with high-dose melphalan (HDM, 200 mg/m2 ) and peripheral blood stem cell rescue. AL amyloid should be considered in all patients presenting with hemorrhagic lymphadenopath y. Key words: Amyloid, hemorrhagic lymphadenopath y Accepted 23 September 1999
INTRODUCTION Primary AL amyloidosis (amyloid due to the deposition of light chains) may involve a wide variety of organs which results in diverse clinical features at presentation.1 The majority of patients have evidence of cardiac, renal or neurological involvement.2 Hepatomegaly and splenomegaly are often present, but lymphadenopathy is less common. Bleeding problems occur in approximately 40% of cases.3 This is most often due to the direct effect of amyloid infiltration in blood vessels or more rarely acquired coagulation factor deficiencies. Acquired factor X deficiency4 is the classical bleeding disorder associated with AL amyloidosis although acquired factor IX deficiency5 has also been reported. Lymphadenopathy associated with hemorrhage has not previously been reported as a presenting feature of AL amyloidosis. We report two cases of AL amyloidosis with hemorrhagic lymphadenopathy. In one case an acquired factor IX and X deficiency was also present.
Case 1 A 52-yr-old male presented in February 1997 with abdominal pain. An ultrasound scan revealed a normal liver, bile ducts and gall bladder, but a well-defined mass was detected in the head of the pancreas. On CT scan this was shown to be a hemorrhagic mass and a further hemorrhagic area
was seen at the lower end of the esophagus. The pain settled and follow-up CT scan showed regression of the pancreatic and esophageal masses. Endoscopic retrograde cholangio-pancreaticography (ERCP) revealed a slightly dilated pancreatic duct with a normal cholangiogram. He then developed cervical lymphadenopathy and progressive weight loss. The lymph nodes varied in size over a period of time, undergoing sudden enlargement followed by spontaneous regression. A fine needle aspirate of an enlarged cervical lymph node revealed blood only. Subsequently spontaneous bruising of the upper limbs and a swelling in the right biceps muscle developed. The hemoglobin was 103 g/l (NR 135–175 g/l), the white cell count 6.8 ´ 10 9 /l (NR 4–11 ´ 109 /l), the platelet count 633 ´ 10 9 /l (NR 150– 400 ´ 109 /l), the prothrombin ratio 1.9 (NR 0.8–1.2), APTT 54 s (NR 26–36 s), the thrombin clotting time 23 s (NR 18– 22 s), fibrinogen and d-dimer normal, alkaline phosphatase 413 U/l (NR 30–120 U/l), g-glutamyl transferase 216 U/l (NR 10– 50 U/l), alanine aminotransferas e 48 U/l (NR 0– 40 U/l), bilirubin 48 μmol/l (NR 3– 21 μmol/l). The prothrombin time failed to correct following the administration of vitamin K. Immunoglobulin levels were normal but serum electrophoresis demonstrated a small monoclonal band (IgG l paraprotein). A trace amount of l light chains was detected in the urine. A bone marrow examination showed increased plasma cells (9%), but fluorescent immunophenotyping for k and l light chain expression did not detect a clonal population. Skeletal radiographs were normal but follow-up CT scanning revealed cervical, paratracheal and hilar lymphadenopathy and hepatosplenomegal y. A cervical lymph node biopsy was then performed, which revealed extensive areas of hemorrhagic infarction with no other diagnostic abnormality seen. There was prolonged post-operative bleeding from the biopsy site which prompted detailed coagulation studies. Factor X (11%) and factor IX (48%) were reduced but factor V (84%) and factor VIII (169%) were normal. This pattern of results suggested a diagnosis of AL amyloidosis; however, Congo red staining of the lymph node biopsy was negative and further invasive investigations were considered too hazardous. He received chemotherapy (cyclophospha mide, vincristine and prednisone6 ) but there was rapid clinical deterioration. At post mortem, extensive amyloid deposits were seen in the liver (Figs. 1 and 2) and spleen with smaller deposits noted in lymph nodes and kidneys. Fresh and old hemorrhage was present in lymph nodes but no hemorrhage was present in the other organs infiltrated with amyloid.
