Transcript Clinical Case Conference

Clinical Case Conference
Shivan Mehta, MD
August 11, 2010
Case
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43M h/o Mulitiple Myeloma, chronic kidney
disease presents with 2 weeks of hematochezia.
HPI
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Initially diagnosed with Multiple Myeloma 1 year prior
to presentation. Disease course c/b acute renal failure
requiring short course of dialysis.
Presented to outpatient GI with intermittent
hematochezia x 2 weeks. Reports bright red blood up to
4 times a day on toilet paper and mixed with stool. No
melena. Mild abdominal pain.
ROS significant for 25 lb weight loss, mild abd
cramping and pain, no dizziness/lt headedness/chest
pain/sob
PMH
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PMH: Multiple Myeloma (IgA monoclonal
gammopathy) c/b CKD presenting with renal failure
requiring HD and plasmapheresis. Bone marrow
biopsy/ fat pad neg for amyloid.
PSH: None
Allergies: NKDA
Meds: Velcade/Decadron/Cytoxan (1 course 3 months
prior), Renagel 800mg tid, Nephrocap 1tab daily,
Acyclovir
SH: Works as office manager. Married with no children.
Social Etoh. Denies tobacco/illicits
FH: no malignancy or other GI issues
Physical Exam
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VS- T 97.8, BP 102/63, HR 85, RR 16, 99% RA
Gen- NAD, Ox3, pleasant, comfortable
HEENT- anicteric, pale conjunctivae
CV- RRR, no m/r/g
Chest- CTA b/l
Abd- soft, ND, + BS, mild diffuse TTP
Ext- 1+ lower extremity edema
Rectal- no masses, brown stool with streaks of red
blood
Labs
140| 106| 36
------------------< 82
4.5 | 25 | 3.4
TP 7.4, Alb 3.0
Tbili 1.0, Alk 73
ALT 45, AST 38
8.1
5.8 >-----< 186
24
MCV 88, RDW 16.1
PT 13.2, INR 1.1
PTT 26.4
LDH 90
Differential Diagnosis
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What is your differential diagnosis for
hematochezia in a patient with multiple
myeloma?
Differential Diagnosis
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Ischemic colitis
Infectious colitis
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Diverticulosis
AVM
Upper GI bleed
Neoplasm
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Adenocarcinoma, Lymphoma, Plasmacytoma
Colonic ulcers
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CMV, Salmonella, Shigella, Campylobacter, E. Coli, Entameoba
Medications, Idiopathic
GI amyloid
Inflammatory bowel disease
Hemorrhoids
EGD
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Normal esophagus
Mild antritis-> pathology shows mild lymphocytic infiltrate,
otherwise normal.
Normal duodenum
Colonoscopy
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A large 5cm mass lesion with ulceration was seen in the cecum.
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Small fragment of colonic mucosa within normal limits.
Fragment of fibrinopurulent exudate consistent with nearby ulcer.
Additional areas of ulceration were seen in the left colon.
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Colonic mucosal biopsies with areas of acute inflammation and ulceration,
granulation tissue formation and reactive atypia.
Underlying homogeneous material favor negative for Congo without typical
polarization properties
Repeat Colonoscopy (1 month)
Resolution of large cecal mass with
improvement in ulceration throughout
colon. Only areas of mild erythema.
•Colonic mucosal biopsies with focal acute inflammation and granulation tissue
formation. Submucosal pink amorphous material present which stains with
Congo red but does not show characteristic apple-green birefringence.
•Addendum: A PAS stain was performed and showed no definitive staining in the
amorphous material. A Congo Red stain was repeated and also was negative for
apple-green birefringence. Electon microscopy was performed as an aid to
evaluate the amorphous material and electron microscopy photographs did not
support the presence of amyloid deposition.
Clinical Course
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1 month later, patient admitted with multiple
episodes of hematochezia. Hemoglobin down
to 5.3. Stool studies negative.
CT scan shows:
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Transmural wall thickening with pericolonic fat
stranding involving the rectum and sigmoid . There
is also thickening of the cecum. In addition, this
could also represent hemorrhage into the bowel wall
in the setting of thrombocytopenia.
Repeat Colonoscopy (#3)
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There were innumerable medium-sized punched-out ulcers in
the rectum, rectosigmoid junction, and sigmoid colon.
Appeared to have progressed since prior endoscopy.
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Extensive blood, fibrin, and inflammatory cells, with extremely scant
epithelial cells. Inadequate tissue to evaluate for amyloid or
plasmacytoma.
Repeat EGD/Colonoscopy (#4)
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EGD normal.
Colonoscopy showed similar ulceration throughout
colon with multiple biopsies taken.
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Ischemic changes with ulceration, colonic epithelium. Congo
red stain negative for amyloid.
Differential
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With multiple unrevealing biopsies, what do you
think is still on the differential for colonic
ulcers?
Medication-associated ulcers (Velcade, Acyclovir)
 Ischemic ulcers
 Infectious ulcers
 Amyloid
 Plasmacytoma
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Medication-associated colitis
“Acylovir- induced colitis”
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3 cases of hematochezia within 24 hours
of starting oral acyclovir (guanosine
analog that inhibits viral DNA synthesis)
No other causes was found, and
symptoms resolved with cessation
Colonoscopy showed friable mucosa with
biopsy revealing ulcerated large bowel
Thought to be caused by local irritation to
mucosal surfaces.
Wardle TD et al.
Medication-associated colitis
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Case report of MM patient treated with Velcade (26S
proteosome inhibitor) presenting with abdominal pain,
hematochezia.
