Primary neuroendocrine carcinoma of the breast: radiologic and pathologic correlation

Primary neuroendocrine carcinoma of the breast: radiologic and pathologic correlation

    Primary Neuroendocrine Carcinoma of the Breast: Radiologic and Pathologic Correlation Yu Sung Yoon, Shin Young Kim, Ji-Hye Lee, Sung ...

1MB Sizes 0 Downloads 78 Views

    Primary Neuroendocrine Carcinoma of the Breast: Radiologic and Pathologic Correlation Yu Sung Yoon, Shin Young Kim, Ji-Hye Lee, Sung Yong Kim, Sun Wook Han PII: DOI: Reference:

S0899-7071(14)00144-2 doi: 10.1016/j.clinimag.2014.05.009 JCT 7631

To appear in:

Journal of Clinical Imaging

Received date: Revised date: Accepted date:

25 December 2013 9 May 2014 19 May 2014

Please cite this article as: Yoon Yu Sung, Kim Shin Young, Lee Ji-Hye, Kim Sung Yong, Han Sun Wook, Primary Neuroendocrine Carcinoma of the Breast: Radiologic and Pathologic Correlation, Journal of Clinical Imaging (2014), doi: 10.1016/j.clinimag.2014.05.009

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT

Primary Neuroendocrine Carcinoma of the Breast:

RI P

T

Radiologic and Pathologic Correlation

Yu Sung Yoon1, Shin Young Kim1, Ji-Hye Lee2, Sung Yong Kim3, Sun Wook Han3

Department of Pathology2, Department of Surgery3 Address correspondence to:

MA NU

Shin Young Kim, M.D.

SC

Soonchunhyang University Cheonan Hospital, Department of Radiology1,

Department of Radiology

Soonchunhyang University Cheonan Hospital, 23-20 Bongmyung-dong, Dongnam-gu, Cheonan, Chungchungnam-do, Korea, 330-721, E-mail) [email protected]

ED

Tel) +82-41-570-3515

AC

CE

PT

Fax) +82-41-579-9026

ACCEPTED MANUSCRIPT

Abstract

T

Primary neuroendocrine carcinoma of the breast (PNCB) is a rare type of breast cancer.

RI P

There have been few reports on PNCB and radiologic-pathologic correlation in PNCB has not been described thoroughly. We present a rare case of pathologically confirmed poorly

SC

differentiated PNCB removed via lumpectomy. Image findings on mammography, ultrasonography (USG), computed tomography (CT), magnetic resonance image (MRI) and

MA NU

positron emission tomography-computed tomography (PET-CT) are also presented.

AC

CE

PT

ED

Keywords: Neuroendocrine, Poorly differentiated, Breast, US, MRI

ACCEPTED MANUSCRIPT

Introduction

T

Neuroendocrine tumors can occur in a variety of extrapulmonary sites such as the breast,

RI P

larynx, gastrointestinal tract, prostate, bladder, ovary, and cervix. Neuroendocrine tumors affecting the breast are very rare and were first reported in 1983 [1-2]. Despite their rarity, it

SC

is important to differentiate them from other poorly differentiated breast cancers or metastatic small cell carcinoma of the lung because of the therapeutic or prognostic implications for

MA NU

these patients [2]. There are few studies sufficiently describing imaging and pathologic findings of primary neuroendocrine carcinoma of the breast (PNCB). Our case showed good

ED

correlation between radiologic and pathologic findings.

Case Report

PT

A 44-year-old woman visited our hospital for a palpable left breast mass first noticed three months ago. Physical examination revealed a 5cm sized fixed soft mass in the lower outer

CE

quadrant of the left breast. Mammography revealed a 1.8 cm sized indistinct round

AC

hyperdense mass in the lower outer quadrant of the left breast. There was no combined abnormal calcification (Fig. 1). On USG, a 1.7 cm sized partly angulated round hypoechoic mass with mild posterior acoustic enhancement was noted. Color doppler image showed slightly increased vascularity. There were no significantly enlarged lymph nodes in the ipsilateral axilla. The lesion was diagnosed as Breast Imaging-Reporting and Data System(BI-RADS) category 5, and a USG-guided core needle biopsy was performed (Fig.2). The histopathology result was invasive carcinoma with neuroendocrine features. MRI was performed using the 3.0T system as part of a surgical plan and to look for additional lesions. The mass had homogeneous low signal intensity on T1 weighted image (WI) and iso signal intensity on T2 WI. An early contrast enhanced T1 WI showed heterogeneous rapid initial

ACCEPTED MANUSCRIPT

enhancement. The dynamic enhancement curve showed a plateau (Fig.3). Contrast-enhanced

T

chest CT was performed to confirm the PNCB diagnosis. There were no mass-like lesions in

RI P

either lung fields, but a relatively well-defined heterogeneous enhancing mass was noted in the left breast parenchyma (Fig.4). PET-CT was performed as part of the metastatic work-up.

