cpc

A 50 year old male with 2 weeks of back pain

Clinical Pathology Conference

Lisa L. Willett, MD

March 24, 2009

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”

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

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

Back pain

2 weeks18 mos

Fatigue/NS↑ BP, ARF

--------Retroperitoneal

Fibrosis

PMH

Back pain

2 weeks18 mos



Fibrosis

14 mos

ESRD-----

Renal biopsy: Xanthogranulomatous

Pyelonephritis

Primary Hypogonadism

PMH

Back pain

2 weeks18 mos



Fibrosis

14 mos

ESRD-----


Pyelonephritis


6 mos

Nephrectomies

3 mos

Renal Transplant(CMV +)

PMH

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

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

Evaluation

Positive Normocytic anemia

Not iron deficient

Elevated CRP, ESR, ferritin, platelets

Negative UA (not his kidney) ANA <1:80 SPEP, UPEP, IFE Anion gap Calcium 9.8 HIV, TB, CMV neg CXR

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

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

Confused?Overwhelmed?

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

Red Herring v Golden Clue

Back pain

2 weeks18 mos



Fibrosis

14 mos

ESRD-----


Pyelonephritis


6 mos

Nephrectomies

3 mos


How did it all begin?

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

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

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

Retroperitoneal Fibrosis

Firm grayish mass surrounding aorta and iliac arteries From renal arteries to

common iliacs

Fibrous & inflammatory Fibroblasts, lymphocytes,

plasma cells, macrophages, eosinophils

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

Back pain

2 weeks18 mos



Fibrosis

14 mos

ESRD-----


Pyelonephritis


6 mos

Nephrectomies

3 mos


How did it all begin?

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

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

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

Secondary RPF Long bones, pelvis Spinal cord lesion Testicular lesion Vascular calcifications Primary hypogonadism

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

- www.aafp.org/afp/20020501/1834_f3.gif

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

Option #1

Idiopathic RPF

Metastatic infection or malignancy Long bones, pelvis Vertebrae/ spinal lesion Testicular lesion


Option #1

Idiopathic RPF

Metastatic infection or malignancy Long bones, pelvis Vertebrae / spinal lesion Testicular lesion


Multiple myeloma Plasmacytoma Extramedullary

plasmacytoma Lymphoma (HD, NHL) Solid tumors

Testicular, prostate, renal Lung, melanoma, others

Infections TB, fungal (histo), bacterial

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

Multiple Myeloma Variants

1. Myeloma = bone marrow2. 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

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

Option #1

Idiopathic RPF

Metastatic infection or malignancy Long bones, pelvis Vertebrae/spinal lesion Testicular lesion






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

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

Option #1

Idiopathic RPF

Metastatic infection or malignancy Long bones, pelvis Vertebrae/spinal lesion Testicular lesion






How sharp is Occam’s razor? Secondary RPF Long bones, pelvis Spinal cord lesion Testicular lesion Vascular calcifications Primary hypogonadism

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

Secondary RPF

Up To Date; Vaglio, Lancet 2006

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%

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

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

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 2008101:1101Auetenhorst, Nucl Med Commun 2002;23:735-41Shimura, Nippon Hinyokika 1991;82(7):1157-60

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

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








Secondary RPF


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

Retroperitoneal Sarcomas

Liposarcoma most common Retroperitoneal tumors can become huge Insidious course Expand spherically and along tissue planes

Centrifugal growth creates false capsule

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

Final differential diagnoses

Idiopathic RPF Metastatic testicular

cancer Leydig cell

Secondary RPF Carcinoid tumor from

hindgut (non secretory) Testicular primary with

metastatic spine

Retroperitoneal sarcoma Liposarcoma

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








Secondary RPF


Histiocytosis

Langerhans’-cell Histiocytosis Neoplasm of dendritic cell origin Childhood illness Pituitary dysfunction

Diabetes insipidus Lytic bone lesions

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

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

http://radiology.rsnajnls.org/cgi/content/figsonly/238/2/632

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

Extraosseous ECD

Occurs in 60% of patients

Classic: diabetes insipidus, B exophthalmos Sinus mass Retroperitoneum Periaortic/perivascular tissues Lungs Heart

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

But wait, there’s more…

Perivascular infiltrates may cause vessel stenosis or occlusion

“Coated aorta” circumferential sheathing

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

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

Final Diagnosis:Erdheim-Chester

Disease

Procedure: biopsy

cpc

Documents

mos3 mos

pain x

weeks sharp

pmh fatiguens bp

renalrenal biopsy

case mycophenolate

classic presentation

atypical presentation