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Gastric Linitis Plastica and Peritoneal Carcinomatosis as First Manifestations of Occult Breast Carcinoma: A Case Report and Literature Review

Gastric Linitis Plastica and Peritoneal Carcinomatosis as First Manifestations of Occult Breast... Hindawi Case Reports in Oncological Medicine Volume 2018, Article ID 4714708, 4 pages https://doi.org/10.1155/2018/4714708 Case Report Gastric Linitis Plastica and Peritoneal Carcinomatosis as First Manifestations of Occult Breast Carcinoma: A Case Report and Literature Review 1,2 1 1,2 3 Mara Mantiero , Giovanni Faggioni, Alice Menichetti, Matteo Fassan, 1,2 1,2 Valentina Guarneri, and Pierfranco Conte Medical Oncology Unit 2, Istituto Oncologico Veneto, IRCCS, Padova, Italy Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy Department of Medicine, Surgical Pathology & Cytopathology Unit, University of Padova, Padova, Italy Correspondence should be addressed to Mara Mantiero; mara.mantiero@hotmail.it Received 25 February 2018; Revised 14 May 2018; Accepted 11 June 2018; Published 8 July 2018 Academic Editor: Constantine Gennatas Copyright © 2018 Mara Mantiero et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Gastric linitis plastica is a diffuse involvement of the stomach walls by neoplastic cells. It represents about 3–19% of primitive gastric adenocarcinomas, but it can also be the manifestation of a metastatic disease. Breast cancer is the most frequent malignancy in women, and the metastatic spread to the stomach occurs in less than 10% of the cases. We present an unusual case of gastric linitis plastica and peritoneal carcinomatosis as manifestations of an occult breast cancer in a 53-year-old woman. Imaging and endoscopic evaluation were not able to discriminate a primary from a secondary gastric lesion. The histological evaluation excluded the diagnosis of a primary gastric neoplasia. The IHC profile was consistent with the diagnosis of metastases from the breast cancer. Due to the hormonal receptors’ positivity, we started therapy with fulvestrant (500 mg, day 0, 14, and 28 and every 28 days thereafter by intramuscular injection). After 20 months, the same therapy is still ongoing and well tolerated, while the patient is in good condition with improvement of the dysphagia. Almost 2 years after the diagnosis of linitis plastica, the primitive breast lesion is still occult. 1. Introduction origin of the lesion was crucial to avoid a potentially useless gastric surgery. Metastatic cancer of unknown primary (CUP site syndrome) is characterized by the presence of the metastatic lesion 2. Case Presentation without the primitive carcinoma. It accounts for 3–5% of all solid malignant tumours, and the prognosis is generally In March 2016, a 53-year-old premenopausal woman was poor [1]. Only microscopic analysis, with histological and admitted to our institute with the diagnosis of gastric linitis immunohistochemical exam, can define the primary origin plastica and peritoneal carcinomatosis. She presented with of the lesion, and it is fundamental for the clinician to define upper abdominal pain, dyspepsia, nausea, and daily post- the correct treatment plan. The discussion with the patholo- prandial vomiting with weight loss of approximately 4 kilo- gist is essential. grams in 2 months. The Eastern Cooperative Oncology Metastasis from breast cancer to the gastrointestinal tract Group (ECOG) performance status (PS) was 2. Her medical is rare, less than 10% [2], and typically occurs many years history was negative for oncologic diseases, and she had no after the diagnosis. relevant comorbidities; no history of Helicobacter pylori- We present an unusual case of gastric linitis plastica and associated gastritis. At clinical examination, she presented peritoneal carcinomatosis as first manifestations of an occult with epigastric tenderness and no mass. Blood tests were breast cancer. The correct identification of the primary within the normal values, with the exception of CA15.3 2 Case Reports in Oncological Medicine (211 U/ml) and CEA (11.1 ng/ml). Abdominal