1. Unknown primary tumors : common misdiagnosis Oscar Nappi UOSC di Anatomia patologica AORN A. Cardarelli - Napoli

5. Shapira DV, Jarrett AR The need to consider survival, otcome and expense when evalueting and treating patients with unknown primary carcinoma Arch Intern Med 155 : 2050-2054, 1995 56 pts with CUP The average cost to each patient for clinical procedures was 17.973 dollars Only in 4 cases the primary tumor was found None of the neoplasms was deemed curable and less than 20% of the patients survived more than 12 months after initiation of therapy

6. Pathologist’s role in management of unknown primary tumors Conventional cyto- histologic studies correlated to clinical setting IMMUNOHISTOCHEMICAL STUDIES Molecular biomarkers microRNAs GEP ( gene expression profiling )

7. M 64 ys Cerebral mass

9. Questo è un linfoma maligno anaplastico Guarda il citoplasma…per me è un sarcoma epiteliode ! Ma..! Le cellule sono incise e macronucleolate. E se fosse un carcinoma ?

10. Neoplasia maligna, n.a.s., quadro compatibile con carcinoma scarsamente differenziato (origine ignota) metastatico Diagnosi finale

11. S100 HMB45 Metastatic melanoma

13. Polygonal large cell tumor Immunoistochemical algorytm

14. Unknown primary tumors Common misdiagnosis

15. Unknown primary tumors Dangerous misdiagnosis Not diagnosing a malignant lymphoma Not diagnosing an endocrine tumor Not diagnosing other neoplasias with a favorable ( or relatively favorable ) therapeutical approach

16. Some neoplasias with a favorable ( or relatively favorable ) therapeutical approach Breast Prostate Extragonadal germ cell “Peritoneal carcinoma” Others

18. CD45 Large cell B lymphoma

19. Cytokeratin expression in hematological neoplasms: a tissue microarray study on 866 lymphoma and leukemia cases Adams H, Schmid P, et al Pathol Res Pract 204 : 569- 573, 2008 0,4% HD 0,6% B-LCL O,7 % Peripheral T cell Lymphoma 0,7% Myeloma 4% Small cell ymphoma 26% Mantle cell lymphoma

24. Case 1 Pazient : F ys 46 Clinics and imaging favour a diagnosis of meningioma

26. CK 20 LCA CK Mammaglobin CK7

27. HER2 ER

34. IHC in distinguish SCC and AC in poorly differentiated lung tumours Type TTF-1 p63 34betaH11 Napsin A SCC_ _ _ +++ _ _ _ ADENO +++ _ _ _ +++

35. Clinical Case M 47 ys Multiple bone metastasis ( 2 vertebral bodies, femur ) and multiple nodules in both lungs FNA CAT-guided of a peripheral lung nodule

36. TTF1 Napsin A

37. Clinical case Metastatic lung adenocarcinoma

38. Also positive in mesothelioma and in so called Primary peritoneal carcinoma

39. Clinical case M 38 ys Axillary lymphadenopathy, retroperitoneal mass No other apparent neoplastic lesions found A lymphadenectomy is performed

41. Clinical case Immunohistochemical study pan CK positive CK 7 positive CK 20 negative PSA negative TTF-1 negative napsin A negative villin negative Adenocarcinoma NOS

42. Clinical case CD 30 +++ PLAP ++- OCT 4 +++ Germ cell tumor Embryonal carcinoma CD30

44. Clinical Case Male ys 63 Multiple hepatic nodules At a first preliminary screening by CAT no other neoplastic lesions found ?

46. Case Preliminary immunohistochemical study : CD45 NEGATIVO HMB45 NEGATIVO S-100 NEGATIVO VIMENTINA NEGATIVA Pan CK POSITIVA

47. TTF-1 CK7 Poorly differentiated adenocarcinoma of the lung ?

48. NE Markers !! Chromogranin A Synaptophisin CD56 CD57 Negative Weakly and Focal + Ki67 > 15% High grade NE large cell carcinoma of the lung CD56

49. Dangerous misdiagnosis Metastatic mimicking primary tumors Lung Liver Ovary Thyroid Breast Any organ

50. METASTASI ENDOBRONCHIALI: QUADRI RADIOLOGICI INDISTINGUIBILI DALLA NEOPLASIA POLMONARE PRIMITIVA METASTASI A LOCALIZZAZIONE ENDOBRONCHIALE DA TUMORI EXTRA-POLMONARI: STUDIO EPIDEMIOLOGICO E CLINICO-PATOLOGICO Ca sigma Ca stomaco

52. Grazie