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Transcript of Invasive mammary carcinoma with neuroendocrine ...ijhbr.com/pdf/4 2014 42-46.pdf · Neuroendocrine...
International J. of Healthcare and Biomedical Research, Volume: 2, Issue: 3 , April 2014 , Pages 42-46
42 www.ijhbr.com ISSN: 2319-7072
Case Report:
Invasive mammary carcinoma with neuroendocrine differentiation: a
diagnostic challenge
Dr. Gajender Singh, Dr. Pansi Gupta, Dr. S.K.Mathur, Dr. Sant Prakash Kataria, Dr. Sanjay Kumar
Name & Address of Institution: Department of Pathology, Pt B.D. Sharma PGIMS, Rohtak, Haryana, India
Corresponding author : Dr Pansi Gupta
Abstract :
Neuroendocrine differentiation has been reported in both in situ and infiltrating breast cancers. The prognostic
significance of neuroendocrine differentiation in mammary carcinoma is unclear. The spectrum ranges from
undifferentiated small cell carcinoma to ductal carcinoma in situ with neuroendocrine differentiation. Mucinous
carcinomas of the breast appear to have the greatest association with neuroendocrine differentiation. We add to the
literature a case of a morphologically composite mammary infiltrating ductal carcinoma with diffuse neuroendocrine
differentiation as demonstrated by immunohistochemical staining. We reported a case of 76 year old female
diagnosed as infiltrating ductal carcinoma in which there was a morphologically conventional-appearing infiltrating
ductal component admixed with nests of cells that resembled a carcinoid tumor and initially mimicked the
appearance of intraductal carcinoma. Immunohistochemical stains for synaptophysin and chromogranin
demonstrated diffuse, strong positivity uniformly throughout the tumor, even in the more conventional-appearing
areas. We concluded that this was an infiltrating ductal carcinoma with morphologic and immunohistochemical
evidence of neuroendocrine differentiation. The presence of neuroendocrine differentiation in a morphologically
composite tumor should be reported but that the tumor should essentially be classified according to existing schemes
of ductal and lobular carcinomas and variants. There is no evidence that neuroendocrine differentiation is
prognostically significant.
Keywords: Breast neoplasm; Neuroendocrine tumor
Introduction
Neuroendocrine differentiation of breast is a rare
tumor. They arise from cells able to produce peptide
and amines referred to as diffuse neuroendocrine
system. The significance of neuroendocrine
differentiation in carcinomas of the breast remains
unclear. The spectrum ranges from undifferentiated
small cell carcinoma to ductal carcinoma in situ with
neuroendocrine differentiation. Mucinous carcinomas
of the breast appear to have the greatest association
with neuroendocrine differentiation.1 It is likely that
neuroendocrine mammary carcinomas derive from
progressive neuroendocrine differentiation in a subset
of cancerous cells rather than from pre-existent
endocrine cells . Neuroendocrine differentiation can
be found in different histotypes of breast carcinoma,
including in situ and invasive ductal, lobular, colloid,
papillary breast cancer.2 Clayton et al. detected the
presence of argyrophilic and dense granules by
electron microscopy in different histotypes of
mammary breast cancer.3
International J. of Healthcare and Biomedical Research, Volume: 2, Issue: 3 , April 2014 , Pages 42-46
43 www.ijhbr.com ISSN: 2319-7072
Case report
A 76-year-old woman with no significant medical
history was found to have a palpable left breast mass
in the upper outer quadrant. A fine-needle aspiration
cytology was performed. Smears showed highly
necrotic ductal carcinoma. No cytologic features of
neuroendocrine differentiation were noted either
initially or upon review. Then patient underwent
modified radical mastectomy, specimed measured
15x15x6cm. On serial sectioning a growth measuring
2x1.5 cm was identified. Cut surface was greyish
white. Tumor was 0.2cm away from resected base
grossly. Representative microsections examined
showed infiltrating ductal carcinoma breast with
neuroendocrine differentiation. Focal areas of mucin
production was also seen. Overlying skin, nipple and
areola were free from tumor infiltration. Resected
base showed infiltration by tumor. Lymph nodes
isolated (8) showed reactive hyperplasia.
