Dunn, Philip, DO

Pandya, Dhwani, MD

Smith, Stacey, MD, FACP

English

Lehigh Valley Health Network: LVHN Scholarly Works

Lehigh Valley Health NetworkLVHN Scholarly WorksDepartment of MedicineGI Bleed with Pancytopenia - A Rare Case of AMLSubtype Acute Panmyelosis with Mylefibrosis(APMF)Dhwani Pandya MDLehigh Valley Health Network, Dhwani.Pandya@lvhn.orgPhilip Dunn DOLehigh Valley Health Network, Philip.Dunn@lvhn.orgStacey Smith MD, FACPLehigh Valley Health Network, Stacey_J.Smith@lvhn.orgFollow this and additional works at: http://scholarlyworks.lvhn.org/medicinePart of the Medical Sciences CommonsThis Poster is brought to you for free and open access by LVHN Scholarly Works. It has been accepted for inclusion in LVHN Scholarly Works by anauthorized administrator. For more information, please contact LibraryServices@lvhn.org.Published In/Presented AtPandya, D., Dunn, P., Smith, S. (2015, October 2). GI Bleed with Pancytopenia - A Rare Case of AML Subtype Acute Panmyelosis withMylefibrosis (APMF). Poster presented at: PSOH, Lafayette Hill, PA.Department of Internal Medicine, Lehigh Valley Health Network, Allentown, PennsylvaniaDhwani Pandya, MD, Phil Dunn, DO and Stacey Smith, MDBackgroundGI Bleed with Pancytopenia - A Rare Case of AML Subtype Acute Panmyelosis with Mylefibrosis (APMF)References:1	 	Chatterjee,	Tathagata	et	al.	“Acute	Panmyelosis	with	Myelofibrosis	-	A	Rare	Subtype	of	Acute	Myeloid	Leukemia.”	Mediterranean Journal of Hematology and Infectious Diseases	5.1	(2013):	e2013042.	PMC.	Web.	06	July	2015.	2	 	Thiele	J,	Kvasnicka	HM,	Zerhusen	G,	Vardiman	J,	Diehl	V,	Luebbert	M,	Schmitt-Graeff	A.	“Acute	panmyelosis	with	myelofibrosis:	a	clinicopathological	study	on	46	patients	including	histochemistry	of	bone	marrow	biopsies	and	follow-up.”	Ann Hematol.	2004	Aug;	83(8):513-21.	Epub	2004	Jun	2.3	 	Orazi,	A.	“Histoopathology	in	the	diagnosis	and	classification	of	acute	myeloid	leukemia,	myelodysplastic	syndromes,	and	myelodysplastic/myeloproliferative	diseases.”	Pathobiology.	2007;74(2):97-114.© 2015 Lehigh Valley Health Network•	 	Pancytopenia	is	defined	by	a	reduction	in	the	counts	of	RBC,	WBC	and	platelets	with	etiologies	ranging	broadly	from	infectious,	malignant	to	many	others.	•	 	Given	the	decline,	presentation	can	vary	from	anemia,	infection	to	bleeding	diathesis.		•	 	In	cases	of	AML,	as	in	this	case,	presentation	with	such	form	becomes	important	to	distinguish	between	Acute	Megakaryoblastic	Leukemia	(AML-M7),	AML	with	Myelodysplasia	(AML-MRC)	and	the	rare	form	APFM,	given	the	standard	treatment	assigned	to	the	former	two.	Case Presentation•	 	A	63-year-old	obese	Caucasian	male	with	no	significant	past	history	except	for	uncontrolled	Type	2	DM	and	OSA	was	brought	to	the	ER	by	his	daughter	with	a	chief	complaint	of	subjective	fevers,	rigors	and	episodic	dyspnea	over	few	days.	•	 	He	denied	any	recent	infectious	exposure	or	malignant	history,	but	complained	of	constant	fatigue,	lethargy,	unintentional	14	pound	weight	loss	over	3	months	and	lightheadedness.	•	 	Upon	ER	presentation,	he	was	found	to	be	febrile	at	103.2F	with	admission	diagnostic	labs	reflecting	pancytopenia	with	hemoglobin	of	6.7,	white	count	of	2.7	and	platelets	of	45,000.	Physical	exam	was	impressive	for	gross	heme	positive	stools	and	orthostatic	hypotension.	•	 	Pan-scanning	was	non-diagnostic	and	an	upper	and	lower	GI	scope	didn’t	establish	a	clear	source	of	bleeding	except	for	mild	gastritis	with	superficial	antral	and	body	erosions	besides	superficial	ascending	colonic	ulcer.	•	 	Despite	a	broad	array	of	testing	from	an	infectious,	gastrointestinal	and	rheumatologic	standpoint,	no	etiology	was	identified,	but	a	subsequent	bone	marrow	biopsy	illustrated	acute	panmyelosis	with	extensive	fibrosis	with	a	dry	tap	and	negative	JAK2,	V617F	and	CALR	mutation.	•	 	Numerous	left	shift	myeloid	and	erythroid	precursors	were	identified	and	mixed	T	and	B-lymphocytes	with	CD34	positive	T	infiltrate	cells	were	noted.	