Unknown Primary Tumors:
Newer Concepts and Approches
“10 years experience of a Comprehensive Cancer Center”
Valerio Ramazzotti S.C. Epidemiologia
Roma 05/03/2010
CANCER OF UNKNOWN PRIMARY SITE
1. biopsy - proven malignancy; 2. histology not consistent with a primary tumor at biopsy site;3. unrevealing history, physical examination and usual examinations4. failure of additional diagnostic studies to identify primary site
Della Porta M.G. Department of Hematology Oncology, University of Pavia Medical School and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
Features:
Carcinoma of Unknown Primary –Diagnosis by Light Microscopy
• Well differentiated adenocarcinoma (60%)• Squamous cell carcinoma (5%)• Poorly differentiated adenoca (15%)• Poorly differentiated carcinoma (20%)
From: Hainsworth J. Sarah Cannon Research Institute1 and Tennessee Oncology, PLLC,2 Nashville, Tennessee, USA
Secondary and unspecified malignant neoplasm of lymph nodes ICD9CM CODE: 196
ICD9CM CODE: 197
Secondary malignant neoplasm of respiratory and digestive systems
ICD9CM CODE: 198
Secondary malignant neoplasm of other specified sites
ICD9CM CODE: 199
Malignant neoplasm without specification of site
It is generally reported that unknown primary tumours account for 5–10% of all neoplasms, and that they tend to have an unfavourable prognosis
Unknown Primary Tumours (ICD-O-9 codes 196–199)
Survival curves for biopsy-proven (n=543) and clinically diagnosed (n=156) unknown primary malignant tumours: Vaud and Neuchatel, Switzerland, 1984–1993 (1.7%; 2.3% of all sites, excluding 173)
From Levi F et al. European Journal of Cancer 38 (2002) 1810–1812
CART generated with the initial split on the presence or absence of liver metastases (default tree) (1000 consecutive patients with UPC)
From: K.R. Hess et al. Clinical Cancer Research, Vol. 5, 3403-3410. 1999
Kaplan-Meier survival curves of the 10 terminal subgroups generated from the default CART analysis
From: K.R. Hess et al. Clinical Cancer Research, Vol. 5, 3403-3410. 1999
ITALY: UNKNOWN PRIMARY TUMOURS (ICD9: 199). HOSPITAL ADMISSIONS BY YEAR
8000
8500
9000
9500
10000
10500
1999 2000 2001 2002 2003 2004 2005
http://www.salute.gov.it/ricoveriOspedalieri/ric_informazioni/sceltadia.jsp
ICD9CM CODE: 199 Malignant neoplasm without specification of site
Unknown Primary Tumours (ICD9 199) N. Hospital Admissions by Year. Italy. Men
5636
5280 52315121
4978 4917 4937
1999 2000 2001 2002 2003 2004 2005
All Malignant Tumours (ICD9 140-208)N. Hospital Admissions by Year. Italy. Men.
340621
329760 330076326715
320467
325198 323797
1999 2000 2001 2002 2003 2004 2005
Unnknown Primary Tumours (ICD9 199) Percents of All MalignantTumours by Year of Hospital Admission.
Italy. Men.
1,65
1,60 1,58 1,57 1,551,51 1,52
1999 2000 2001 2002 2003 2004 2005
http://www.salute.gov.it/ricoveriOspedalieri/ric_informazioni/sceltadia.jsp
ICD9CM CODE: 199 Malignant neoplasm without specification of site
ICD9CM CODE: 140-208 All Malignant Neoplasms
Unknown Primary Tumours (ICD9 199) N. Hospital Admissions by Year. Italy. Women
4541
4281
4131
3981 39964064
3959
1999 2000 2001 2002 2003 2004 2005
All malignant Tumours (ICD9 140-208). N. Hospitals Admissions by Year. Italy. Women.
269116
261682 261277258655
254674258249 257167
1999 2000 2001 2002 2003 2004 2005
Unknown Primary Tumours (ICD 199) Percents of All Malignant Tumours of Hospital Admissions by Year.
Italy. Women. 1,7
1,6
1,61,5
1,6 1,61,5
1999 2000 2001 2002 2003 2004 2005
http://www.salute.gov.it/ricoveriOspedalieri/ric_informazioni/sceltadia.jsp
ICD9CM CODE: 199 Malignant neoplasm without specification of site
ICD9CM CODE: 140-208 All Malignant Neoplasms
Unknow Primary Tumours (ICD9: 199). Hospital Admission by Region. 1999
0 500 1000 1500 2000 2500
VALLE D'AOSTA
BASILICATA
P.A. TRENTO
P.A. BOLZANO
MOLISE
CALABRIA
UMBRIA
ABRUZZO
MARCHE
FRIULI V.G.
