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CPC

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CPC

  1. 1. A 50 year old male with 2 weeks of back pain Clinical Pathology Conference Lisa L. Willett, MD March 24, 2009
  2. 2. Top Ten Rules of a CPC  The answer is always in the title  The case is always an atypical presentation of a common disease…  Or a classic presentation of an uncommon one  TB is always in the differential  There is always a “golden clue”
  3. 3. Top Ten Rules of a CPC  There is always a “red herring”  You must mention diseases no one has heard of  It’s the discussion that’s important  The medical students are always right  “Don’t be surprised if you get it wrong” C. Glenn Cobbs
  4. 4. Case  50 YOM, back pain x 2 weeks  Sharp, severe, mid-back  Hard to get out of bed, but still ambulatory  No focal neurologic deficits by history
  5. 5. PMH Fatigue/NS ↑ BP, ARF -------- Retroperitoneal Fibrosis Back pain 18 mos 2 weeks
  6. 6. PMH ESRD ----- Renal biopsy: Fatigue/NS Xanthogranulomatous ↑ BP, ARF Pyelonephritis -------- Retroperitoneal Fibrosis Primary Hypogonadism Back pain 18 mos 14 mos 2 weeks
  7. 7. PMH ESRD ----- Renal Renal biopsy: Transplant Fatigue/NS Xanthogranulomatous (CMV +) ↑ BP, ARF Pyelonephritis -------- Nephrectomies Retroperitoneal Fibrosis Primary Hypogonadism Back pain 18 mos 14 mos 6 mos 3 mos 2 weeks
  8. 8. PMH ESRD ----- Renal Renal biopsy: Transplant Xanthogranulomatous (CMV +) Fatigue/NS ↑ BP, ARF Pyelonephritis -------- Nephrectomies Retroperitoneal Fibrosis Primary Hypogonadism Back pain 18 mos 14 mos 6 mos 3 mos 2 weeks
  9. 9. Case  Mycophenolate, prednisone, tacrolimus, labetolol, iron, esomeprazole, valganciclovir, TMP/SMX  Social history: married with kids, employed, no illicit drugs or alcohol abuse  ROS: NS, subjective fevers, leg pain  No SOB, weight loss, UTIs, prostatitis
  10. 10. Physical Exam  100.1 116/77 99 16 97%RA 182lb  Well developed, mild discomfort  Bruits - R carotid, B femoral  GU – tender, enlarged L testicle, no mass, no epididymal tenderness  Thoracic spine tenderness  Neurologically intact
  11. 11. Evaluation Positive Negative  Normocytic anemia  UA (not his kidney)  Not iron deficient  ANA <1:80  Elevated CRP, ESR,  SPEP, UPEP, IFE ferritin, platelets  Anion gap  Calcium 9.8  HIV, TB, CMV neg  CXR
  12. 12. Data  Thoracic MRI  Circumferential intracanalicular lesion, appears epidural, extends a long segment from T1 to T7/8  Compresses thecal sac and cord at T4, T5  Vertebral body enhancement T2, T3, T4, T6, T8, T10, T12  Concerning for metastatic extension and/or lymphoma, or multifocal infection
  13. 13. Data CT chest/abd/pelvis  Diffuse intimal calcification lesion in the thoracic aorta  Stable retroperitoneal stranding  Unchanged sclerotic bone in hemisacrum and very small but enlarged sclerotic lesion R ilium  Bilateral patchy sclerosis of femoral & humeral heads
  14. 14. Confused? Overwhelmed?
