Is It Really an Unknown Primary?

Transcription

1 ???? Is It Really an Unknown Primary? Presentation developed by April Fritz, RHIT, CTR What Is an Unknown Primary? A histologically-proven cancer in a metastatic site, for which its point of origin cannot be determined Other names Unknown Primary Unk 1 Cancer of Unknown Primary (CUP) Occult Primary Cancer Cancer of Unknown Origin (CUO) 2 SEER Site Group: Ill-defined and Unknown C760-C768*, C809* C420-C424* C770-C779* * Except (Mesothelioma), 9140 (Kaposi sarcoma), (Hematopoietic/lymphoid) Histologies , , 9950, , , 9970, 9971, 9975, 9980, , 9989, 9991,

2 Histologies Grouped as Ill-Defined Mast cell tumors Histiocytic, Langerhans, Immunoproliferative diseases Polycythemia vera Myeloproliferative diseases (ET, Myelosclerosis) Genetic rearrangements Lymphoproliferative disorder Post-transpl lymphoprolif disorder Myeloproliferative disease Refractory anemia RAEB, Other RA Myelodysplastic syndrome, NOS Refractory neutropenia Refractory thrombocytopenia 4 Epidemiology Incidence Estimated 34,170 new cases % 5% of all cancers in US Becoming less common due to better Dx methods Primary later identified in < 30% M : F ratio equal Average age at Dx: 60 Outcomes Tend to be aggressive More difficult to treat because primary unknown Prognosis Lymph node mets only: 6-9 months Extranodal mets: 2-4 months 5-yr overall survival: 5-10% 5 Symptoms Based on site of metastases and possible site of origin Firm, swollen lymph nodes that are not painful Palpable mass in abdomen or mass that causes a feeling of fullness after a small meal Shortness of breath Pain in chest or abdomen Pain in bones Skin tumors Fatigue or weakness Lack of appetite or unexplained weight loss 6 2

3 Workup of Unknown Primary Thorough H&P Blood and biochemistry tests Immunohistochemistry (CK7, CK20) Common (non-specific) tumor markers: CEA, AFP, CA19-9, CA-125, PSA Biopsy w/wo electron microscopy or flow cytometry FNA, core needle, incisional biopsy Excisional biopsy Thoracentesis, paracentesis Bone marrow aspiration and biopsy Imaging X-rays, CT +/- PET, MRI Ultrasound Mammography Endoscopy Molecular/gene profiling (under investigation) 7 Remember Little tissue little diagnosis Think not However, patterns of mets tend to be significantly different from expected or usual presentation for a primary site 8 Major Histologic Categories Adenocarcinomas (well/mod diff) (60%) Likely sites: pancreas, gallbladder, biliary tract, lung, kidney Less likely sites: breast, prostate, stomach, liver or colon Poorly diff/undiff carcinoma (29%) Not enough detail to identify specific cell type Poorly diff/undiff malignant neoplasm (5%) Definitely cancer, but so abnormal the cell type cannot be determined May be lymphoma, sarcoma or melanoma Squamous cell cancer (5%) Epithelial cells (skin, linings of some organs) Neuroendocrine carcinoma (1%) Scattered in organs such as esophagus, stomach, pancreas, intestines and lungs 9 3

4 Immunohistochemistry CK7 and CK20 CK7 found in lung, ovary, endometrium, thyroid, breast CK20 found in GI, urothelium, Merkel cell carcinomas Primary Markers Possible Primary Site Additional Markers CK7- / CK20+ Colorectal, Merkel cell CEA, CDX-2 CK7+ / CK20- CK7+ / CK20+ CK7- / CK20- Lung, breast, thyroid, endometrium, cervix, pancreatic carcinomas and cholangiocarcinoma Urothelial, ovary, and pancreas cancers and cholangiocarcinoma Hepatocellular, renal cell, prostate, squamous cell TTF-1, ER, PR, GCDFP-15, CK19 Urothelin, WT-1 Hep Par-1, PSA 10 Further Immunohistochemistry Markers 11 Site-Specific Markers AFP (germ cell tumors, hepatoma) Chromogranin A (neuroendocrine tumors) ER, PR, HER2 (breast) HCG (germ cell tumors) Keratin (epithelial tumors) Leukocyte common antigen (LCA) PSA (prostate) S-100 (melanoma) Synaptophysin (neuroendocrine tumors) Thyroid transcription factor (TTF-1) (lung, thyroid) 12 4