LIGURIA
SARDEGNA
CAMPANIA
SICILIA
PUGLIA
PIEMONTE
TOSCANA
VENETO
EMILIA ROMAGNA
LAZIO
LOMBARDIA
Unknown Primary Tumours (ICD9: 199). Hospital Admissions by Region. 2000
0 200 400 600 800 1000 1200 1400 1600 1800 2000
VALLE D'AOSTA
BASILICATA
P.A. BOLZANO
P.A. TRENTO
MOLISE
CALABRIA
UMBRIA
SARDEGNA
ABRUZZO
MARCHE
LIGURIA
FRIULI V.G.
CAMPANIA
SICILIA
PUGLIA
VENETO
LAZIO
PIEMONTE
EMILIA ROMAGNA
TOSCANA
LOMBARDIA
Unknown Primary Tumours (ICD9: 199). Hospital Admissions by Region. 2001
0 200 400 600 800 1000 1200 1400 1600 1800 2000
VALLE D'AOSTA
P.A. TRENTO
P.A. BOLZANO
BASILICATA
MOLISE
CALABRIA
UMBRIA
ABRUZZO
FRIULI V.G.
LIGURIA
SARDEGNA
MARCHE
SICILIA
CAMPANIA
PUGLIA
TOSCANA
VENETO
LAZIO
PIEMONTE
EMILIA ROMAGNA
LOMBARDIA
Unknown Primary Tumours (ICD9: 199). Hospital Admissions by Region. 2002
0 200 400 600 800 1000 1200 1400 1600 1800 2000
VALLE D'AOSTA
BASILICATA
P.A. BOLZANO
P.A. TRENTO
MOLISE
CALABRIA
UMBRIA
ABRUZZO
MARCHE
LIGURIA
FRIULI V.G.
SARDEGNA
CAMPANIA
PUGLIA
SICILIA
VENETO
TOSCANA
EMILIA ROMAGNA
PIEMONTE
LAZIO
LOMBARDIA
http://www.salute.gov.it/ricoveriOspedalieri/ric_informazioni/sceltadia.jsp
ICD9CM CODE: 199 Malignant neoplasm without specification of site
Unknown Primary Tumours (ICD9: 199). Hospital Admissions by Region.
2003
0 200 400 600 800 1000 1200 1400 1600 1800
VALLE D'AOSTA
P.A. TRENTO
BASILICATA
P.A. BOLZANO
CALABRIA
UMBRIA
ABRUZZO
MOLISE
FRIULI V.G.
MARCHE
LIGURIA
CAMPANIA
SARDEGNA
PUGLIA
SICILIA
VENETO
TOSCANA
LAZIO
PIEMONTE
EMILIA ROMAGNA
LOMBARDIA
Unknown Primary Tumours (ICD9: 199). Hospital Admissions by Region.
2004
0 200 400 600 800 1000 1200 1400 1600 1800
VALLE D'AOSTA
BASILICATA
P.A. TRENTO
P.A. BOLZANO
UMBRIA
CALABRIA
MARCHE
MOLISE
FRIULI V.G.
ABRUZZO
CAMPANIA
LIGURIA
SARDEGNA
PUGLIA
SICILIA
VENETO
LAZIO
EMILIA ROMAGNA
PIEMONTE
TOSCANA
LOMBARDIA
Unknown Primary Tumours (ICD9: 199). Hospital Admissions by Region. 2005
0 200 400 600 800 1000 1200 1400 1600 1800
VALLE D'AOSTA
BASILICATA
P.A. TRENTO
P.A. BOLZANO
UMBRIA
CALABRIA
MARCHE
FRIULI V.G.