  15. 15. Lots of stuff  Retroperitoneal fibrosis  Bone mets – spine, pelvis, proximal girdle  Spinal cord mass? – epidural / extensive  Testicular swelling (mass?)  Acquired primary hypogonadism  Vascular calcifications & bruits  Immunosuppressed, renal transplant
  16. 16. Red Herring v Golden Clue
  17. 17. How did it all begin? ESRD ----- Renal Renal biopsy: Transplant Fatigue/NS Xanthogranulomatous (CMV +) ↑ BP, ARF Pyelonephritis -------- Nephrectomies Retroperitoneal Fibrosis Primary Hypogonadism Back pain 18 mos 14 mos 6 mos 3 mos 2 weeks
  18. 18. What is Retroperitoneal Fibrosis?  Clinicopathologic systemic disease  Sclerotic tissue develops in periaortic and peri-iliac retroperitoneum  Encases structures  In spectrum with chronic aortitis  Lack of diagnostic criteria  Rare  0.1 per 100,000, peak 40-60, male Vaglio, et al, Rheum Dis Clin N Am 2007;33:803-817
  19. 19. Etiology Idiopathic: association with other autoimmune diseases (thyroid, pancreatitis, SLE)  HLA-DRB1*03 – select antigens trigger disease Secondary <1/3 of cases  Medications, malignancies, infections, trauma, radiotherapy, surgery
  20. 20. Despite the name, it’s an inflammatory process  Not a sclerotic reaction to an insult  Inflammatory reaction  Peculiar histopathologic aspects  Lymphocytes, plasma cells, macrophages  Circulating autoantibodies  Acute phase reactants elevated  Polyclonal hypergammaglobulinemia
  21. 21. Retroperitoneal Fibrosis  Firm grayish mass surrounding aorta and iliac arteries  From renal arteries to common iliacs  Fibrous & inflammatory  Fibroblasts, lymphocytes, plasma cells, macrophages, eosinophils
  22. 22. Clinical presentations  Common:  Pain (back, abdominal, flank pain)  Low-grade fever, weight loss, anorexia, fatigue  Moderately frequent  Testicular pain, varicocele  Constipation, nausea, vomiting  DVT, edema  Rare  Polyuria, oliguria, erectile dysfunction
  23. 23. How did it all begin? ESRD ----- Renal Renal biopsy: Transplant Fatigue/NS Xanthogranulomatous (CMV +) ↑ BP, ARF Pyelonephritis -------- Nephrectomies Retroperitoneal Fibrosis Primary Hypogonadism Back pain 18 mos 14 mos 6 mos 3 mos 2 weeks
  24. 24. What is xanthogranulomatous pyelonephritis?  Variant of chronic pyelonephritis  Seen in obstruction from infected renal stone  E. coli, Proteus, Pseudomonas, Strept faecalis, Klebsiella  Massive kidney destruction  Granulomatous tissue with lipid laden macrophages UpToDate
  25. 25. Lots of stuff  Retroperitoneal fibrosis  Bone mets – spine, long bones, pelvis  Spinal cord mass? – epidural / extensive  Testicular lesion (swelling, mass?)  Acquired primary hypogonadism  Vascular calcifications & bruits  Immunosuppressed, renal transplant
  26. 26. How sharp is Occam’s razor?  Idiopathic RPF  Secondary RPF  Testicular pain, varicocele  Long bones, pelvis  Spinal cord lesion  Metastatic infection or  Testicular lesion malignancy  Vascular calcifications  Long bones, pelvis  Primary hypogonadism  Spinal cord lesion  Testicular lesion  ESRD  Vascular calcifications  Primary hypogonadism
  27. 27. How sharp is Occam’s razor?  Idiopathic RPF  Testicular pain, varicocele  Metastatic infection or malignancy  Long bones, pelvis  Spinal cord lesion  Testicular lesion  ESRD  Vascular calcifications  Primary hypogonadism
  28. 28. Spinal Metastasis  After lungs and liver, skeletal system is most often involved  Lung, prostate, breast, hematopoetic, GI tract  20% present with spinal problem  Thoracic spine 60 – 80%  Intradural (intra or extra medullary)  Extradural – 95%  Pure epidural  From the vertebrae -- majority Bartels, Cancer J Clin 2008;58:245-49
  29. 29. - www.aafp.org/afp/20020501/1834_f3.gif