Colonoscopy showed multiple colonic ulcers, with
pathology c/w severe interstitial inflammation.
Thought to be iatrogenic colitis 2/2 mucositis.
Sinischalchi et al.
Intestinal Plasmacytoma
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Case reports of plasmacytoma in GI tract
causing bleeding.
Extramedullary plasmacytoma account for 4%
of plasma cell tumors.
Most occur in stomach and 20-30% in small
intestine.
Biopsy shows plasma cell infiltrate, reactive for
CD138 (plasma cell marker).
Hypothesis that extramedullary plasmacytomas
represent low-grade lymphoma of mucosal
lymphoid tissues (MALT) with extensive
plasmacytic differentiation.
Ammar et al. , Carneiro et al
Clinical course
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Patient’s bleeding stabilized and he was
discharged to home with stable hemoglobin.
Patient received Revlamid, Dexamethasone, but
Velcade was stopped due to possible association
with ischemic colitis.
Re-admitted 1 month later with abdominal pain,
diarrhea, hematochezia. Stool studies negative.
EGD/ Flex sig was performed.
EGD/Flex Sig (#5)
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EGD
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Multiple small patchy areas of
irregular erosion in the
incisura and antrum and on
the lesser curvature of the
stomach body.
Normal duodenum.
Flex sig
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Multiple small ulcers in
rectum and circumferential
ulcers in sigmoid. Biopsies
taken.
Pathology
Diagnosis
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Amyloidosis of the Colon
Amyloidosis
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Extracellular deposition of protein fibrils
with a β-sheet fibrillar structure.
Deposits appear homogeneous and
amorphous under light microscope, but
produce a green birefringence when stained
with Congo red and viewed in polarizing
microscope.
Types of Amyloid:
•Primary or light-chain associated (AL)- 15% have MM
•Secondary or reactive (AA)- chronic inflammatory disorders
•Hemodialysis associated (Aβ2M)
•Familial amyloid polyneuropathy (ATTR)
•Senile amyloidosis
Ebert EC et al.
Gastrointestinal Amyloid
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Amyloid may cause GI symptoms extending from
mouth to anus
Amyloid deposition in the GI tract is near universal in
systemic AL amyloidosis, but only 30-60% develop GI
symptoms.
When GI tract is involved, frequency of amyloid in
biopsy specimens area 100% in the duodenum, 95% in
the stomach, 91% in the colorectum, and 72% in the
esophagus. Best in blood vessel wall.
Endoscopically, AL typically forms polypoid
protrusions, while AA amyloidosis is characterized by a
fine granular appearance
Sleisinger and Fordtran., Menke DM et al., Tada S et al., James et al.
GI manifestations
Signs/ symptoms
Amyloid deposition
Blood vessel wall
GI bleeding
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Muscle layers
Dysmotility
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Mucosa
Malabsorption
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Ulcers
Erosions
Polypoid lesions
Submucosal hemorrhage
Dysphagia
Gastroparesis
Constipation,
Pseudo-obstruction
Nausea/vomiting
Weight loss
Diarrhea
Steatorrhea
Protein-losing enteropathy
Ebert et al.
Prognosis/ Treatment
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Median survival for AL amyloidosis less than 2
years, if treated with melphalan and prednisone
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5-year survival improved to 60% with hematopoietic
stem cell transplantation
Treatment of AL involves chemotherapy, while
AA involved treatment of underlying disease.
Follow-up Course
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After amyloid diagnosis, pt given Etoposide,
Cyclophosphamide, Dexamethasone.
2 weeks after EGD/Colonoscopy, pt with fevers,
abdominal pain, hypotension. KUB showed no
perforation.
Patient went to the OR. Ex-lap, lysis of adhesions,
diverting ileostomy, and blow-hole colostomy was
performed, but colectomy deferred due to patient
instability.
Pt with prolonged post-operative hospital course. Restarted on Revlamid. On HD. Just discharged to home.
References
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Ammar T et al. “Primary Antral Duodenal Extramedullary Plasmacytoma Presenting
With Melena” Clinical Gastroenterology and Hepatology. 2010;8:xxxii
Carneiro FP et al. “Extramedullary plasmocytoma associated with a massive deposit of
amyloid in the duodenum.” World J Gastroenterol 2009 July 28; 15(28): 3565-3568
Ebert EC et al. “Gastrointestinal Manifestations of Amyloidosis.” Am J Gastroenterol
2008;103:776–787
James DG et al. “Clinical Recognition of AL Type Amyloidosis of the Luminal
Gastrointestinal Tract” Clinical Gastroenterology and Hepatology. 2007; 5:582–588.
Maza I et al. “Rectal bleeding as a presenting symptom of AL amyloidosis and multiple
myeloma” World J Gastrointest Endosc 2010 January 16; 2(1): 44-46.
Menke DM et al. “Symptomatic gastric amyloidosis in patients with primary systemic
amyloidosis.” Mayo Clin Proc 1993 Aug; 68(8):763-7.
Sinischalchi A et al. “Bortezomib-related colon mucositis in a multiple myeloma patient”
Support Care Cancer (2009) 17:325–327.
Sleisenger and Fordtran’s “Gastrointestinal and Liver Disease” Ninth ed, 2010.
Tada S et al. “Endoscopic and biopsy findings of the upper digestive tract in patients
with amyloidosis.” Gastrointest Endosc 1990 Jan-Feb;36(1):10-4.
Wardle TD et al. “Acyclovir-induced colitis” Aliment Pharmacol Ther. 1997 (11): 415417