- Email: [email protected]
Metastatic gastrinoma in the breast mimicking primary solid papillary carcinoma
Metastatic Gastrinoma in the Breast Mimicking Primary Solid Papillary Carcinoma Michael Burt BA, Rashna Madan MBBS, Fang Fan MD, PhD PII: DOI: Reference:
S0046-8177(16)30123-X doi: 10.1016/j.humpath.2016.05.024 YHUPA 3931
To appear in:
Human Pathology
Received date: Revised date: Accepted date:
12 February 2016 26 April 2016 23 May 2016
Please cite this article as: Burt Michael, Madan Rashna, Fan Fang, Metastatic Gastrinoma in the Breast Mimicking Primary Solid Papillary Carcinoma, Human Pathology (2016), doi: 10.1016/j.humpath.2016.05.024
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 Metastatic Gastrinoma in the Breast Mimicking Primary Solid Papillary
T
Carcinoma.
RI P
Michael Burt BA, Rashna Madan MBBS, Fang Fan MD, PhD*
SC
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS
NU
66160
MA
* Corresponding author:
Fang Fan, MD, PhD, Department of Pathology and Laboratory Medicine, University of Kansas Medical
PT
Office phone 913-588-1184.
ED
Center, 1606 KU Hospital, 3901 Rainbow Blvd., Kansas City, KS 66160. Email: [email protected];
CE
Conflict of interest: None
AC
Funding disclosures: None
Keywords: Breast solid papillary carcinoma; Metastatic gastrinoma; neuroendocrine tumor Running title: Metastatic gastrinoma in the breast
ACCEPTED MANUSCRIPT Summary: We report a case of metastatic gastrinoma to the breast morphologically mimicking solid papillary carcinoma of the breast. A 59-year-old woman presented with a hypoechoic right breast mass that histologically revealed solid nests of small monotonous tumor cells, fibrovascular cores, and round to oval nuclei with fine
T
chromatin and small prominent nucleoli. Immunohistochemistry demonstrated chromogranin and synaptophysin
RI P
positivity. Tumor prognostic markers showed weak positivity for estrogen receptor and negativity for progesterone receptor. Although an initial diagnosis of solid papillary carcinoma was rendered, subsequent
SC
identification of the patient's clinical history of pancreatic gastrinoma and an additional immunohistochemical
NU
stain for gastrin supported a diagnosis of metastatic gastrinoma. We report this rare case to increase awareness of metastatic neuroendocrine tumors in the breast. Multiple breast lesions and lack of expression of
MA
estrogen/progesterone hormone receptors should prompt careful review of the patient's clinical history to rule-out
AC
CE
PT
ED
metastatic neuroendocrine disease.
ACCEPTED MANUSCRIPT 1. Introduction Solid papillary carcinoma (SPC) is an uncommon primary breast cancer representing less than two percent of breast carcinomas [1]. It is characterized histologically by a solid nodular growth pattern with closely
T
opposed solid tumor nests, perivascular pseudorosettes, and thin fibrovascular cores. Tumor cells have round to
RI P
oval nuclei and finely granular chromatin. Neuroendocrine differentiation is frequent, as demonstrated by positive immunohistochemical staining for neuroendocrine markers. It is also typically strongly positive for
SC
estrogen and progesterone receptors, and negative for HER2 expression. SPC is a clinically indolent entity and
NU
currently considered carcinoma in-situ by the World Health Organization if not accompanied by a conventional invasive component [2].
MA
Gastrinoma is a well-studied neuroendocrine neoplasm that most commonly occurs in the duodenum and pancreas. It usually metastasizes to the liver or regional lymph nodes [3, 4]. We herein report a case of metastatic
ED
gastrinoma to the breast. We summarize its clinical presentation, discuss the morphologic similarities between metastatic gastrinoma and primary SPC of the breast, and provide a few points to help proper pathologic
2. Case Report
AC
2.1 Clinical History
CE
PT
differentiation of these two entities to ensure accurate diagnosis in the future.
