Transcript Diapositiva 1

PRIMARY NON-SMALL CELL NEUROENDOCRINE CARCINOMA OF THE BREAST:
ANALYSIS OF A SERIES
YIELDING RESULTS CONFLICTING WITH
DATA IN THE LITERATURE
M. Bisceglia, L. Dicandia, M. Vairo, L. Zaffarano,
F. Scaramuzzi, D. Urbano.
Department of Pathology, IRCCS “Casa Sollievo
della Sofferenza” Hospital, San Giovanni
Rotondo.
Background.
• TTF-1 is a nuclear transcription factor expressed at the
onset of thyroid, lung, and ventral diencephalic
development (1).
• Accordingly, TTF-1 is frequently expressed in both benign
and malignant epithelial-derived tumors of the lung and
thyroid, including small cell carcinomas (SCC), welldifferentiated neuroendocrine tumors (WDNET) from these
two organs, and large cell neuroendocrine carcinoma
(LCNEC) of the lung.
• Over the last years a considerable proportion of
extrapulmonary and extrathyroid neuroendocrine
tumors (NET), mostly SCC type, of disparate origins
have been proved reactive for TTF-1.
• Hence, TTF-1 expression cannot be used to
distinguish pulmonary from extrapulmonary SCC or
LCNEC, the only exception being cutaneous Merkel
cell tumor which is consistently negative for TTF-1.
• Even WDNET of digestive tract and pancreas (with the
exception of 2 cases in large series from the digestive
tract), NET of the adrenal and extra-adrenal
paraganglia, and endocrine tumors of pituitary and
parathyroid are also consistently TTF-1 negative (for a
review see Bisceglia et al 2).
Design.
• NETs of breast, partly due to their rarity, have not been
extensively examined in this respect.
• To the best of our knowledge, 4 of only 6 primary SCCs of
breast investigated for TTF-1 expression 3-7 have been
positive 4,6,7, drawn from fewer than 40 cases mentioned
in the literature (35 of these fully reported 4,6,7).
• On the other hand, we have found only one
study assessing TTF-1 expression in non-small cell
neuroendocrine carcinomas of breast, according to which
5 of 5 proved positive for TTF17.
We selected from our archival materials 14 primary
invasive NETs of the breast (5 so-called carcinoid
tumors of Cubilla-Woodruff type, 2 neuroendocrine
carcinomas-NOS, 2 IDCs with neuroendocrine
features, 1 lobular carcinoma with neuroendocrine
features, and 4 colloid carcinomas type B).
All documented cases were positive
for at least 2 neuroendocrine markers
(chromogranin A and synaptophysin in all),
but 2 which were positive for one of these
markers together with positive argyrophilia.
Chromogranin A
Synaptophysin
Synaptophysin
Argyrophilic stain
Chromogranin A
• These cases were immunostained according to the
following protocol: heat-induced antigenic retrieval on
deparaffinized 4 µm sections for 2 cycles, each of 15
minutes, in 10 mM citrate buffer (pH 6.0) using a 360 W
microwave oven.
• The antibody to TTF-1 used was from clone 8G7G3/1
(1:30 dilution; DakoCytomation, Carpinteria, CA, USA).
• Immunohistochemical staining was performed using
the labeled streptavidin-biotin peroxidase complex
system (LSAB2) according to the manufacturer’s
recommendations in a DAKO Autostainer.
Results
All cases were unreactive to TTF-1.
TTF-1
Conclusion.
• Based on our own experience, TTF-1 may help
in distinguishing NETs of the breast, other than
SCC, from WDNETs of lung (classic and
atypical carcinoids).
• The lack of TTF-1 expression in our cases is in
contrast with previously reported data in the
literature, therefore additional studies are
strongly encouraged and would be commended.
References
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