Fábián, Katalin

Komaromi T

Kovalszky I

Moldvay, Judit

Papay J

Puskas R

Szállási, Zoltán

Semmelweis Repository

iMedPub Journalshttp://www.imedpub.comTranslational BiomedicineISSN 2172-04792015Vol. 6 No. 2:161© Copyright iMedPub                                                                                                                                                      Find this article in: www.transbiomedicine.comBone Metastasis with Histology Different from The Primary Lung Cancer and The Skin MetastasisMoldvay Judit1,Szállási Zoltán2,3, Puskás Rita4, Komáromi Tamás4, Fábián Katalin4*,Kovalszky Ilona5 Pápay Judit51	 Department	of	Tumor	Biology,	National	Korányi	Institute	of	Pulmonology,	Buda-pest, Hungary 2	 Children’s	 Hospital	 Informatics	 Program	at	 the	 Harvard–Massachusetts	 Institute	of	Technology	Division	of	Health	Sciences	and	Technology,	Harvard	Medical	School,	Boston,	MA,	USA3	 MTA-SE	 NAP,	 Brain	Metastasis	 Research	Group,	Hungarian	Academy	of	 Sciences,	2nd	 Department	 of	 Pathology,	 Semmel-weis	University,	Budapest,	Hungary4	 Department	 of	 Pulmonology,	 Semmel-weis	University,	Budapest,	Hungary5	 1st	 Department	 of	 Pathology,	 Semmel-weis	University,	Budapest,	HungaryCorresponding author: Katalin Fábián drfabian.katalin@gmail.comDepartment	of	Pulmonology,	Semmelweis	University,	1125	Budapest,	Diósárok	u.	1/c,	HungaryTel: +36 30 3885443AbstractIntroduction: It	has	already	been	reported	in	many	types	of	malignant	tumors	that	a	solid	metastasis	can	have	a	different	histology	and	more	aggressive	state	than	the	primary	tumor.	Case presentation: We	 report	 the	 case	 of	 a	 60-year-old	 smoker	 woman	 who	presented	with	bone	metastasis	that	histologically	proved	to	be	an	adenocarcinoma.	Bronchoscopy	revealed	a	squamous	cell	 lung	cancer	that	–	despite	the	different	histology	–	was	regarded	as	the	primary	tumor.	Two	weeks	later	a	rapidly	growing	skin	tumor	developed	that	was	also	a	squamous	cell	carcinoma,	and	was	regarded	as	the	distant	metastasis	of	the	endobronchial	cancer.	Conclusions: In	lung	cancer	it	is	important	not	to	exclude	the	possibility	of	tumor	dissemination	 even	 if	 the	 suspected	 primary	 tumor	 and	 the	 distant	metastasis	have	different	histologies.	Keywords: Lung	cancer,	Different	histology,	Metastasis,	Tumor	heterogeneityBackgroundIt	is	well	known	that	a	metastasis	can	have	a	different	histology	and	more	aggressive	state	than	the	primary	tumor	[1,2].Case presentationA	 60-year-old	 heavy	 smoker	 female	 (pack-year	 index:	 38)	 was	admitted	to	the	Department	of	Pulmonology	of	the	Semmelweis	University	 in	 June	 2013,	 after	 surgery	 because	 of	 pathologic	fracture	 due	 to	 right	 pelvic	 lytic	 metastasis.	 Histologically,	the	 pelvic	 tumor	 mass	 proved	 to	 be	 a	 poorly	 differentiated	adenocarcinoma	 with	 codon	 12	 point	 mutation	 of	 the	 KRAS	gene	 (glycine	 (GGT)	 to	 valine	 (GTT)	 conversion)	 characteristic	for	 smoking-related	 genetic	 changes.	 The	 method	 used	 for	KRAS	 mutation	 analysis	 has	 already	 been	 described	 in	 our	previous	work	by	Cserepes	et	al.	[3].	Bronchoscopy	revealed	an	endobronchially	 visible	 tumor	 in	 the	 right	 lower	 lobe	bronchus	that	was	diagnosed	histologically	as	a	TTF-1	(thyroid	transcription	factor-1)	 negative	 and	 p63	 positive	 squamous	 cell	 carcinoma,	and	 was	 regarded	 as	 the	 primary	 tumor.	 Thoracic	 CT	 showed	paratracheal	lymph	node	enlargement	and	a	small,	lobular	right	upper	 lobe	nodule	both	regarded	as	metastases.	Abdominal	CT	scan	 showed	 enlarged	 left	 adrenal	 gland	 referring	 to	 adrenal	metastasis.	 Two	 weeks	 after	 her	 admission,	 rapidly	 growing	multiple	cystic	subcutaneous	nodules	with	inflammatory	changes	developed	on	 the	 chest	wall	 in	 the	 left	 axillary	 line.	 Aspiration	cytology	showed	squamous	cell	carcinoma	that	was	regarded	as	the	distant	metastasis	of	the	right	central	lung	cancer.	During	her	hospitalization	pathologic	fracture	of	the	left	humerus	occurred.	The	 general	 condition	 of	 the	 patient	 deteriorated	 rapidly	 and	she	died	5	weeks	after	her	admission	even	without	having	 the	opportunity	 to	 receive	 palliative	 oncotherapy.	 In	 summary,	 in	this	 patient	 both	 the	 primary	 tumor	 and	 the	 subcutaneous	metastases	were	squamous	cell	carcinomas;	however,	the	pelvic	bone	 metastasis	 proved	 to	 be	 an	 anaplastic	 adenocarcinoma.	Neither	thoracic	CT	nor	bronchoscopy	showed	any	other	 lesion	that	 could	 have	 been	 regarded	 as	 synchronous	 primary	 lung	cancer	or	other	primary	tumor,	such	as	thyroid	or	breast	cancer.	