A 59-year-old woman presented with a 1.3 x 1.3 cm hypoechoic right breast mass on routine screening mammography. An excisional biopsy of this breast mass was performed. Then, bilateral MRI imaging was performed, revealing two additional right-sided small enhancing foci (Fig. 1). A sono-guided biopsy of one of the additional lesions was performed two weeks later. 2.2 Pathological Findings The excisional specimen contained a well-circumscribed ovoid lesion measuring 1.1 x 1.1 x 0.9cm. Microscopically, it was composed of solid nests of small monotonous tumor cells (Fig. 2A). Intermediate power demonstrated that the tumor cell nests contain fibrovascular cores (Fig. 2B). High power view revealed that tumor cells have round to oval nuclei, fine chromatin, and small inconspicuous nucleoli. The mitotic rate was very low. Immunohistochemical stains showed that tumor cells were positive for chromogranin (Fig. 2C) and
ACCEPTED MANUSCRIPT synaptophysin. Tumor prognostic markers showed that tumor cells were weakly positive for estrogen receptor (Fig. 2D) and negative for progesterone receptor. The tumor had clear margins of excision. A diagnosis of SPC was rendered.
RI P
the tumor in the previous excision. A diagnosis of SPC was made.
T
The subsequent core needle biopsy of the second lesion showed a tumor morphologically identical to
At this point, the patient's clinical history of stage IV pancreatic gastrinoma was brought to the attention
SC
of the pathologists. The patient was seen in an outside institution and was diagnosed and treated for pancreatic
NU
gastrinoma with small liver metastases three years ago. The outside pancreatic gastrinoma slides were not available for review. Based on the updated clinical history, an additional immunohistochemical stain for gastrin
MA
was ordered in both the breast excision and core needle biopsy specimens. The tumor cells were diffusely and strongly positive for gastrin in both cases (Fig. 3). The pathological diagnosis was then revised to metastatic
PT
Potential mastectomy was avoided.
ED
gastrinoma. This patient was subsequently discussed in the institution's multidisciplinary breast tumor board.
3. Discussion
CE
Gastrinoma is a functional well differentiated neuroendocrine tumor that occurs most frequently in the
AC
duodenum, followed by the pancreas with a minority of tumors occurring at other sites. These tumors may result in Zollinger-Ellison Syndrome which is characterized by hypergastrinemia, gastric acid hypersecretion, peptic ulcer disease, abdominal pain, nausea, heartburn and often diarrhea [4]. Gastrinomas may occur sporadically or in the setting of multiple endocrine neoplasia 1/MEN1 (roughly 20% of individuals with gastrinomas have MEN1) [4,5]. Between 60-90% of gastrinomas are clinically malignant with metastases to the lymph nodes, liver, or other distant sites at diagnosis [5,6,7]. Pancreatic gastrinomas tend to show liver metastases (incidence of approximately 50%) more frequently than duodenal tumors [5,7]. To the best of our knowledge, this represents the first reported case of metastatic gastrinoma to the breast. There are two reports in the literature of metastatic pancreatic neuroendocrine tumor to the breast [8,9]. This case is interesting to report in that metastatic gastrinoma mimics primary SPC of the breast in morphology and immunohistochemistry. It is well established that SPC of the breast has architectural and
ACCEPTED MANUSCRIPT cytologic neuroendocrine features. It contains solid nests of tumor cells with fibrovascular cores. Tumor cells are round to oval with finely granular chromatin and inconspicuous nucleoli. It also demonstrates immunoreactivity for neuroendocrine markers including synaptophysin and chromogranin [10]. This pattern is
T
nearly identical to that seen in metastatic neuroendocrine tumors, such as the metastatic gastrinoma in our case.
RI P
Indeed, APC is considered part of the spectrum of the neuroendocrine tumor of the breast. It is speculated that SPC can act as a precursor to the exceedingly rare primary neuroendocrine neoplasm of the breast [11].