SC

Trans-axial fusion PET-CT image showed intense fluorodeoxyglucose (FDG) uptake (SUV = 7.94) in the left breast mass (Fig. 5). No additional lesion with increased FDG uptake was

MA NU

detected in the whole body or left axillary area. A lumpectomy was performed under general anesthesia.

Grossly, the tumor was pale grayish-white with a relatively smooth border and measured 2.2 x 2 cm (Fig.6). Microscopically, the tumor was densely cellular with tumor cells arranged in

ED

solid nests and trabeculae without tubule formation showing foci of rosette-like structures

PT

invading a collagenous stroma (Fig.7). The tumor cells were round to ovoid and exhibited mildly pleomorphic nuclei with a coarse chromatin pattern and moderate amount of granular

CE

eosinophilic cytoplasm (Fig.8). Mitosis was frequent. Immunohistochemically, tumor cells

AC

revealed diffuse cytoplasmic positivity for synaptophysin (Fig.9) and focal positivity for chromogranin. Progesterone and estrogen receptors were also positive. The final diagnosis was poorly differentiated neuroendocrine carcinoma. She had been treated 5 times with postoperative chemotherapy (cyclophosphamide + adriamycin). No evidence of local or distant metastasis or symptomatic discomfort was noted. Follow-up breast USG and mammography performed 2 months later revealed no evidence of recurrence.

ACCEPTED MANUSCRIPT

Discussion

T

Neuroendocrine tumors can occur in various sites of the body: the lung being the most

RI P

common site, while the breast is one of the rarest sites for an extrapulmonary primary neuroendocrine tumor [1-2]. PNCB is extremely rare, accounting for approximately less than

SC

0.1% of all variants of breast cancer and less than 1% of all neuroendocrine tumors of the body [9]. PNCB and neuroendocrine tumor of the lung have similar morphologic features.

MA NU

PNCB shows a broad spectrum of severity from relatively non-aggressive carcinoid tumor to highly aggressive small cell carcinoma [3, 4]. PNCB usually occurs in the 6th or 7th decade of life [5]. The new classification of PNCB by the World Health Organization Classification of Tumors of the Breast, 4th edition (2013), includes well-differentiated neuroendocrine tumor,

ED

poorly differentiated neuroendocrine carcinoma (small cell carcinoma), and carcinoma with

PT

neuroendocrine differentiation. A poorly differentiated neuroendocrine carcinoma is the rarest type [4].

CE

Imaging findings of PNCB have been described in only a few reported cases. Günhan-

AC

Bilgen et al. [6] reported that most examples of this tumor type showed hyperdense round masses with predominantly spiculated or lobulated margins on mammography. Mariscal et al. [3]reported PNCB as a partially obscured round hyperdense mass, similar to our case. They reported sonographic findings of PNCB as having mostly homogeneous echogenicity with some posterior acoustic enhancement. None of the cases showed posterior acoustic shadowing or had a cystic portion [6]. Another study[3] also reported combined posterior acoustic enhancement and a homogeneous hypoechoic solid mass. The PNBC in our case had homogeneous hypoechoic echo texture with posterior acoustic enhancement without cystic portion, which correlated with previously reported cases. MR images in our case were similar with those from other reports[1-6] with regard to the relatively homogeneous early

ACCEPTED MANUSCRIPT

enhancement pattern. There were some differing descriptions of the mass on mammography,

T

US, and MRI, wherein some reports noted microlobulated margins. CT showed a well-

RI P

defined heterogeneous enhancing mass without lung parenchymal lesion. Radiologic findings of PNCB were described as a relatively defined homogeneous solid mass with heterogeneous

SC

enhancement and no internal degenerative or necrotic portion. In Latif et al’s study[2], PETCT showed hypermetabolic activity in the breast mass and axillary lymph nodes. Our case

MA NU

also showed intense FDG uptake (SUV = 7.94) in the left breast mass without axillary lymph node involvement.

