Catarina Eloy

Mário Oliveira

Manuel Sobrinho Simões

SEMINARIO DE PATOLOGÍA ENDOCRINA

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

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.

Year

2000

Few

months

latter

Macroscopic examination

LEFT LOBE (1st surgery)

Whitish nodule measuring 5.3cm in its largest dimension.

RIGHT LOBE, ISTHMUS and LEFT CERVICAL

LYMPH NODES (2nd surgery)

No signs of neoplastic disease.

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

34βE12

400x

AE1AE3

400x

Immunohistochemistry

CK5

400x

CK19

200x

CK7

400x

Gal 3

400x

Immunohistochemistry

p63

40x

600x

Immunohistochemistry

Chromo

400x

Synapto

N-CAM

NSE

Diagnosis?

Poorly differentiated carcinoma

Medullary carcinoma

Metastasis & No primary tumour elsewhere

Small cell neuroendocrine carcinoma

Primary extraeskeletal Ewing family tumour

(PEEFT)

The patient is alive and well without additional

treatment 13 years after the diagnosis!

Year

2013

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) Primary antibody

Pan-cytokeratins + F

HMW-cytokeratins F -

CD99 + +

Vimentin - +

p63 + F

Chromogranin - -

Synaptophysin & NSE - +

Ki67 labeling index 50% >60%

FISH analysis EWSR1/FLI1 rearrangement EWSR1 rearrangement

Immunohistochemistry and EM

E-cadherin

400x

• Ultrastructure:

Epithelioid cells with

desmosomes and rare dense

granules without neuroendocrine

features

Epithelial differentiation

What to do with the EWSR1/FLI1 rearrangement in a

tumour with epithelial differentiation?

Favorable prognosis

Coexistence with papillary thyroid carcinoma-type follicles

Absence of cytoplasmatic glycogen and expression of vimentin and neuroendocrine markers

Epithelial differentiation

Present

case

Atypical PNET/ES have been reported as having carcinomatous features.

EWSR1 rearrangement has been reported in several types of epithelial tumours.

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)

B D

EWSR1/FLI1 rearrangement was positive!

Present case versus Small cell non neuroendocrine carcinoma

Immunohistochemistry Present case

Small cell non endocrine

carcinoma (Cruz et al) Primary antibody

Pan-cytokeratins + +

HMW-cytokeratins F F

CD99 + +

Vimentin - -

p63 + +

Chromogranin - -

Synaptophysin & NSE - -

Ki67 labeling index 50% 2%

FISH analysis EWSR1/FLI1 rearrangement EWSR1/FLI1 rearrangement