SC
Differentiation of these two entities relies heavily on clinical history. In patients with a clinical history
NU
of neuroendocrine tumor, metastasis must be excluded before making a diagnosis of primary SPC of the breast. Imaging studies are very important. In this case, the patient had multiple lesions in the breast, which is very
MA
unusual for primary SPC of the breast. It should have been a clue that this may represent a metastatic lesion. Although metastatic gastrinoma and primary solid papillary carcinoma of the breast share identical
ED
morphologic and immunohistochemical features, there are other markers that can aid proper diagnosis. Tumor cells in primary SPC of the breast show strong estrogen and progesterone receptor positivity, typically of the
PT
luminal A subtype, a feature not observed in metastatic neuroendocrine tumors [12, 13]. Retrospectively, the weak estrogen receptor and negative progesterone receptor staining in this case should have prompted concern
CE
for an entity other than primary SPC of the breast.
AC
It is important to appropriately differentiate between primary SPC of the breast and metastatic gastrinoma because of their differences in prognosis and clinical management. Pure solid papillary carcinomas are currently considered in-situ lesions by the WHO, and follow-up studies suggest an indolent clinical course [2, 14]. It is managed by surgical excision and possible anti-estrogen therapy. In contrast, metastatic gastrinomas have universal mortality, with survival usually ranging from one month to one year. Treatment for these patients involves systemic chemotherapy and palliative measures [1]. In summary, we report a case of metastatic gastrinoma to the breast mimicking primary SPC of the breast. Multiple breast lesions and the absence of strong hormone receptors staining in the tumor cells should prompt careful review of the patient's clinical history to rule out the possibility of metastatic neuroendocrine disease.
ACCEPTED MANUSCRIPT References: [1] Klimstra DS, Arnold R, Capella C, et al. Neuroendocrine neoplasms of the pancreas. In: Bosman FT, Carneiro F, Hruban RH, Theise ND, eds. WHO Classification of Tumors of the Digestive System, Lyon: IARC
T
Press; 2010, p. 322-6.
RI P
[2] Visscher D, Collins L, O'Malley F, et al. Solid papillary carcinoma. In: Lakhani S, Ellis IO, Schnitt SJ, Tan P-H, van de Vijver MJ, eds. WHO Classification of Tumors of the Breast, Lyon: IARC Press; 2012, p. 108-9.
SC
[3] Stabile BE, Morrow DJ, Pessarro E. The gastrinoma triangle: Operative implications. The Am J of Surg.
NU
1984;147(1): 25–31
[4] Morrow EH1, Norton JA. Surgical management of Zollinger-Ellison syndrome; state of the art. Surg Clin
MA
North Am. 2009;89(5):1091-103
[5] Krampitz GW, Norton JA. Current management of the Zollinger-Ellison syndrome. Adv Surg.
ED
2013;47:59-79.
[6] Grozinsky-Glasberg S, Mazeh H, Gross DJ. Clinical features of pancreatic neuroendocrine tumors. J
PT
Hepatobiliary Pancreat Sci. 2015;22(8):578-85.
[7] Nassar H, Qureshi H, Volkanadsay N, Visscher D. Clinicopathologic analysis of solid papillary carcinoma of
CE
the breast and associated invasive carcinoma. Am J Surg Pathol. 2006;30(4):501-7.
AC
[8] Treilleux I, Freyer G, Tabone E, Chassagne-Clement C, Bremond A, Bailly C. Pancreatic neuroendocrine carcinoma metastatic to the breast as part of the multiple endocrine neoplasia type 1 syndrome. Endocr Pathol. 1997;8(3): 251-258.
[9] Judson K, Argani P. Intraductal spread by metastatic islet cell tumor (well-differentiated pancreatic endocrine neoplasm) involving the breast of a child, mimicking a primary mammary carcinoma. Am J Surg Pathol. 2006;30:912-918. [10] Otsuki Y, Yamada M, Shimizu, S, et al. Solid-papillary carcinoma of the breast: clinicopathological study of 20 cases. Pathol Int. 2007;57:421-9. [11] Weigelt B, Horlings HM, Kreike B, et al. Refinement of breast cancer classification by molecular characterization of histological special types. J Pathol. 2008;216(2):141-50.