PNCB histogenesis is still unclear because the presence of neuroendocrine cells in the normal breast has not been conclusively shown[7]. Poorly differentiated PNCB contains

ED

sheets of small round cells that have dark nuclei, scant cytoplasm, fine granular nuclear

PT

chromatin, and indistinct nucleoli. Histologically, the differential diagnosis for PNCB should include Merkel cell neoplasm, malignant lymphoma, malignant melanoma, undifferentiated

CE

carcinoma, and metastatic small cell carcinoma of the lung. There is no distinct clinical

AC

feature that would reliably differentiate PNCB from other types of breast cancer [5]. It is difficult to distinguish a metastatic tumor from PNCB based on histology alone because of similarities in morphology and immunohistochemical patterns [8]. There were some histopathologic characteristics that have been previously reported. Immunohistochemical staining of the tumor cells for chromogranin, neuron-specific enolase, and synaptophysin are usually positive in PNCB. Microscopic evidence of neuroendocrine differentiation is found in more than 50% of the cell population. Presence of an in situ component of a common variant of breast cancer in histological sections have been found, as well as nuclear positivity for estrogen and progesterone receptors with absolute negativity for HER2/neu receptors [5, 9]. E-cadherin and Chromogranin A stains were positive in our case, while a Pan-CK stain done

ACCEPTED MANUSCRIPT

on the sentinel lymph node was negative.

T

Because of the extreme rarity and consequent paucity of long-term statistical data, it is

RI P

nearly impossible to draw a conclusive prognosis. Low-grade poorly differentiated PNCB responds well to conventional treatment [5]. However, large-sized tumor, small cellularity,

SC

high nuclear grade, no estrogen and progesterone receptors, lymphovascular invasion, lymph node involvement, and distant metastases are adverse prognostic factors associated with poor

MA NU

outcome [9].PNCB is rare andshows a broad spectrum of severity. As a result, no standard treatment for this disease exists. The most effective treatment includes surgical removal such as modified radical mastectomy with axillary lymph node dissection and additional adjuvant chemotherapy. There was a discrepancy between surgical treatment of our patient and

ED

recommended surgical treatment because of the patient’s demand for minimal surgery.

PT

Considering that the biological characteristics of PNCB are similar to small cell carcinoma of the lung, effective drugs for the latter, such as platinum compounds and etoposide, were

CE

selected to treat these patients [10].

AC

Poorly-differentiated PNCB is the rarest type of PNCB; consequently, few studies have introduced imaging and pathologic findings. We present a rare case of breast cancer and its diagnostic imaging findings with clinical and pathologic correlation. This may help to differentiate PNCB from other breast cancers and properly treat future cases.

ACCEPTED MANUSCRIPT

References

T

1. Kitakata H, Yasumoto K, Sudo Y, et al. A case of primary small cell carcinoma of the

RI P

breast. Breast Cancer 2007;14:414-419

2. Latif N, Rosa M, Samian L, et al. An Unusual Case of Primary Small Cell

SC

Neuroendocrine Carcinoma of the Breast. Breast J. 2010:16:647-651 3. Mariscal A, Balliu E, Díaz R, et al. Primary Oat Cell Carcinoma of the Breast :

MA NU

Imaging Features. 2004;183:1169-1171

4. Sinn HP, Kreipe H. A Brief Overview of the WHO Classification of Breast Tumors, 4th Edition, Focusing on Issues and Updates from the 3rd Edition. Breast Care 2013;8:149-154

ED

5. Irshad A, Ackerman SJ, Pope TL, et al. Rare Breast Lesions: Correlation of Imag- ing

PT

and Histologic Features with WHO Classification. Radiographics 2008;28:1399-1414 6. Günhan-Bilgen I, Zekioglu O, Ustün EE, et al. Neuroendocrine differentiated breast

CE

carcinoma: imaging features correlated with clinical and histopathological findings.

AC

EurRadiol 2003;13:788-793 7. Adegbola T, Connolly CE, Mortimer G. Small cell neuroendocrine carcinoma of the breast: a report of three cases and review of the literature. J ClinPathol. 2005;58:775778 8. Nicoletti S, Papi M, Drudi F, et al. Small cell neuroendocrine tumor of the breast in a 40 year-old woman: a case report. J Med Case Rep. 2010; 30;4:201 9. Rehman A. Primary Neuroendocrine Carcinoma of the Breast. J Coll Physicians Surg Pak. 2013;23:282-284. 10. Ge QD, Lv N, Cao Y, et al. A case report of primary small cell carcinoma of the breast and review of the literature.Chin J Cancer. 2012;31(7):354-358

ACCEPTED MANUSCRIPT

T

Figure Legends

RI P

Fig. 1. (a) Mediolateral oblique mammogram view and (b) craniocaudal mammogram view shows a 1.8cm sized partially obscured round hyperdense mass in the lower outer quadrant of

SC

the left breast (black arrow).

Fig.2. (a), (b). Ultrasonography reveals a 1.7 cm sized partly angulated round hypoechoic

is noted in the color doppler image.