Case 2 A 42-year-old male presented in April 1996 with chest pain. An ECG revealed atrial fibrillation without evidence of myocardial infarction. He received treatment with sotalol and warfarin. Subsequent DC cardioversion failed to restore sinus rhythm. He remained well until August 1997 when he developed inguinal and axillary lymphadenopathy and hepatomegal y. The lymph nodes were intermittently palpable and underwent periods of sudden enlargement and spontaneous regression. A lymph node biopsy revealed areas of fresh and
ISSN 0031–3025 printed/ISSN 1465– 3931 online/00/010021 – 03 © 1999 Royal College of Pathologists of Australasia
22
Pathology (2000), 32, February
HANLEY et al.
Fig. 1 Case 1: liver at postmortem of Case 1 showing extensive red deposites of amyloid in sinusoids with atrophy of hepatocytes (Congo Red, ´ 100).
Fig. 3 Case 2: antral gastric mucosa showing extensive blue/green amyloid deposits in the lamina propria (Sulphated Alcian Blue, ´ 200).
older hemorrhage as well as extensive amyloid deposition demonstrated by Congo red staining. Hematological and biochemical investigations were carried out: hemoglobin 123 g/l, white cell count and platelet count normal, prothrombin ratio normal, APTT 25 s, thrombin clotting time normal, fibrinogen 8.0 g/l (NR 1.5–4 g/l), d-dimer normal, alkaline phosphatas e 176 U/l with otherwise normal liver function tests. Immunoglobulins were normal. Serum electrophoresis showed no paraprotein, but a trace amount of k light chains was detected in the urine. A bone marrow examination showed increased plasma cells (10%), positive by immunofluorescence for k light chains (which are relatively uncommon in primary amyloid1 ). Skeletal radiographs were normal. Further investigation revealed amyloid deposition in the gastro-intestinal tract (via esophageal, gastric (Fig. 3) and duodenal biopsies) and probable cardiac involvement (evidenced by echocardiogram and electrocardiogram). Coagulation screen and factor X assay (145%) were normal. CT scanning showed evidence of intraabdominal lymphadenopathy . In view of the multi-organ involvement and progressive nature of the disease he received high-dose melphalan therapy (200 mg/m2 ) with peripheral blood stem sell rescue. The procedure was complicated by selflimiting gastrointestinal toxicity and an episode of catheter-related sepsis, but he remains well six months post-treatment. Successful DC cardioversion to sinus rhythm has been achieved. There has been complete resolution of his peripheral lymphadenopathy and partial resolution of his hepatomegaly and intra-abdominal lymphadenopath y. However, the alkaline phosphatase remains elevated and his urine shows a trace of Bence Jones protein k type. A repeat bone marrow biopsy showed no increase of plasma cells, although immunophenotyping suggested the presence of a clonal population of plasma cells similar to that found at diagnosis.
DISCUSSION
Fig. 2 Case 1: characteristic apple-green birefringence of amyloid deposits in the liver at postmortem (Congo Red, ´ 100, polarized light).
The diverse clinical manifestations of primary (AL) amyloidosis include hemorrhage and lymphadenopathy. The hemorrhagic tendency is usually due to amyloid infiltration of blood vessels or more rarely specific acquired coagulation deficiencies. Amyloid-associated lymphadenopathy may be isolated7,8 or part of multi-system involvement. 2 The lymph node changes observed in amyloidosis have been described in detail,9 but the specific feature of hemorrhagic lymphadenopathy as a presenting feature of amyloidosis has not been described in the literature. In our two cases this was a prominent clinical manifestation of the disease. The observation of sudden lymph node enlargement followed by spontaneous partial regression is suggestive of recurrent hemorrhage within the amyloid infiltrated node. In both cases there was some delay in diagnosis. Only when the acquired coagulation deficiencies were correctly identified was the diagnosis of AL amyloidosis considered in the first case. In this case the ante-mortem lymph node biopsy revealed such extensive hemorrhagic infarction that any