  30. 30. Data  Thoracic MRI  Circumferential intracanalicular lesion, appears epidural, extends a long segment from T1 to T7/8  Compresses thecal sac and cord at T4, T5  Vertebral body enhancement T2, T3, T4, T6, T8, T10, T12  Concerning for metastatic extension and/or lymphoma, or multifocal infection
  31. 31. Option #1  Idiopathic RPF  Metastatic infection or malignancy  Long bones, pelvis  Vertebrae/ spinal lesion  Testicular lesion  ESRD  Vascular calcifications  Primary hypogonadism
  32. 32. Option #1  Idiopathic RPF  Multiple myeloma  Plasmacytoma  Metastatic infection or  Extramedullary malignancy plasmacytoma  Long bones, pelvis  Lymphoma (HD, NHL)  Vertebrae / spinal lesion  Solid tumors  Testicular lesion  Testicular, prostate, renal  Lung, melanoma, others  ESRD  Infections  Vascular calcifications  TB, fungal (histo), bacterial  Primary hypogonadism
  33. 33. Multiple Myeloma  Aberrant production of monoclonal proteins by a neoplastic clone of plasma cells (BM >10% plasma cells)  Mean age = 62  Anemia, hypercalcemia, renal insufficiency, lytic bone lesions  2/3 have bone pain at diagnosis  M-protein - 1% are non-secretors
  34. 34. Multiple Myeloma Variants 1. Myeloma = bone marrow 2. Solitary plasmacytoma of bone = single lesion  no MM in marrow  IFE no M-spike 3. Extramedullary plasmacytoma = plasma cell tumor outside the marrow and bone  Upper respiratory 80%  GI, CNS, thyroid, testes, parotid Kyle, Clin Chem 1994;40/11(B):2154-61
  35. 35. Testicular Plasmacytoma  Rare, incidence 1/1000 testicular tumors  Avg age = 60 yrs  About 50 cases published  Primary or secondary is debated  Number of cases reported of testicular plasmacytoma and concurrent MM or EMP from 1939 to 2002 = 34 cases  Intriguing, but not…not lytic lesions, no M-spike, hypercalcemia Anghel, Am J Hematol 2002;71:98-104 Hou, Ann Hematol 2003;82:518-20
  36. 36. Option #1  Idiopathic RPF  Multiple myeloma  Plasmacytoma  Metastatic infection or  Extramedullary malignancy plasmacytoma  Long bones, pelvis  Lymphoma (HD, NHL)  Vertebrae/spinal lesion  Solid tumors  Testicular lesion  Testicular, prostate, renal  Lung, melanoma, others  ESRD  Infections  Vascular calcifications  TB, fungal (histo), bacterial  Primary hypogonadism
  37. 37. Testicular cancer  Most common ages 15-35, can occur later  Seminomas, non-seminomas (germ)  Mets:  Distant lymph node 15%  Liver 13%  Lung 12%  Kidney 7.5%  Bone 5.5% DiSibio, Arch Pathol Lab Med 2008;132:931-39
  38. 38. Testicular cancer  Case report: 52 yom Leydig to spine*  Usually metastastic to regional lymph nodes, and then to lung, liver, and bone  3 previously reported cases in the literature with spinal mets DiSibio, Arch Pathol Lab Med 2008;132:931-39 *Samoladas, World J Surg Onc 2008;7:75
  39. 39. Option #1  Idiopathic RPF  Multiple myeloma  Plasmacytoma  Metastatic infection or  Extramedullary malignancy plasmacytoma  Long bones, pelvis  Lymphoma (HD, NHL)  Vertebrae/spinal lesion  Solid tumors  Testicular lesion  Testicular, prostate, renal  Lung, melanoma, others  ESRD  Infections  Vascular calcifications  TB, fungal (histo), bacterial  Primary hypogonadism
  40. 40. How sharp is Occam’s razor?  Idiopathic RPF  Secondary RPF  Testicular pain, varicocele  Long bones, pelvis  Spinal cord lesion  Metastatic infection or  Testicular lesion malignancy  Vascular calcifications  Long bones, pelvis  Primary hypogonadism  Spinal cord lesion  Testicular lesion  ESRD  Vascular calcifications  Primary hypogonadism
  41. 41. How sharp is Occam’s razor?  Secondary RPF  Long bones, pelvis  Spinal cord lesion  Testicular lesion  Vascular calcifications  Primary hypogonadism
