Unknown primary tumors :common misdiagnosis

Oscar NappiUOSC di Anatomia patologica

AORN A. Cardarelli - Napoli

Shapira DV, Jarrett ARThe need to consider survival, otcome and expense when

evalueting and treating patients with unknown primary carcinomaArch 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

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 )

M 64 ysCerebral mass

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 ?

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

Diagnosi finale

S100 HMB45

Metastatic melanoma

http://www.pathconsultddx.com/pathCon/largeImage?pii=S1559-8675(06)70421-1&figureId=fig1

Polygonal large cell tumor Immunoistochemical algorytm

Unknown primary tumorsCommon misdiagnosis

Unknown primary tumorsDangerous misdiagnosis

• Not diagnosing a malignant lymphoma• Not diagnosing an endocrine tumor • Not diagnosing other neoplasias with a favorable ( or relatively favorable ) therapeutical approach

Some neoplasias with a favorable

( or relatively favorable ) therapeutical approach

• Breast• Prostate• Extragonadal germ cell • “Peritoneal carcinoma”• Others

CD45

Large cell B lymphoma

Cytokeratin expression in hematological neoplasms:a tissue microarray study on 866 lymphoma and

leukemia cases

Adams H, Schmid P, et alPathol Res Pract 204 : 569- 573, 2008

0,4% HD0,6% B-LCLO,7 % Peripheral T cell Lymphoma0,7% Myeloma4% Small cell ymphoma26% Mantle cell lymphoma

Case 1

Pazient : F ys 46Clinics and imagingfavour a diagnosis ofmeningioma

CK 20 LCA

CK

Mammaglobin

CK7

HER2

ER

IHC in distinguish SCC and AC in poorly differentiated lung tumours

TypeTTF-1

p6334betaH11

Napsin A

SCC _ _ _ +++ _ _ _

ADENO +++ _ _ _ +++

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

TTF1

Napsin A

Clinical case

• Metastatic lung adenocarcinoma

Also positive in mesothelioma and in so called Primary peritoneal carcinoma

Clinical case

• M 38 ys• Axillary lymphadenopathy, retroperitoneal mass• No other apparent neoplastic lesions found• A lymphadenectomy is performed

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

Clinical case

• CD 30 +++• PLAP ++-• OCT 4 +++

Germ cell tumor Embryonal carcinoma

CD30

Clinical Case

• Male ys 63

• Multiple hepatic nodules

• At a first preliminary screening by CAT no other neoplastic lesions

found

?

Case

Preliminary immunohistochemical study :• CD45 NEGATIVO• HMB45 NEGATIVO• S-100 NEGATIVO• VIMENTINA NEGATIVA• Pan CK POSITIVA

TTF-1

CK7

Poorly differentiated adenocarcinoma of the lung ?

NE Markers !!

• Chromogranin A• Synaptophisin• CD56• CD57

• Negative• Weakly and Focal +

Ki67 > 15%

High grade NE large cell carcinoma of the lung CD56

Dangerous misdiagnosis

Metastatic mimicking primary tumors• Lung• Liver• Ovary• Thyroid• Breast• Any organ

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

Grazie