Special stains for the neuroendocrine markers
synaptophysin, chromogranin and neuro specific
enolase were performed and showed diffuse
positivity in both the nests and in the more
conventional invasive ductal carcinoma.
Morphologically transitional areas were also strongly
and diffusely positive for synaptophysin and
chromogranin. Positive and negative controls were
appropriate. Adjacent non-neoplastic breast was
negative. tion. Additional tests performed included
estrogen, progesterone, and HER-2/neu receptor
staining. The tumor was positive for estrogen
receptors and progesterone and HER-2/neu receptors.
Modified radical mastectomy was performed.
Discussion
Neoplasms with neuroendocrine differentiation do
not constitute a specific histopathological category of
female mammary carcinoma, but it is apparent that
there is a group of mammary carcinomas capable of
producing ectopic hormonal substances. The
recognition of these features is necessary for defining
their clinical characteristics. 4 Multiple studies have
been undertaken to identify a pre-existing population
of neuroendocrine cells in breast tissue. An early
study demonstrated the presence of chromogranin-
reactive endocrine cells in normal breast tissue as
well as in so-called argyrophilic or carcinoid tumors
of the breast. Other studies demonstrated dense-core
granules by electron microscopy.1 Pure carcinoid
tumors of the breast have been reported, as have
small cell carcinomas and composite tumors (ie,
tumors with more conventional-appearing types of
breast carcinomas admixed with or coexpressing
neuroendocrine carcinoma morphologically or
immunohistochemically).
Among composite tumors, the mucinous carcinoma is
the type most commonly associated with
neuroendocrine differentiation.1Neuroendocrine (NE)
was not recognized as a single entity until the last
WHO’s classification. This classification
differentiates between four different subtypes: (i)
small-cell carcinoma (SCC); (ii) large-cell
carcinoma; (iii) solid NE carcinoma; and (iv) atypical
carcinoid tumor. For simplification, this section
describes the solid neuroendocrine subtype (SN)
which represents a better prognosis group. (The SCC
subtype is described in the ‘poor prognosis, ER
positive’ section.) 5
Histologically the neuroendocrine component
resembles lung and gastrointestinal neuroendocrine
tumors. It is characterized by cellular monotony,
nuclear palisading, pseudorosette formation, loss of
cell cohesion, and abundant eosinophilic cytoplasm
and nuclei with stippled (‘salt and pepper’)
chromatin . Nevertheless these features per se are not
International J. of Healthcare and Biomedical Research, Volume: 2, Issue: 3 , April 2014 , Pages 42-46
44 www.ijhbr.com ISSN: 2319-7072
sensitive enough to rule in a diagnosis because they
are inconsistently present. A panel of the most
sensitive and specific IHC neuroendocrine markers
(chromogranin A or B and synaptophysin) are
known.6
Main reported morphological features in
neuroendocrine breast cancer are:
- production of mucin, retained into the cells
or secreted in extracellular milieu;
- presence of insular structures separated by
fibrovascular stroma;
- low nuclear grade and granulous cytosol.
There are no specific clinical features associated with
mammary carcinomas that exhibit structural or
histochemical evidence of endocrine differentiation,
so most of the lesions are palpable tumors or can be
detected by imaging.2
Histological grade is one of the most important
parameter in disease clinical development. High
grade neuroendocrine carcinomas show high
proliferation rate and poor prognosis. Low grade
neuroendocrine carcinomas with low proliferation
rate are be consider to have a better prognosis.