associated amyloid deposition was not detected. Postmortem studies clearly demonstrated the presence of amyloid deposition in lymph nodes. It is likely that the amyloid-associated coagulopathy accentuated the degree of hemorrhage and obscured underlying amyloid deposition in the lymph nodes sampled. Hemorrhagic features within lymph nodes are extremely uncommon. Hemorrhage may occasionally occur in malignant lymphadenopathy in association with tumor necrosis and has been described as a specific feature in spindle-cell tumor (a benign tumor often confused with Kaposi’s sarcoma).10 The treatment of AL amyloidosis remains unsatisfactory. Some patients respond to low-dose chemotherapy, but in general the outlook is poor.11 Encouraging results have recently been reported using high-dose chemotherapy with autologous peripheral blood stem cell support12 and there may be a role for allogeneic bone marrow transplantation. 13 In view of the possibility of such beneficial intensive treatment for patients with AL amyloidosis, early diagnosis
HEMORRHAGIC LYMPHADENOPATHY IN PRIMARY AMYLOIDOSIS
is essential. Due to the wide variety of clinical presentations of AL amyloidosis there may be diagnostic delay. This may have serious implications for the patient as AL amyloidosis is often rapidly progressive. The observation of hemorrhagic changes within lymph node biopsies should prompt the consideration of AL amyloidois as the underlying diagnosis. In the presence of an associated coagulopathy invasive diagnostic biopsy may be hazardous, but an abdominal fat aspiration has been reported as a useful diagnostic tool in this situation.14 AC KN OW LED GEM ENTS The authors thank Joy Monteath and staff (Immunophenotyping Laboratory, Canterbury Health Labs, Christchurch, New Zealand) for diagnostic expertise in the cases presented. Address for correspondence: Dr D. Hanley, Department of Haematology, Canterbury Health Laboratories, PO Box 151, Christchurch, New Zealand. e-mail: [email protected] z
References 1. Falk RH, Comenzo RL, Skinner M. The Systemic Amyloidoses. New Engl J Med 1997; 337: 898–909. 2. Kyle RA, Gertz MA. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol 1995; 32: 45–59. 3. Yood RA, Skinner M, Rubinow A, et al. Bleeding manifestations in 100 patients with amyloidosis. J Am Med Assoc 1983; 249: 1322–4.
23
4. Griepp PR, Kyle RA, Bowie EJW. Factor X deficiency in amyloidosis: a critical review. Am J Hematol 1981; 11: 443–50. 5. McPherson RA, Onstad JW, Ugoretz RJ, Wolf PL. Coagulopathy in amyloidosis: combined deficiencies of factors IX and X. Am J Hematol 1977; 3: 225– 35. 6. Bagley CM Jr, Devita VT Jr, Berard CW, Canellos GP. Advanced lymphosarcoma: intensive cyclical combination chemotherapy with cyclophosphamide, vincristine, and prednisone. Ann Int Med 1974; 76: 227– 34. 7. Spitale LS, Jimenez DB, Montenegro RB. Localised primary amyloidosis of inguinal lymph node with superimposed bone metaplasia. Pathology 1998; 30: 321– 2. 8. Kahn H, Strauchen JA, Gilbert HS, Fuchs A. Immunoglobulin-relate d amyloidosis presenting as recurrent isolated lymph node involvement . Arch Pathol Lab Med 1991; 115: 948–50. 9. Newland JR, Linke RP, Lennert K. Amyloid deposits in lymph nodes: a morphologic and immunohistochemical study. Hum Pathol 1986; 17: 1245– 9. 10. Suster S, Rosai J. Intranodal hemorrhagic spindle-cell tumor with ‘amiathoid’ fibers. Am J Surg Pathol 1989; 13: 347–57. 11. Kyle RA, Gertz MA, Greipp PR, et al. A trial of three regimens for primary amyloidosis: colchicine alone, melphalan and prednisone, and melphalan, prednisone and colchicine. New Engl J Med 1997; 336: 1202– 7. 12. Comenzo RL, Vosburgh E, Falk RH, et al. Dose-intensive melphalan with blood stem cell support for the treatment of AL (amyloid lightchain) amyloidosis: survival and responses in 25 patients. Blood 1998; 91: 3662–70. 13. Gillmore JD, Davies J, Iqbal A, et al. Allogeneic bone marrow transplantation for systemic AL amyloidosis. Br J Haematol 1998; 100: 226–8. 14. Duston MA, Skinner M, Shirahama T, Cohen AS. Diagnosis of amyloidosis by abdominal fat aspiration: analysis of four years experience. Am J Med 1987; 82: 412– 4.