5 Default Primary Site Codes for Certain Histologies Histology Group ICD-O-3 Code(s) Default Code for Unk Prim Melanoma C44.9 Sarcoma C49.9 Meningioma C70.9 Cholangiocarcinoma C24.0 Hepatocellular carcinoma C22.0 Retinoblastoma C69.2 Lymphoma C77.9 Kaposi sarcoma 9140 C44.9 Hematopoietic (most) C Guidelines for Assigning Primary Site Code as specifically as possible Non-specific sites other than C76, C80 C14.0 Pharynx, NOS C14.8 Overlapping lesion of lip oral cavity and pharynx C24.1 Pancreatobiliary, NOS C26.9 Gastrointestinal tract, NOS C39.9 Ill-defined sites within respiratory system C57.9 Female genital tract, NOS C63.9 Male genital organs, NOS C68.9 Urinary system, NOS C75.9 Endocrine gland, NOS 14 Presentation vs. Possible Primary Adenoca w/ pos axillary and mediastinal nodes in female possible breast Breast MRI finds tumor in 50-70% Also adenoca in SC nodes, chest, peritoneum, retroperitoneum, liver, bone brain Female with mediastinal, inguinal, peritoneal, chest, retroperitoneal mets possible ovary CA-125 testing Adenocarcinoma in mediastinal nodes possible extragonadal germ cell tumor Also retroperitoneal mass in male < 65 y.o. AFP and HCG testing Men > 40 y.o. with adenoca except in liver or brain possible prostate PSA testing 15 Also men any age with bone mets or carcinomatosis 5

6 Presentation vs. Possible Primary Metastatic squamous cell carcinoma In supraclavicular, head and neck, axilla possible head and neck primary FNA, complete endoscopies, HPV testing In inguinal nodes possible cervix (females) or anus CT abdomen/pelvis, gyn consult, anal endoscopy In mediastinum possible non-small cell lung cancer Ascites possible GI or ovary primary Brain metastases possible lung, breast kidney Bone metastases possible prostate, breast, lung, kidney, thyroid 16 Other Pointers to Possible Primary Site Lung mets Tend to be from primaries above the diaphragm Liver mets Tend to be from primaries below the diaphragm 17 Common Sites of Metastasis Bladder Breast Colorectal Kidney Lung Melanoma Ovary Pancreas Prostate Stomach Thyroid Uterus Bone, liver, lung Bone, brain, liver, lung Liver, lung, peritoneum Adrenal gland, bone, brain, liver, lung Adrenal gland, bone, brain, liver, other lung Bone, brain, liver, lung, skin/muscle Liver, lung, peritoneum Liver, lung, peritoneum Adrenal gland, bone, liver, lung Liver, lung, peritoneum Bone, liver, lung Bone, liver, lung, peritoneum, vagina 18 6

7 Unfavorable Prognostic Factors Male gender Poor performance status Metastases in multiple organs Non-papillary malignant ascites Peritoneal metastases Multiple cerebral metastases Adenocarcinoma with multiple lung/pleural or bone lesions 19 Favorable Prognostic Factors PD carcinoma with midline distribution Women with papillary adenoca of peritoneal cavity Women with only axillary mets Squamous cell carcinoma in cervical nodes Isolated inguinal adenopathy (SqCC) PD neuroendocrine carcinoma Men with blastic bone mets and elevated PSA Single, small potentially resectable tumors 20 Of the 30% Found During Workup Lung 15% Pancreas 13% Sarcomas 6-8% Melanomas 6-8% Lymphomas 6-8% Colon-rectum 6% Kidney 5% Breast 4% Stomach 4% Ovary 3% Liver 3% Esophagus 3% Prostate 2% All others 22% 21 7

8 Staging Summary Stage 2000 Other and Ill-Defined Sites, Unknown Primary Site Code 9 Unknown if extension or metastasis; unstageable No TNM staging for Unknown Primary Site MD definition of unknown primary is different from registry definition From TNM Chapter 1: In cases where there is no evidence of a primary tumor or the site of the primary tumor is unknown, staging may be based on the clinical suspicion of the primary tumor with the T category classified as T0. 22 Treatment of Unknown Primary Traditionally, empiric chemotherapy Generalized chemo using drugs that work for many cancers 5% cure rate, but 35-40% response rate Example: Carbo-Taxol for women Based on most likely site of primary and histology as identified by tumor markers 23 Systemic Therapy Agents Metastatic adenocarcinoma Effective drugs (used in combination regimens) Carboplatin Cisplatin Docetaxel Etoposide Gemcitabine Paclitaxel Regimens mfolfox6 (oxaliplatin, 5-FU, Leucovorin) CapeOX (capecitabine, oxaliplatin) 24 8