Another prognostic parameter is co-expression of
neuroendocrine and non-neuroendocrine proteins
such as glycoproteins and apocrine proteins. This
capability is present in well differentiated mammary
breast carcinomas while poor differentiated
carcinomas don’t show it .2
Sapino et al. has shown that mucin producing
carcinomas and pure apocrine carcinomas have a
better prognosis with a 5 years overall survival longer
than poor differentiated neuroendocrine carcinomas.8
Finally ER expression is an important prognostic
parameter in neuroendocrine breast carcinoma and
correlates to a long survival.2
Differential diagnosis should include direct invasion
of the breast by Merkel cell carcinoma, malignant
lymphoma (either primary or as a manifestation of
systemic disease), carcinoid tumor, and malignant
melanoma, which should be excluded by the exact
location and extension of the tumor and by
immunohistochemical stains, such as leukocyte
common antigen, neuroendocrine markers, S100
protein, and HMB-45, respectively. Modified radical
mastectomy with axillary lymph node dissection
seems to be the treatment of choice, with adjuvant
radiation, chemotherapy, or both, based on the
clinical stage and presence of metastasis.7
Conclusion
The presence of neuroendocrine differentiation in a
morphologically composite tumor should be reported
but that the tumor should essentially be classified
according to existing schemes of ductal and lobular
carcinomas and variants.
FIG 1: H&E VIEW OF BREAST TUMOR (10x)
International J. of Healthcare and Biomedical Research, Volume: 2, Issue: 3 , April 2014 , Pages 42-46
45 www.ijhbr.com ISSN: 2319-7072
FIG 2: H&E VIEW OF BREAST TUMOR (20x)
FIG 3: H&E VIEW OF NEUROENDOCRINE
DIFFERENTIATION (20x)
FIG 4:ER (20x)
FIG 5: PR (20x)
FIG 6: SYNAPTOPHYSIN (20x)
FIG 7: CHROMOGRANIN (20x)
FIG 8: NSE(20x)
International J. of Healthcare and Biomedical Research, Volume: 2, Issue: 3 , April 2014 , Pages 42-46
42 www.ijhbr.com ISSN: 2319-7072
References
1. David O, Bhattacharjee M. Diffuse Neuroendocrine Differentiation in a Morphologically Composite
Mammary Infiltrating Ductal Carcinoma. Arch Pathol Lab Med.2003;127:133-4.
2. Noccioli P, Grossi S, Tavoletta S, Scognamiglio MT, Natoli C, Cianchetti E et al. Neuroendocrine tumors
of the breast: our experience." Clinica Oncologica PO “G. Bernabeo,” Dipartimento di Neuroscienze,
Chieti, Italy.
3. Clayton F, Ordonez NG, Sibley RK, Hanssen G: Argyrophilic breast carcinomas. Evidence of
lactational differentiation. Am J Surg Pathol. 1982; 6: 323-33.
4. Filho OG, Miiji LNO, Vainchenker M, Gordan AN. Breast cancer with choriocarcinomatous and
neuroendocrine features. Sao Paulo Medical J. 2001;6: 154-5.
5. Yerushalmi, R, Hayes MM, Gelmon KA. Breast carcinoma—rare types: review of the literature. Annals of
oncology 2009;20:1763-70.
6. Angarita FA, Rodríguez JL, Meek E, Sánchez JO, Tawil M, Torregrosa L. Locally-advanced primary
neuroendocrine carcinoma of the breast: case report and review of the literature. World journal of surgical
oncology 2013;11(1):1-11.
7. Tanwani AK, Khalid A, Mudassara. Neuroendocrine Carcinoma of Breast. Ann. Pak. Inst. Med. Sci.
2008;4(3), 171-3.
8. Sapino A, Righi L, Cassoni P, Pietribiasi F, Bussolati G. Expression of the neuroendocrine phenotype in
carcinomas of the breast. Semin Diagn Pathol 2000;17:127-37.
46
Date of submission: 29 January 2014, Date of provisional acceptance: 12 Feb 2013
Date of Final acceptance: 22 March 2014 Date of Publication: 07 April 2014
Source of support: Nil; Conflict of interest: Nil