ACCEPTED MANUSCRIPT [12] Bussolati G, Badve S. Carcinomas with neuroendocrine features. In: Lakhani S, Ellis IO, Schnitt SJ, Tan PH, van de Vijver MJ, eds. WHO Classification of Tumors of the Breast, Lyon: IARC Press; 2012, p. 62-3. [13] Maluf HM, Koerner FC. Solid papillary carcinoma of the breast. A form of intraductal carcinoma of the
T
carcinoma with endocrine differentiation frequently associated with mucinous carcinoma. Am J Surg Pathol.
RI P
1995;19(11):1237-44.
[14] Nassar H, Qureshi H, Volkanadsay N, Visscher D. Clinicopathologic analysis of solid papillary carcinoma
NU
SC
of the breast and associated invasive carcinomas. Am J Surg Pathol. 2006;30(4):501-7.
Figure legends:
MA
Figure 1. Magnetic resonance imaging of the right breast, enhanced T1 high resolution isotropic volume excitation (eTHRIVE). A. Imaging demonstrates a 4.0 x 2.2 cm ovoid fluid collection in the lateral right (9:00)
ED
breast following excisional biopsy of the first lesion. B. An additional 0.5 cm ring-enhancing mass within the
PT
upper outer (11:00) right breast.
CE
Figure 2. Excisional biopsy of the first mass in the breast. A. Tumor cells grow in solid nests and separated by fibrovascular cores. Adjacent to the tumor are normal breast lobules (H&E stain, X40). B. Higher power view
AC
shows that tumor cells have round to oval nuclei, finely granular chromatin and inconspicuous nucleoli (X200). C. Immunohistochemical stain for chromogranin shows strong positivity in the tumor cells (IHC stain, x200). D. Immunohistochemical stain for estrogen receptor demonstrates focal and weak positivity in the tumor cells. Notice the strong ER positivity in the adjacent benign ducts (IHC stain, x200).
Figure 3. Immunohistochemical stain for gastrin shows strong positivity in the tumor cells (A, x40; B, x200).
NU
SC
RI P
T
ACCEPTED MANUSCRIPT
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CE
PT
ED
MA
Figure 1
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Figure 2
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PT
ED
MA
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SC
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ACCEPTED MANUSCRIPT
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ACCEPTED MANUSCRIPT
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CE
PT
ED
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Figure 3
S0046-8177(16)30123-X doi: 10.1016/j.humpath.2016.05.024 YHUPA 3931
To appear in:
Human Pathology
Received date: Revised date: Accepted date:
12 February 2016 26 April 2016 23 May 2016
Please cite this article as: Burt Michael, Madan Rashna, Fan Fang, Metastatic Gastrinoma in the Breast Mimicking Primary Solid Papillary Carcinoma, Human Pathology (2016), doi: 10.1016/j.humpath.2016.05.024
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 Metastatic Gastrinoma in the Breast Mimicking Primary Solid Papillary
T
Carcinoma.
RI P
Michael Burt BA, Rashna Madan MBBS, Fang Fan MD, PhD*
SC
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS
NU
66160
MA
* Corresponding author:
Fang Fan, MD, PhD, Department of Pathology and Laboratory Medicine, University of Kansas Medical
PT
Office phone 913-588-1184.
ED
Center, 1606 KU Hospital, 3901 Rainbow Blvd., Kansas City, KS 66160. Email: [email protected];
CE
Conflict of interest: None
AC
Funding disclosures: None
Keywords: Breast solid papillary carcinoma; Metastatic gastrinoma; neuroendocrine tumor Running title: Metastatic gastrinoma in the breast
ACCEPTED MANUSCRIPT Summary: We report a case of metastatic gastrinoma to the breast morphologically mimicking solid papillary carcinoma of the breast. A 59-year-old woman presented with a hypoechoic right breast mass that histologically revealed solid nests of small monotonous tumor cells, fibrovascular cores, and round to oval nuclei with fine
T
chromatin and small prominent nucleoli. Immunohistochemistry demonstrated chromogranin and synaptophysin
RI P
positivity. Tumor prognostic markers showed weak positivity for estrogen receptor and negativity for progesterone receptor. Although an initial diagnosis of solid papillary carcinoma was rendered, subsequent
SC
identification of the patient's clinical history of pancreatic gastrinoma and an additional immunohistochemical
NU
stain for gastrin supported a diagnosis of metastatic gastrinoma. We report this rare case to increase awareness of metastatic neuroendocrine tumors in the breast. Multiple breast lesions and lack of expression of
MA
estrogen/progesterone hormone receptors should prompt careful review of the patient's clinical history to rule-out
AC
CE
PT
ED
metastatic neuroendocrine disease.