MOLISE
ABRUZZO
CAMPANIA
SARDEGNA
LIGURIA
SICILIA
PUGLIA
VENETO
LAZIO
PIEMONTE
EMILIA ROMAGNA
TOSCANA
LOMBARDIA
http://www.salute.gov.it/ricoveriOspedalieri/ric_informazioni/sceltadia.jsp
ICD9CM CODE: 199 Malignant neoplasm without specification of site
1999
Regional Hospitals; 500;
45%NCI IRE; 75; 7%
Private Hospitals; 247;
22%
University/IRCCS/
Others; 286; 26%
2000
Regional Hospitals; 386;
45%
NCI IRE; 44; 5%
Private Hospitals; 184;
21%
University/IRCCS/ Others;
249; 29%
2001
Regional Hospitals; 406;
47%
University /IRCCS/
Others; 214; 25%
NCI IRE; 61; 7%
Private Hospitals; 185;
21%
2002
Regional Hospitals; 458;
51%University /IRCCS/
Others; 232; 26%
NCI IRE; 35; 4%
Private Hospitals; 172;
19%
Lazio Region. Unknown Primary Tumours (ICD9 Code 199). N. Admissions by Hospital Typology and Year. (1)
http://www.salute.gov.it/ricoveriOspedalieri/ric_informazioni/sceltadia.jsp
Modificata
ICD9CM CODE: 199 Malignant neoplasm without specification of site
2003
Regional Hospitals; 440;
51%University /IRCCS/
Others; 202; 24%
NCI IRE; 42; 5%
Private Hospitals; 168;
20%
2004
Regional Hospitals; 438;
61%
University /IRCCS/
Others; 151; 21%
NCI IRE; 18; 2%
Private Hospitals; 118;
16%
2005
Regional Hospitals; 407;
57%University/
IRCCS /Others; 155;
21%
NCI IRE; 18; 2%
Private Hospitals; 148;
20%
Lazio Region. Unknown Primary Tumours (ICD9 Code 199). N. Admissions by Hospital Typology and Year. (2)
http://www.salute.gov.it/ricoveriOspedalieri/ric_informazioni/sceltadia.jsp
Modificata
ICD9CM CODE: 199 Malignant neoplasm without specification of site
IRE. UNKNOWN PRIMARY TUMOURS (ICD9 199). N. PATIENTS AND HOSPITAL ADMISSIONS BY AGE CLASSES AND GENDER.
TIME PERIOD 1995-2007
0 0 0 0212
337176
263
173
250
123157
0100200300400500600700
N. Patients (men) N. Admissions(men)
N. Patients(women)
N. Admissions(women)
0-14 15-64 65+
ICD9CM CODE: 199 Malignant neoplasm without specification of site
IRE. UNKNOWN PRIMARY TUMOURS (ICD9 199). N. PATIENTS BY TYPOLOGY OF DRG. TIME PERIOD 1995-2007
21031%
47469%
SURGERY MEDICINE
IRE. UNKNOWN PRIMARY SITE (ICD9 199). N. PATIENTS BY RESIDENCE AREA.TIME PERIOD 1995-2007
Lazio14721%
Rome37155%
Extra Region16624%
ICD9CM CODE: 199 Malignant neoplasm without specification of site
IRE. UNKNOWN PRIMARY TUMOURS (ICD9 199). N. ADMISSIONS BY TYPOLOGY OF DRG. TIME PERIOD
1995-2007
22622%
78178%
SURGERY MEDICINE
IRE. UNKNOWN PRIMARY TUMOURS (ICD9 199). N. ADMISSIONS BY DEPARTMENT. TIME PERIOD 1995-2007
50 45 373
3511 1 14
324371
475 11
451 1 1 5
ICD9CM CODE: 199 Malignant neoplasm without specification of site
IRE. UNKNOWN PRIMARY TUMOURS (ICD9 196-199).
0
50
100
150
200
250
300
1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007
N. PATIENTS: tot. 1671 N. ADMISSIONS: tot. 2059
ICD9CM CODE: 196 Secondary and unspecified malignant neoplasm of lymph nodes ICD9CM CODE: 197 Secondary malignant neoplasm of respiratory and digestive systems ICD9CM CODE: 198 Secondary malignant neoplasm of other specified sites ICD9CM CODE: 199 Malignant neoplasm without specification of site
IRE. UNKNOWN PRIMARY TUMOURS (ICD9 196-199). N. PATIENTS BY ICD9 CODE. TIME PERIOD 1995-2007. WOMEN
206235
135
262
206 222184
221
196 197 198 199
MEN WOMEN
ICD9CM CODE: 196 Secondary and unspecified malignant neoplasm of lymph nodes ICD9CM CODE: 197 Secondary malignant neoplasm of respiratory and digestive systems ICD9CM CODE: 198 Secondary malignant neoplasm of other specified sites ICD9CM CODE: 199 Malignant neoplasm without specification of site
IRE. UNKNOWN PRIMARY TUMOURS (ICD9 196-199). N. ADMISSIONS BY ICD9 CODE AND GENDER. TIME
PERIOD 1995-2007
233 265
155
424
218 257198
309
196 197 198 199
MEN WOMEN
ICD9CM CODE: 196 Secondary and unspecified malignant neoplasm of lymph nodes ICD9CM CODE: 197 Secondary malignant neoplasm of respiratory and digestive systems ICD9CM CODE: 198 Secondary malignant neoplasm of other specified sites ICD9CM CODE: 199 Malignant neoplasm without specification of site