computed tomography (CT) revealed an increased wall thickness of the pyloric antrum along with mesenteric lymphadenopathy (20 mm) and peritoneal carcinomatosis. No liver metastases were detected. At esophagogastroduodenoscopy (EGDS), a severe pyloric stenosis was reported in the absence of muco- sal lesions. The clinical manifestation was strongly suggestive of linitis plastica. Several gastric biopsies were performed, and histology concluded for a diffuse localization of epithelial cancer. Immunohistochemistry excluded gastrointestinal origin. There was a strong immunoreactivity for estrogen and progesterone receptors (ER-PgR: 80%-80%), GATA3 Figure 1: Histology confirmed localization of adenocarcinoma with (3+), and cytokeratin (CK) 7, 8, 18, and 19; the human epi- immunohistochemistry: ER 90%, PgR 35%, CK7 3+, GCDFP-15 3+, and HER2 1+. thelial growth factor receptor 2 (HER2) was negative (1+) and the Ki67 index was <5%. Histological exam concluded for metastatic breast cancer with gastric linitis plastica. primitive lesion prevented any possibility of the histological A complete breast radiological investigation including subdefinition, although the lobular histological subtype is bilateral ultrasound and mammography, and magnetic reso- the most common cause of metastatic gastric linitis plastica caused by breast cancer [4]. nance imaging excluded the presence of breast abnormalities. Multiple bilateral suspicious axillary lymph nodes (maxi- mum diameter of approximately 10 mm) were identified at ultrasonography and MRI. A fine-needle aspiration of a right 3. Discussion axillary lymph node was performed, and cytology was posi- tive for epithelial malignant cells. Breast cancer is the most common malignancy in women, To definitively exclude a gastrointestinal origin of the accounting for about 30% of new diagnosis. Approximately neoplasm, the patient also underwent laparoscopic perito- 6–10% of new breast cancer cases are initially metastatic, neal biopsy. Histological and immunohistochemical studies and the most common sites of metastatization are the liver, confirmed breast origin. After the multidisciplinary discus- lung, brain, and bone [5]. Metastases from breast cancer to sion, a surgical approach was excluded. A Witzel feeding jeju- the gastrointestinal tract are rare. Harris et al. published in nostomy was created. 1984 the data about an autopsy series of 109 patients who All international breast cancer guidelines recommend died from breast cancer: 84% of them were metastatic and endocrine therapy in luminal metastatic breast cancer with- only 8.8% had gastric involvement [2]. out visceral crisis. Our patient, after jejunostomy creation Typically, metastatic spread to the gastrointestinal tract and starting of enteral nutrition, was asymptomatic, and so, occurs many years after the diagnosis of breast cancer. In in April 2016, hormone therapy with fulvestrant was started our case, it was at the onset of the disease. Gastric metastati- (500 mg, day 0, 14, and 28 and every 28 days thereafter by zation can have two different patterns of manifestation: nod- intramuscular injection). We decided on intramuscular ther- ular pattern with ulcerative masses, typical of invasive ductal apy to overcome the patient’s dysphagia. carcinoma (IDC), or a diffuse mural involvement, typical of After four months of hormone therapy, CT scan was per- invasive lobular carcinoma (ILC). In the latter case, multiple formed and reported stable disease. The patient also experi- and deep biopsies are recommended for the diagnosis enced clinical improvement with weight increase (1 kg) and because sometimes the scirrhous and fibrotic reaction can palliation of dysphagia. Sporadic postprandial vomiting was invade the gastric wall without mucosal involvement. still present. Although the cases described are not many, the lobular In January 2017, CA15.3 was normalized (3.8 U/ml) and histological subtype is the most common cause of metastatic a new EGDS with biopsies was performed. Histology con- gastric linitis plastica caused by breast cancer [4]. Taal et al. firmed