ACCEPTED MANUSCRIPT 1. Introduction Solid papillary carcinoma (SPC) is an uncommon primary breast cancer representing less than two percent of breast carcinomas [1]. It is characterized histologically by a solid nodular growth pattern with closely
T
opposed solid tumor nests, perivascular pseudorosettes, and thin fibrovascular cores. Tumor cells have round to
RI P
oval nuclei and finely granular chromatin. Neuroendocrine differentiation is frequent, as demonstrated by positive immunohistochemical staining for neuroendocrine markers. It is also typically strongly positive for
SC
estrogen and progesterone receptors, and negative for HER2 expression. SPC is a clinically indolent entity and
NU
currently considered carcinoma in-situ by the World Health Organization if not accompanied by a conventional invasive component [2].
MA
Gastrinoma is a well-studied neuroendocrine neoplasm that most commonly occurs in the duodenum and pancreas. It usually metastasizes to the liver or regional lymph nodes [3, 4]. We herein report a case of metastatic
ED
gastrinoma to the breast. We summarize its clinical presentation, discuss the morphologic similarities between metastatic gastrinoma and primary SPC of the breast, and provide a few points to help proper pathologic
2. Case Report
AC
2.1 Clinical History
CE
PT
differentiation of these two entities to ensure accurate diagnosis in the future.
A 59-year-old woman presented with a 1.3 x 1.3 cm hypoechoic right breast mass on routine screening mammography. An excisional biopsy of this breast mass was performed. Then, bilateral MRI imaging was performed, revealing two additional right-sided small enhancing foci (Fig. 1). A sono-guided biopsy of one of the additional lesions was performed two weeks later. 2.2 Pathological Findings The excisional specimen contained a well-circumscribed ovoid lesion measuring 1.1 x 1.1 x 0.9cm. Microscopically, it was composed of solid nests of small monotonous tumor cells (Fig. 2A). Intermediate power demonstrated that the tumor cell nests contain fibrovascular cores (Fig. 2B). High power view revealed that tumor cells have round to oval nuclei, fine chromatin, and small inconspicuous nucleoli. The mitotic rate was very low. Immunohistochemical stains showed that tumor cells were positive for chromogranin (Fig. 2C) and
ACCEPTED MANUSCRIPT synaptophysin. Tumor prognostic markers showed that tumor cells were weakly positive for estrogen receptor (Fig. 2D) and negative for progesterone receptor. The tumor had clear margins of excision. A diagnosis of SPC was rendered.
RI P
the tumor in the previous excision. A diagnosis of SPC was made.
T
The subsequent core needle biopsy of the second lesion showed a tumor morphologically identical to
At this point, the patient's clinical history of stage IV pancreatic gastrinoma was brought to the attention
SC
of the pathologists. The patient was seen in an outside institution and was diagnosed and treated for pancreatic
NU
gastrinoma with small liver metastases three years ago. The outside pancreatic gastrinoma slides were not available for review. Based on the updated clinical history, an additional immunohistochemical stain for gastrin
MA
was ordered in both the breast excision and core needle biopsy specimens. The tumor cells were diffusely and strongly positive for gastrin in both cases (Fig. 3). The pathological diagnosis was then revised to metastatic
PT
Potential mastectomy was avoided.
ED
gastrinoma. This patient was subsequently discussed in the institution's multidisciplinary breast tumor board.