IRE. UNKNOWN PRIMARY TUMOURS (ICD9 CODE 196-199). N. ADMISSIONS
BY TYPOLOGY OF DRG. TIME PERIOD 1995-2007
95646%
110354%
SURGERY MEDICINE
ICD9CM CODE: 196 Secondary and unspecified malignant neoplasm of lymph nodes ICD9CM CODE: 197 Secondary malignant neoplasm of respiratory and digestive systems ICD9CM CODE: 198 Secondary malignant neoplasm of other specified sites ICD9CM CODE: 199 Malignant neoplasm without specification of site
IRE. UNKNOWN PRIMARY TUMOURS (ICD9 CODE 196-199). N. ADMISSIONS BY DEPARTMENT. TIME PERIOD 1995-2007
342
194
74 42
178
25 262
403 406
768 21 11 10 3 1 7
192
2
ICD9CM CODE: 196 Secondary and unspecified malignant neoplasm of lymph nodes ICD9CM CODE: 197 Secondary malignant neoplasm of respiratory and digestive systems ICD9CM CODE: 198 Secondary malignant neoplasm of other specified sites ICD9CM CODE: 199 Malignant neoplasm without specification of site
IRE. UNKNOWN PRIMARY TUMOURS (ICD9 CODE 196-199). PRINCIPAL PROCEDURES FROM HOSPITAL ADMISSIONS (FREQUENCY>9). TIME PERIOD 1995-2007
0 50 100 150 200 250 300
LaparoscopyOther total excision of thymus
ElectrocardiogramPercutaneous abdominal drainageRadical neck dissection, bilateral
Diagnostic ultrasound of abdomen and retroperitoneumColonoscopy
Microscopic examination of specimen Routine chest x-ray, so described
Excision of axillary lymph nodeMagnetic resonance imaging of other and unspecified sites
Excision or destruction of peritoneal tissueOther destruction of lesion of liver
Other chest x-rayRadical excision of other lymph nodes
Closed [percutaneous][needle] biopsy of lungComputerized axial tomography of abdomen
Partial hepatectomyOther
Simple excision of other lymphatic structureMagnetic resonance imaging of brain and brain stem
Computerized axial tomography of thoraxOther excision or destruction of lesion or tissue of brain
Exploratory laparotomyRadical neck dissection, not otherwise specified
Other radiotherapeutic procedureOther local excision of lesion or tissue of lung
Radical groin dissectionBiopsy of lymphatic structure
Excision of deep cervical lymph nodeRadical excision of iliac lymph nodes
Radical excision of skin lesionInjection or infusion of other therapeutic substance
Radical neck dissection, unilateralTranspleural thoracoscopy
Closed (percutaneous) [needle] biopsy of liverRadical excision of axillary lymph nodes
Other computerized axial tomographyInjection of cancer chemotherapeutic substance
CODE: 196 Secondary and unspecified malignant neoplasm of lymph nodes ICD9CM CODE: 197 Secondary malignant neoplaICD9CM sm of respiratory and digestive systems ICD9CM CODE: 198 Secondary malignant neoplasm of other specified sites ICD9CM CODE: 199 Malignant neoplasm without specification of site
IRE. UNKNOWN PRIMARY TUMOURS. FURTHER HOSPITAL ADMISSIONS WITH PRINCIPAL DIAGNOSIS V58 vs ALL UPT
196-199 V58
196-199 V58
IRE. UNKNOWN PRIMARY TUMOURS. HOSPITAL ADMISSIONS. PRINCIPAL DIAGNOSIS V58 vs ALL UPT
78%
22%
196-199 V58
IRE. UNKNOWN PRIMARY TUMOURS. FURTHER HOSPITAL ADMISSIONS: ICD9 CODE V58
ICD9CM CODE: V580 Encounter for radiotherapy ICD9CM CODE: V581 Encounter for antineoplastic chemotherapy and immunotherapy
IRE. UNKNOWN PRIMARY TUMOURS. DISTRIBUTION OF SECONDARY DIAGNOSES IN HOSPITAL ADMISSIONS FOR
ICD9 CODE: V58
19613%
19724%
19816%
19947%
ICD9CM CODE: V580 Encounter for radiotherapy ICD9CM CODE: V581 Encounter for antineoplastic chemotherapy and immunotherapy
Conclusions (1)
For unknown primary tumours, hospital discharge data are crucial in clinical care, especially when they are included in the framework of a hospital-based cancer registry (HCR).
Even though HCR is not suitable to compute population incidence or prevalence data, it is a valid tool for hospital administration.