MA NU

mass with mild posterior acoustic enhancement (white arrow). Slightly increased vascularity

Fig.3. MRI was performed using the 3.0T system. (a) On axial non-fat-saturated T1 weighted images, mass shows round, smooth, homogeneous, low signal intensity (white arrow). (b) On

ED

axial fat-saturated T2 weighted images, mass shows iso signal intensity. (c) Axial fat-

PT

saturated pre-contrast-enhanced, (d) early (2 min) contrast enhanced, and (e) delayed (6 min) contrast enhanced axial T1 weighted images after bolus administration of gadolinium based

CE

contrast agent show heterogeneous enhancement. (f) Axial subtraction image reveals

AC

heterogeneous rapid initial enhancement. (g) Kinetic curve derived from signal intensity measurements in target lesion show a plateau. On all MRI images, there is a 0.6cm sized circumscribed oval homogeneously enhancing nodule in anteromedial aspect from the dominant mass which shows early enhancement without washout pattern. Because the enhancement pattern of it was similar with main mass, excised together. This lesion confirmed as fibroadenomatous change. Fig.4. (a), (b), (c). CT shows a well-defined round heterogeneous enhancing mass (white arrow) in left breast parenchyma. Fig.5. Trans-axial fusion image of PET-CT shows FDG uptake (SUV = 7.94) in left breast mass (white arrow).

ACCEPTED MANUSCRIPT

Fig.6. Tumor measures 2.2 cm and pale grayish-white with a relatively smooth border (black

T

arrow).

RI P

Fig. 7. Tumor is densely cellular with cells arranged in solid nests(black arrowhead) and trabeculaeshowing foci of rosette-like structures(white arrowhead).Tumor cells(black arrow)

SC

invading collagenous stroma (white arrow)(H&E, x 200).

Fig. 8. Tumor cells are round to ovoid with moderately pleomorphic nuclei (black arrow) and

MA NU

coarse chromatin pattern. A moderate amount of granular eosinophilic cytoplasm is present. Mitosis was frequent (white arrow) (H&E, x400).

AC

CE

PT

ED

Fig. 9. Tumor cells show diffuse cytoplasmic positivity for synaptophysin (x 400).

ACCEPTED MANUSCRIPT

AC

CE

PT

ED

MA NU

SC

RI P

T

Figure 1a

ACCEPTED MANUSCRIPT

AC

CE

PT

ED

MA NU

SC

RI P

T

Figure 1b

ACCEPTED MANUSCRIPT

AC

CE

PT

ED

MA NU

SC

RI P

T

Figure 2a

ACCEPTED MANUSCRIPT

AC

CE

PT

ED

MA NU

SC

RI P

T

Figure 2b

ACCEPTED MANUSCRIPT

AC

CE

PT

ED

MA NU

SC

RI P

T

Figure 3a

ACCEPTED MANUSCRIPT

AC

CE

PT

ED

MA NU

SC

RI P

T

Figure 3b

ACCEPTED MANUSCRIPT

AC

CE

PT

ED

MA NU

SC

RI P

T

Figure 3c

ACCEPTED MANUSCRIPT

AC

CE

PT

ED

MA NU

SC

RI P

T

Figure 3d

ACCEPTED MANUSCRIPT

AC

CE

PT

ED

MA NU

SC

RI P

T

Figure 3e

ACCEPTED MANUSCRIPT

AC

CE

PT

ED

MA NU

SC

RI P

T

Figure 3f

ACCEPTED MANUSCRIPT

AC

CE

PT

ED

MA NU

SC

RI P

T

Figure 3g

ACCEPTED MANUSCRIPT

AC

CE

PT

ED

MA NU

SC

RI P

T

Figure 4a

ACCEPTED MANUSCRIPT

AC

CE

PT

ED

MA NU

SC

RI P

T

Figure 4b

ACCEPTED MANUSCRIPT

AC

CE

PT

ED

MA NU

SC

RI P

T

Figure 4c

ACCEPTED MANUSCRIPT

AC

CE

PT

ED

MA NU

SC

RI P

T

Figure 5

ACCEPTED MANUSCRIPT

AC

CE

PT

ED

MA NU

SC

RI P

T

Figure 6

ACCEPTED MANUSCRIPT

AC

CE

PT

ED

MA NU

SC

RI P

T

Figure 7

ACCEPTED MANUSCRIPT

AC

CE

PT

ED

MA NU

SC

RI P

T

Figure 8

ACCEPTED MANUSCRIPT

AC

CE

PT

ED

MA NU

SC

RI P

T

Figure 9