•	 	Thereafter,	patient	was	being	evaluated	for	potential	allogenic	stem	cell	transplant,	when	he	declined	precipitously	and	transformed	into	acute	myelogenous	leukemia	(AML)	with	blast	crisis,	requiring	immediate	induction	therapy	with	various	complications	leading	to	his	salvage	chemotherapy	and	ultimately	demise	from	septic	shock.	Discussion•	 	Pancytopenia,	as	defined	by	a	reduction	in	number	of	red	and	white	blood	cells	along-with	declined	platelet	count	can	present	as	a	challenge	to	clinicians	given	the	broad	differential	it	encompasses.	In	our	patient,	the	combination	of	high-grade	fever	along-with	hemodynamic	instability	and	heme	positive	stool	raised	strong	suspicion	for	infectious	and/or	gastrointestinal	etiologies.	•	 	Initial	diagnostic	studies	for	blood	and	urine	cultures	were	negative	with	pan-scanning	unimpressive	for	a	focal	infectious	source.	Given	culture	negativity,	infectious	profiles	were	run	–	including	Lyme	disease	profile,	Ehrlicia,	Histolpasma,	Fungal	Antibodies,	CMV,	EBV,	HIV,	Parovirus,	Viral	Hepatitis	and	Babeosis	–	which	resulted	negative.	Biopsies	of	gastric	and	colonic	ulcers	were	non-malignant	and	negative	for	Whipple’s	bacillus.	•	 	After	these	etiologies	were	deemed	negative,	toxic	insults	and	malignant	sources	were	considered,	for	which	the	former	was	negative.	Given	pan-scanning	didn’t	showed	any	focal	malignant	sources	or	osseous	metastatic	lesions,	a	bone	marrow	biopsy	was	performed,	which	showed	APMF	with	immunohistochemical	stain	for	CD20,	CD3,	CD34,	CD117,	CD	71,	CD138	and	cytokeratin	showing	mixed	T	and	B	lymphocytes	favoring	T	infiltrate	CD34	but	negative	for	CD34	blasts.	CD117	and	CD71	showed	early	erythroid	precursors	and	reticulin	showed	extensive	reticular	fibrosis	with	negative	trichrome	stain	besides	iron	staining,	which	was	positive,	affirming	the	diagnosis.	•	 	The	World	Health	Organization	(WHO)	classification	of	tumors	of	the	hematopoetic	tissue	defines	APMF	as	a	rare	subtype	of	AML;	with	APMF	profiled	as	a	hematological	malignancy	associated	with	fibrosis	of	the	bone	marrow,	with	little	or	no	splenomegaly,	and	peripheral	blood	counts	indicative	of	pancytopenia,	few	myeloblasts	(<	5%)	and	shift	to	the	left	with	immature	neutrophils	and	rare	normoblasts.	•	 	Given	the	distinct	nature	of	this	classification,	it	becomes	imperative	to	distinguish	it	from	acute	megakaryoblastic	leukemia	(AML-M7),	Primary	Myelofibrosis	(PMF)	and	AML	with	myelodysplasia	–	as	the	classification	of	these	latter	three	allows	for	honed	in	treatment	and	prognosis.•	 	Given	the	rarity	of	this	pathology,	no	standard	therapy	has	been	established	and	the	disease	has	been	reported	to	have	poor	response	to	chemotherapy	with	strong	probability	of	transition	to	AML	with	blast	crises	on	occasion	with	median	survival	of	9	months.		•	 	In	our	patient,	he	was	initiated	on	the	standard	7+3	induction	therapy	(Cytarabine	plus	Daunorubcin)	and	post-induction	bone	marrow	biopsy	showed	minimal	residual	disease	with	5%	blast.	•	 	Later,	in	a	span	of	five	months,	he	was	placed	on	salvage	chemotherapy	with	azacitadine,	but	with	recurrent	neutropenic	fevers	and	transfusion	dependent	anemia,	he	succumbed	to	septic	shock	–	reflecting	a	protracted	course	of	this	rare	AML	subtype.Figure 1: A pictorial representation of APFM: Classic hypercellular bone marrow with panmyeloid proliferation along-with dyspoietic megakaryocytes, immature myeloid precursors and erythroid precursors. No atypical localization of immature precursors seen with small megakaryocytes noted with hypolobated and nonlobated nuclei and dispersed chromatin. Blasts were seen dispersed as well as in clusters. 

GI Bleed with Pancytopenia - A Rare Case of AML Subtype Acute Panmyelosis with Mylefibrosis (APMF)

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GI Bleed with Pancytopenia - A Rare Case of AML Subtype Acute Panmyelosis with Mylefibrosis (APMF)

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