Moreover,	abdominal	CT	did	not	show	other	 lesion	referring	to	2© Copyright iMedPub                                                                                                                                                                            Find this article in: www.transbiomedicine.comARCHIVOS DE MEDICINAISSN 1698-94652015Vol. 6 No. 2:16Translational BiomedicineISSN 2172-0479extrathoracic	primary	tumor	but	only	adrenal	metastasis,	typical	metastatic	site	of	lung	cancer.		DiscussionIn	 the	 presented	 case	 we	 might	 speculate	 that	 the	 right	 lower	lobe	 endobronchial	 tumor	 contained	 adenosquamous	 elements,	and	during	the	metastatic	process	a	tumor	cell	selection	occurred	resulting	 in	different	histology	 from	 the	primary	 lung	 cancer.	 This	is	 in	accordance	with	the	concept	of	tumor	cell	heterogeneity,	 i.e.	highly	metastatic	cells	are	present	as	a	sub-population	in	a	primary	tumor.	It	is	well	known	that	there	are	different	mechanisms	of	clonal	variation	 including	 clonal	 selection,	 parallel	 evolution,	 dynamic	heterogeneity,	 clonal	 dominance	 and	 stem	 cell	 expansion	 [4].	 In	lung	adenocarcinoma,	the	prognostic	significance	of	KRAS	mutation	has	 already	 been	 documented	 [5].	 The	 correlation	 between	primary	 tumor	and	bone	metastasis	 in	non-small	 cell	 lung	 cancer	was	 investigated	 by	 Badalian	 et	 al,	who	 demonstrated	 that	 KRAS	mutational	status	of	the	primary	tumor	did	not	predict	the	status	of	the	bone	metastatic	tissue,	since	they	had	observed	both	emergence	of	mutant	 clones	 in	metastases	 from	wild-type	 primary	 tumors	and	loss	of	mutant	clones	in	metastases	from	mutant	primaries	in	addition	to	the	maintained	mutant	status	[6].	Skin	 metastases	 from	 lung	 cancer	 are	 rare	 with	 a	 reported	incidence	of	1-2%	[7].	They	are	more	frequent	 in	patients	aged	over	40	years,	and	are	associated	with	a	particularly	aggressive	biological	behavior	[8].	In	our	patient	active	oncotherapy,	which	could	 have	 contributed	 to	 an	 artificial	 selection	 pressure	 for	clonal	 divergence	 or	 stem	 cell	 expansion	 was	 not	 possible	 to	imply,	therefore,	this	case	might	prove	that	even	in	the	absence	of	therapeutic	intervention	histological	difference	between	primary	tumor	and	metastasis	can	be	observed.							ConclusionIn	our	case,	multiple	distant	metastases	with	different	histology	could	 be	 demonstrated.	 The	 skin	 involvement	 had	 the	 same	squamous	 cell	 carcinoma	histology	as	 the	primary	 lung	 cancer,	while	the	bone	metastasis	was	found	to	be	an	adenocarcinoma	with	a	molecular	 feature	 that	might	be	 regarded	as	one	of	 the	most	aggressive	ones	in	the	adenocarcinoma	subgroup.	Competing InterestsAuthors	disclose	no	conflict	of	interest.3ARCHIVOS DE MEDICINAISSN 1698-94652015Vol. 6 No. 2:16Translational BiomedicineISSN 2172-0479© Copyright iMedPub                                                                                                                                                                            Find this article in: www.transbiomedicine.comReferences1 de	 Bruin	 EC,	McGranahan	 N,	Mitter	 R,	 Salm	M,	Wedge	 DC,	 et	 al.	(2014)	Spatial	and	temporal	diversity	in	genomic	instability	processes	defines	lung	cancer	evolution.	Science	346:	251-256.2 Yokota	 J	 (2000)	 Tumor	progression	and	metastasis.	 Carcinogenesis	21:	497-503.3 Cserepes	M,	 Ostoros	 G,	 Lohinai	 Z,	 Raso	 E,	 Barbai	 T,	 et	 al.	 (2014)	Subtype-specific	KRAS	mutations	in	advanced	lung	adenocarcinoma:	a	 retrospective	 study	 of	 patients	 treated	 with	 platinum-based	chemotherapy.	Eur	J	Cancer	50:	1819-1828.	4 Talmadge	 JE	 (2007)	 Clonal	 Selection	 of	Metastasis	 within	 the	 Life	History	of	a	Tumor.	Cancer	Res	67:	11471.	5 Rodenhuis	S,	Slebos	RJ	 (1992)	Clinical	significance	of	ras	oncogene	activation	in	human	lung	cancer.	Cancer	Res	52:	2665s-2669s.6	 Badalian	G,	Barbai	T,	Rásó	E,	Derecskei	K,	Szendrői	M,	et	al.	(2007)	Phenotype	 of	 bone	 metastases	 of	 non-small	 cell	 lung	 cancer:	epidermal	growth	factor	receptor	expression	and	K-RAS	mutational	status.	Pathol	Oncol	Res	13:	99-104.7	 Mollet	TW,	Garcia	CA,	Koester	G	(2009)	Skin	metastases	from	lung	cancer.	Dermatol	Online	J	15:	1.8	 http://www.dermnetnz.org/lesions/metastasis.html.

Bone Metastasis with Histology Different from The Primary Lung Cancer and The Skin Metastasis

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Bone Metastasis with Histology Different from The Primary Lung Cancer and The Skin Metastasis

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