3. Discussion
CE
Gastrinoma is a functional well differentiated neuroendocrine tumor that occurs most frequently in the
AC
duodenum, followed by the pancreas with a minority of tumors occurring at other sites. These tumors may result in Zollinger-Ellison Syndrome which is characterized by hypergastrinemia, gastric acid hypersecretion, peptic ulcer disease, abdominal pain, nausea, heartburn and often diarrhea [4]. Gastrinomas may occur sporadically or in the setting of multiple endocrine neoplasia 1/MEN1 (roughly 20% of individuals with gastrinomas have MEN1) [4,5]. Between 60-90% of gastrinomas are clinically malignant with metastases to the lymph nodes, liver, or other distant sites at diagnosis [5,6,7]. Pancreatic gastrinomas tend to show liver metastases (incidence of approximately 50%) more frequently than duodenal tumors [5,7]. To the best of our knowledge, this represents the first reported case of metastatic gastrinoma to the breast. There are two reports in the literature of metastatic pancreatic neuroendocrine tumor to the breast [8,9]. This case is interesting to report in that metastatic gastrinoma mimics primary SPC of the breast in morphology and immunohistochemistry. It is well established that SPC of the breast has architectural and
ACCEPTED MANUSCRIPT cytologic neuroendocrine features. It contains solid nests of tumor cells with fibrovascular cores. Tumor cells are round to oval with finely granular chromatin and inconspicuous nucleoli. It also demonstrates immunoreactivity for neuroendocrine markers including synaptophysin and chromogranin [10]. This pattern is
T
nearly identical to that seen in metastatic neuroendocrine tumors, such as the metastatic gastrinoma in our case.
RI P
Indeed, APC is considered part of the spectrum of the neuroendocrine tumor of the breast. It is speculated that SPC can act as a precursor to the exceedingly rare primary neuroendocrine neoplasm of the breast [11].
SC
Differentiation of these two entities relies heavily on clinical history. In patients with a clinical history
NU
of neuroendocrine tumor, metastasis must be excluded before making a diagnosis of primary SPC of the breast. Imaging studies are very important. In this case, the patient had multiple lesions in the breast, which is very
MA
unusual for primary SPC of the breast. It should have been a clue that this may represent a metastatic lesion. Although metastatic gastrinoma and primary solid papillary carcinoma of the breast share identical
ED
morphologic and immunohistochemical features, there are other markers that can aid proper diagnosis. Tumor cells in primary SPC of the breast show strong estrogen and progesterone receptor positivity, typically of the
PT
luminal A subtype, a feature not observed in metastatic neuroendocrine tumors [12, 13]. Retrospectively, the weak estrogen receptor and negative progesterone receptor staining in this case should have prompted concern
CE
for an entity other than primary SPC of the breast.
AC
It is important to appropriately differentiate between primary SPC of the breast and metastatic gastrinoma because of their differences in prognosis and clinical management. Pure solid papillary carcinomas are currently considered in-situ lesions by the WHO, and follow-up studies suggest an indolent clinical course [2, 14]. It is managed by surgical excision and possible anti-estrogen therapy. In contrast, metastatic gastrinomas have universal mortality, with survival usually ranging from one month to one year. Treatment for these patients involves systemic chemotherapy and palliative measures [1]. In summary, we report a case of metastatic gastrinoma to the breast mimicking primary SPC of the breast. Multiple breast lesions and the absence of strong hormone receptors staining in the tumor cells should prompt careful review of the patient's clinical history to rule out the possibility of metastatic neuroendocrine disease.
ACCEPTED MANUSCRIPT References: [1] Klimstra DS, Arnold R, Capella C, et al. Neuroendocrine neoplasms of the pancreas. In: Bosman FT, Carneiro F, Hruban RH, Theise ND, eds. WHO Classification of Tumors of the Digestive System, Lyon: IARC
T
Press; 2010, p. 322-6.
RI P
[2] Visscher D, Collins L, O'Malley F, et al. Solid papillary carcinoma. In: Lakhani S, Ellis IO, Schnitt SJ, Tan P-H, van de Vijver MJ, eds. WHO Classification of Tumors of the Breast, Lyon: IARC Press; 2012, p. 108-9.