  42. 42. Secondary RPF Drugs Methysergide, pergolide, bromocriptine, ergotamine, methyldopa, hydralazine, analgesics, beta-blockers Cancer Carcinoid, Hodgkin’s, NHL, sarcomas carcinomas of colon, breast prostate, breast, stomach Infections TB, histoplasmosis, actinomycosis Radiotherapy Testicular seminoma, colon or pancreatic carcinoma Surgery Lymphadenectomy, colectomy, hysterectomy, AAA Others Histiocytosis, Erdheim-Chester disease, amyloidosis, trauma, barium enema Up To Date; Vaglio, Lancet 2006
  43. 43. Carcinoid Tumors  Neuroendocrine tumors  Peak incidence age 50 - 70  Secretion of vasoactive peptides depends on site of origin  Any location in body  GI tract 65%  Bronchopulmonary tract 25%
  44. 44. Embryologic Origins  Foregut  Lungs, bronchi  Stomach  Midgut  Small intestines  Appendix  Proximal colon  Hindgut (asymptomatic)  Distal colon, rectum  GU http://www.embryology.ch/anglais/rrespiratory/korperhohlen01.html
  45. 45. Carcinoid Tumors, Syndrome  Flushing, diarrhea, wheezing  Serotonin (5-HT)  Release into systemic circulation (lung, liver mets)  Dx:  urinary 5-HIAA, breakdown product of serotonin (sens 35%, spec 100%)  platelet serotonin level (sens 68%) Zuetenhorst, The Oncologist 2005;10:123-31
  46. 46. Carcinoid and Bone Mets  Mets: regional lymph nodes, liver, skin, bone  Skeletal metastases 10%  Axial skeleton  More often from bronchial or hindgut  Hindgut: rarely cause carcinoid syndrome, even when metastatic  Carcinoid of testis (hindgut): primary or metastatic Stroosma, BJU Int 2008101:1101 Auetenhorst, Nucl Med Commun 2002;23:735-41 Shimura, Nippon Hinyokika 1991;82(7):1157-60
  47. 47. Bone Metastases in Carcinoid Tumors: Clinical Features, Imaging Characteristics  Retrospective study of 90 patients  11 had bone metastases (12%)  All were midgut  No hypercalcemia  Blastic and lytic lesions  10/11 had liver mets  11/11 had carcinoid syndrome Meijer, J Nuclear Medicine 2003
  48. 48. Carcinoid tumors of the testis  1930 to 2006, 61 cases published  44 primary  6 metastatic to testis  12 arose in testicular teratoma  Age 38-61  Symptoms – painless mass (80%), scrotal pain (16%)  One had cervical and thoracic vertebral mets, none had long bones or pelvis like our patient Stroosma, BJU 2008
  49. 49. Secondary RPF Drugs Methysergide, pergolide, bromocriptine, ergotamine, methyldopa, hydralazine, analgesics, beta-blockers Cancer Carcinoid, Hodgkin’s, NHL, sarcomas carcinomas of colon, breast prostate, breast, stomach Infections TB, histoplasmosis, actinomycosis Radiotherapy Testicular seminoma, colon or pancreatic carcinoma Surgery Lymphadenectomy, colectomy, hysterectomy, AAA Others Histiocytosis, Erdheim-Chester disease, amyloidosis, trauma, barium enema Up To Date; Vaglio, Lancet 2006
  50. 50. Sarcomas  Limb, limb girdle, or within abdomen  Retroperitoneal 20%  Painless, gradually enlarging mass  Growth rate variable – 50 different types  Bloodstream metastases  Lung most common  Bone, lymph nodes, liver, subcutan tissues Clark, et al, NEJM 2005;353:701-11
  51. 51. Retroperitoneal Sarcomas  Liposarcoma most common  Retroperitoneal tumors can become huge  Insidious course  Expand spherically and along tissue planes  Centrifugal growth creates false capsule
  52. 52. Skeletal Metastases from Soft- Tissue Sarcomas  Retrospective study of 277 patients from 1975 to 1995  10% skeletal metastases  Liposarcoma accounted for 4% of all  All osteolytic on radiographs  Mean interval 18.6 mos (0-66)  Multiple bone mets, involved spine and legs  NONE had bilat femoral and humeral heads Yoshikawa, J Bone Joint Surg 1997;79-B:548-52
  53. 53. How sharp is Occam’s razor?  Idiopathic RPF  Secondary RPF  Testicular pain, varicocele  Long bones, pelvis  Spinal cord lesion  Metastatic infection or  Testicular lesion malignancy  Vascular calcifications  Long bones, pelvis  Primary hypogonadism  Spinal cord lesion  Testicular lesion  ESRD  Vascular calcifications  Primary hypogonadism
