SEMINARIO DE PATOLOGÍA ENDOCRINA
Catarina Eloy
Mário Oliveira
Manuel Sobrinho Simões
Clinical history
24 year-old male with a 5cm nodule in the left lobe of
the thyroid.
• Euthyroid
• Previously healthy
• No familial history of thyroid disease
Year
2000
The patient was submitted to left lobectomy.
“Poorly differentiated thyroid carcinoma”
The patient was submitted to right lobectomy plus
isthmectomy and left cervical lymphadenectomy,
followed by radioactive iodine treatment.
Afterwards we received the case in consultation.
Few
months
latter
Macroscopic examination
LEFT LOBE (1
st
surgery)
Whitish nodule measuring 5.3cm in its largest dimension.
RIGHT LOBE, ISTHMUS and LEFT CERVICAL
LYMPH NODES (2 surgery)
No signs of neoplastic disease.
nd
Microscopic examination
H&E
40x
Microscopic examination
H&E
200x
Microscopic examination
H&E
400x
Microscopic examination
H&E
200x
Microscopic examination
H&E
400x
Microscopic examination - PASD
PASD
400x
Diagnosis?
Poorly differentiated carcinoma
Medullary carcinoma
Metastasis
Small cell neuroendocrine carcinoma
Primary extraeskeletal Ewing family tumour
Sent for consultancy to Porto (Also seen in
IPATIMUP by Prof. Juan Rosai)
Immunohistochemistry
Tg
40x
400x
Immunohistochemistry
Calcitonin
200x
TTF1
200x
CEA
400x
Immunohistochemistry
AE1AE3
34βE12
400x
400x
Immunohistochemistry
CK5
400x
CK19
200x
Gal 3
400x
CK7
400x
Immunohistochemistry
p63
40x
600x
Immunohistochemistry
NSE
N-CAM
Synapto
Chromo
400x
Diagnosis?
Poorly differentiated carcinoma
Medullary carcinoma
Metastasis & No primary tumour elsewhere
Small cell neuroendocrine carcinoma
Primary extraeskeletal Ewing family tumour
(PEEFT)
Year
2013
The patient is alive and well without additional
treatment 13 years after the diagnosis!
Immunohistochemistry
CD99
600x
20x
Molecular study
EWSR1
FLI1
The cytogenetic study using fluorescent in situ hybridization (break-apart probe)
disclosed the presence of the structural rearrangement EWSR1/FLI1
Tentative diagnosis - PEEFT
Present case versus PEEFT
Summary of the immunohistochemistry
Present case
Extra-osseous Ewing sarcoma
(Maldi et al)
Pan-cytokeratins
+
F
HMW-cytokeratins
F
-
CD99
+
+
Vimentin
-
+
p63
+
F
Chromogranin
-
-
Synaptophysin & NSE
-
+
50%
>60%
EWSR1/FLI1 rearrangement
EWSR1 rearrangement
Primary antibody
Ki67 labeling index
FISH analysis
Immunohistochemistry and EM
• Ultrastructure:
Epithelioid cells with
desmosomes and rare dense
granules without neuroendocrine
features
E-cadherin
400x
Epithelial differentiation
What to do with the EWSR1/FLI1 rearrangement in a
tumour with epithelial differentiation?
Atypical PNET/ES have been reported as having carcinomatous features.
EWSR1 rearrangement has been reported in several types of epithelial tumours.
Present
case
Favorable prognosis
Coexistence with papillary thyroid carcinoma-type follicles
Absence of cytoplasmatic glycogen and expression of vimentin and neuroendocrine markers
Epithelial differentiation
Diagnosis
Carcinoma of the thyroid with PEEFT features
(CEFTE)
Or
Atypical PEEFT of the thyroid with carcinomatous
features
Take home lesson
Funny small cell tumour of the thyroid carrying good prognosis.
Small cell non neuroendocrine carcinoma (Cruz et al)
EWSR1/FLI1 rearrangement was positive!
Present case versus Small cell non neuroendocrine carcinoma
Present case
Small cell non endocrine
carcinoma (Cruz et al)
Pan-cytokeratins
+
+
HMW-cytokeratins
F
F
CD99
+
+
Vimentin
-
-
p63
+
+
Chromogranin
-
-
Synaptophysin & NSE
-
-
50%
2%
EWSR1/FLI1 rearrangement
EWSR1/FLI1 rearrangement
Immunohistochemistry
Primary antibody
Ki67 labeling index
FISH analysis