9 Systemic Therapy Agents Metastatic squamous cell carcinoma Effective drugs (used in combination regimens) 5-FU Carboplatin Cisplatin Docetaxel Etoposide Gemcitabine Paclitaxel Regimens mfolfox6 (oxaliplatin, 5-FU, Leucovorin) 25 Emerging Technology De-emphasis on tissue of origin (primary site) and histologic subtype More emphasis on identifying genetic alterations through molecular profiling (multigene assays / biomarkers) Reportedly ~ 85% accurate Amenable to targeted therapies Treat the marker rather than the primary site 26 Markers and Targeted Therapies Unknown primaries tend to overexpress EGFR gefitinib, cetuximab, erlotinib, panitumumab BRAF vemurafinib C-kit/PDGFR imatinib (Gleevec), axitinib Ras panitumumab, cetuximab BCL2 Genasense, ABT-737, ABT-199 HER2 trastuzumab (Herceptin), pertuzumab (Perjeta), NeuVax P53 several molecules in clinical trials P13KCA several molecules in clinical trials 27 9

10 Is it really an unknown primary? (1) Male Elevated CEA Polyps on colonoscopy Biopsy positive for CK20 and CDX-2 Liver mets (adenocarcinoma) Family history of colorectal cancer 28 Is it really an unknown primary? (2) X-rays: 9/8/XX CT Chest: extensive mediastinal and rt hilar adenopathy which produces mild extrinsic compression of brachiocephalic vein and SVC. Findings most compatible w/metas ds. Mult irreg pulm nodules in RUL largest measuring 2.6 cm. Hepatic and splenic mets as well as bil adrenal mets. Labs: CA19-9: ; CEA: OP: bx of liver only Path: Hi gr CA favor PD Adenoca P site: Unknown: Possibly pancreaticobiliary, upper GI tract, lung, etc. Chemo: Palliative chemo only 29 Death Cert: Hypoxia due to pneumonia due to metastatic lung cancer Is it really an unknown primary? (3) Date of Dx: 05/31/XX X-ray: CT Abd-Pelv: Stones in gb.; MRI Abd: findings suspicious for severe acute pancreatitis. Extensive pancreatic edema as well as mod upper abd ascites.; Suspicious for ulcer involving pylorus or duodenal bulb. ; Cirrhosis. Path: Low gr papillary CA, fibrotic nodule adjacent to proximal gallbladder Histology: A pancreatic biliary source is reasonable--watch for further info; papillary low gr. CA pancreatic Death Certificate: Expired from a gastrointestinal malignancy, unknown type

11 Is it really an unknown primary? (4) Date of DX: 05/27/XX PE: Incidental finding-patient fell X-ray: 5/29/XX CNS mets, 5/29/XX spine/bone mets, 5/29/XX bil pulmonary lesions consistent with mets. OP: 5/28/XX Bx R posterior chest wall core bx Path: 5/28/XX Right posterior chest wall/torso, core bx poorly diff non-small cell carcinoma Histology: Adenoca 31 Is it really an unknown primary? (5) PE: No appetite, bloating, black stools, left side back pain OP: Bx Path: SU13-xxxx Primary Site: Unk?GI origin Histology: Adenoca, metastatic?gi origin Death Cert: Stomach cancer, 1 month 32 Is it really an unknown primary? (6) Date of DX: 07/24/XX Hx of Breast CA 10 yrs PTA and melanoma 8 yrs PTA PE: 92 y/o Cauc fem presents to ER w/increased ascites and swelling in bilat legs X-rays: 07/17/XX - CT Abd/Pelv Lg amt of ascites in abd and pelvis; bilat pleural effusions Path: 07/24/XX Ascites cytology-adenocaunknown primary Histology: Adenocarcinoma Death Cert: 8/11/XX--Pt. expired d/t abdominal carcinomatosis - ovarian

12 Abstracting an Unknown Primary Read the chart carefully, especially consults Ask the pathologist about any tests you don t understand Pay attention to how the patient is treated Follow back to the primary physician at time of abstracting Check back / follow up with MD again in 2-3 years If possible, access death certificate 34 Abstracting an Unknown Primary Use suggested site codes If primary site is identified, change site on abstract Central registries can follow-back to hospitals with a list of C80.9 and C76._ cases Document, document, document! Maybe it isn t really an unknown primary 35 Further Reading NCCN Guidelines for Occult Primary /occult.pdf Carcinoma of Unknown Primary Treatment Metastatic Cancer with Unknown Primary Site overview 36 12

13 Any Questions? 37 13