SC
[3] Stabile BE, Morrow DJ, Pessarro E. The gastrinoma triangle: Operative implications. The Am J of Surg.
NU
1984;147(1): 25–31
[4] Morrow EH1, Norton JA. Surgical management of Zollinger-Ellison syndrome; state of the art. Surg Clin
MA
North Am. 2009;89(5):1091-103
[5] Krampitz GW, Norton JA. Current management of the Zollinger-Ellison syndrome. Adv Surg.
ED
2013;47:59-79.
[6] Grozinsky-Glasberg S, Mazeh H, Gross DJ. Clinical features of pancreatic neuroendocrine tumors. J
PT
Hepatobiliary Pancreat Sci. 2015;22(8):578-85.
[7] Nassar H, Qureshi H, Volkanadsay N, Visscher D. Clinicopathologic analysis of solid papillary carcinoma of
CE
the breast and associated invasive carcinoma. Am J Surg Pathol. 2006;30(4):501-7.
AC
[8] Treilleux I, Freyer G, Tabone E, Chassagne-Clement C, Bremond A, Bailly C. Pancreatic neuroendocrine carcinoma metastatic to the breast as part of the multiple endocrine neoplasia type 1 syndrome. Endocr Pathol. 1997;8(3): 251-258.
[9] Judson K, Argani P. Intraductal spread by metastatic islet cell tumor (well-differentiated pancreatic endocrine neoplasm) involving the breast of a child, mimicking a primary mammary carcinoma. Am J Surg Pathol. 2006;30:912-918. [10] Otsuki Y, Yamada M, Shimizu, S, et al. Solid-papillary carcinoma of the breast: clinicopathological study of 20 cases. Pathol Int. 2007;57:421-9. [11] Weigelt B, Horlings HM, Kreike B, et al. Refinement of breast cancer classification by molecular characterization of histological special types. J Pathol. 2008;216(2):141-50.
ACCEPTED MANUSCRIPT [12] Bussolati G, Badve S. Carcinomas with neuroendocrine features. In: Lakhani S, Ellis IO, Schnitt SJ, Tan PH, van de Vijver MJ, eds. WHO Classification of Tumors of the Breast, Lyon: IARC Press; 2012, p. 62-3. [13] Maluf HM, Koerner FC. Solid papillary carcinoma of the breast. A form of intraductal carcinoma of the
T
carcinoma with endocrine differentiation frequently associated with mucinous carcinoma. Am J Surg Pathol.
RI P
1995;19(11):1237-44.
[14] Nassar H, Qureshi H, Volkanadsay N, Visscher D. Clinicopathologic analysis of solid papillary carcinoma
NU
SC
of the breast and associated invasive carcinomas. Am J Surg Pathol. 2006;30(4):501-7.
Figure legends:
MA
Figure 1. Magnetic resonance imaging of the right breast, enhanced T1 high resolution isotropic volume excitation (eTHRIVE). A. Imaging demonstrates a 4.0 x 2.2 cm ovoid fluid collection in the lateral right (9:00)
ED
breast following excisional biopsy of the first lesion. B. An additional 0.5 cm ring-enhancing mass within the
PT
upper outer (11:00) right breast.
CE
Figure 2. Excisional biopsy of the first mass in the breast. A. Tumor cells grow in solid nests and separated by fibrovascular cores. Adjacent to the tumor are normal breast lobules (H&E stain, X40). B. Higher power view
AC
shows that tumor cells have round to oval nuclei, finely granular chromatin and inconspicuous nucleoli (X200). C. Immunohistochemical stain for chromogranin shows strong positivity in the tumor cells (IHC stain, x200). D. Immunohistochemical stain for estrogen receptor demonstrates focal and weak positivity in the tumor cells. Notice the strong ER positivity in the adjacent benign ducts (IHC stain, x200).
Figure 3. Immunohistochemical stain for gastrin shows strong positivity in the tumor cells (A, x40; B, x200).
NU
SC
RI P
T
ACCEPTED MANUSCRIPT
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Figure 1
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Figure 2
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Figure 3