  54. 54. Final differential diagnoses  Idiopathic RPF  Secondary RPF  Metastatic testicular  Carcinoid tumor from cancer hindgut (non secretory)  Leydig cell  Testicular primary with metastatic spine  Retroperitoneal sarcoma  Liposarcoma
  55. 55. Final differential diagnoses  Idiopathic RPF  Secondary RPF  Metastatic testicular  Carcinoid tumor from cancer hindgut (non secretory)  Leydig cell  Testicular primary with metastatic spine  Retroperitoneal sarcoma  Liposarcoma
  56. 56. Data CT chest/abd/pelvis  Diffuse intimal calcification lesion in the thoracic aorta  Stable retroperitoneal stranding  Unchanged sclerotic bone in hemisacrum and very small but enlarged sclerotic lesion R ilium  Bilateral patchy sclerosis of femoral & humeral heads
  57. 57. Secondary RPF Drugs Methysergide, pergolide, bromocriptine, ergotamine, methyldopa, hydralazine, analgesics, beta-blockers Cancer Carcinoid, Hodgkin’s, NHL, sarcomas carcinomas of colon, breast prostate, breast, stomach Infections TB, histoplasmosis, actinomycosis Radiotherapy Testicular seminoma, colon or pancreatic carcinoma Surgery Lymphadenectomy, colectomy, hysterectomy, AAA Others Histiocytosis, Erdheim-Chester disease, amyloidosis, trauma, barium enema Up To Date; Vaglio, Lancet 2006
  58. 58. Histiocytosis  Langerhans’-cell Histiocytosis  Neoplasm of dendritic cell origin  Childhood illness  Pituitary dysfunction  Diabetes insipidus  Lytic bone lesions
  59. 59. Erdheim-Chester Disease  Non-Langerhans cell histiocytosis  < 100 reports in the literature  Jacob Erdheim, William Chester 1930  Infiltrative process of bone marrow and multiple organ systems  Unique staining pattern (CD68+, S-100 neg)  Males, 40 – 50s  Median survival 32 months
  60. 60. Erdheim – Chester Disease  Infiltration begins in the bones  Bilateral symmetric foci of sclerosis in appendicular long bones  Metaphysis and diaphysis  11 patients, 100% long bones involved  Spares the axial skeleton, usually  KNEE PAIN is classic
  61. 61. http://radiology.rsnajnls.org/cgi/content/figsonly/238/2/632
  62. 62. Bone patterns  Typical diffuse skeletal involvement  Symmetric sclerosis of long bones  Pseudotumors present like a soft tissue mass  Case report of thoracic spine in 55 yom (and with sclerotic lesion in left ilium) Klieger, AJR 2002;178:429-32
  63. 63. Extraosseous ECD  Occurs in 60% of patients  Classic: diabetes insipidus, B exophthalmos  Sinus mass  Retroperitoneum  Periaortic/perivascular tissues  Lungs  Heart
  64. 64. Retroperitoneal Erdheim – Chester Disease  Retroperitoneal infiltration confused with RPF  Extensive perinephric involvement pathognomonic  Histology: xanthomatous or xanthogranulomatous infiltration with lipid laden macrophages or histiocytes, surrounded by fibrosis
  65. 65. Retroperitoneal Erdheim – Chester Disease  Retroperitoneal infiltration confused with RPF  Extensive perinephric involvement pathognomonic  Histology: xanthomatous or xanthogranulomatous infiltration with lipid laden macrophages or histiocytes, surrounded by fibrosis
  66. 66. But wait, there’s more…  Perivascular infiltrates may cause vessel stenosis or occlusion  “Coated aorta” circumferential sheathing
  67. 67. But wait, there’s more!! Erdheim-Chester disease: case report with multisystemic manifestations including testes, thyroid, and lymph nodes, and a review of literature  3 cases of primary hypogonadism  Testicular tubular atrophy (granulomatous orchitis) Sheu, et al, J Clin Pathol 2004;57:1225-28
  68. 68. How sharp is Occam’s razor?  Secondary RPF  Long bones, pelvis  Spinal cord lesion  Testicular lesion  Vascular calcifications  Primary hypogonadism  ROS: leg pain located above the knees  Xanthogranulomatous pyelonephritis biopsy
  69. 69. Final Diagnosis: Erdheim-Chester Disease Procedure: biopsy

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