localization of adenocarcinoma with immunohisto- performed a retrospective analysis in a 15-year period show- chemistry ER 90%, PgR 35%, CK7 3+, gross cystic disease ing that 83% of patients with breast cancer and gastric metas- fluid protein 15 (GCDFP-15) 3+, and HER2 1+ (Figure 1). tasis have lobular histological subtype [6]. Rare cases of linitis The patient is still in a good clinical condition with plastica of the rectum as a possible clinical presentation of ECOG PS 1 up to this day. Supportive enteral nutrition is still lobular breast carcinoma are also described [7–10]. However, ongoing, but dysphagia has significantly improved. Hormone the biological mechanism underlying this unusual correla- therapy with fulvestrant is still ongoing and well tolerated. tion is not yet clear. The last radiological evaluation was performed in February The presence of the metastatic lesion without primitive 2018, and it showed a stable disease. carcinoma represents a heterogeneous group defined as “car- Additionally, because of a potential genetic correlation cinoma of unknown primary” (CUP). They account for 3– between diffuse gastric carcinoma and early-onset lobular 5% of all tumors, and the prognosis is poor [1]. Probably, breast carcinoma [3], we also performed a genetic evaluation these tumors acquire the capacity to metastasize before the and searched for CDH1 germline mutations, but no genetic development of a clinically evident primary lesion [11]. A abnormalities were identified. In our case, the absence of historical autopsy study showed that the breast was the Case Reports in Oncological Medicine 3 primary tumor site in CUP syndrome in only 2% of the cases Conflicts of Interest [12, 13]. The authors declare that there is no conflict of interest Immunohistochemistry is fundamental to correctly iden- regarding the publication of this article. tify the primary site and, in our case, was essential to decide the therapeutic strategy. Since about 80% of human breast cancer cells express hormone receptors, ER and PR statuses References are usually used as reliable markers for breast origin [14]. However, the primary gastric carcinomas can also express [1] K. Fizazi, F. A. Greco, N. Pavlidis, G. Daugaard, K. Oien, and sex hormone receptors. According to Tokunaga and col- G. Pentheroudakis, “Cancers of unknown primary site: ESMO leagues, the rates of positivity are about 26.6% for ER and Clinical Practice Guidelines for diagnosis, treatment and 20.6% for PR [15]. In a more recent analysis by Matsui follow-up,” Annals of Oncology, vol. 26, Supplement 5, et al., the positivity is about 32% and 12% for ER and PR, pp. v133–v138, 2015. respectively [16]. For this reason, their use, in association [2] M. Harris, A. Howell, M. Chrissohou, R. I. Swindell, with other supplemental diagnostic markers, can improve M. Hudson, and R. A. Sellwood, “A comparison of the meta- the diagnostic accuracy. From an IHC point of view, breast static pattern of infiltrating lobular carcinoma and infiltrating cancer is positive for CK7 and CK18 and negative for duct carcinoma of the breast,” British Journal of Cancer, vol. 50, no. 1, pp. 23–30, 1984. CK20, as our patient. CK7 and CK20 are the first steps in the IHC markers’ approach used in CUP syndrome. [3] G. Corso, M. Intra, C. Trentin, P. Veronesi, and V. Galimberti, “CDH1 germline mutations and hereditary lobular breast can- Cytoplasmatic positivity for GCDFP-15 is also highly spe- cer,” Familial Cancer, vol. 15, no. 2, pp. 215–219, 2016. cific (90%) to identify a malignant breast lesion. GCDFP- [4] B. G. Taal, H. Peterse, and H. Boot, “Clinical presentation, 15 is a marker of apocrine differentiation and is detected endoscopic features and treatment of gastric metastases from in 62–72% of breast cancers [17, 18]. breast carcinoma,” Cancer, vol. 89, no. 11, pp. 2214–2221, Probably in the future, the RNA microarray with gene expression tests will play an important role in the diagnosis [5] M. C. Cummings, P. T. Simpson, L. E. Reid et al., “Metastatic of CUP. Su et al. defines a predictive algorithm using 110 progression of breast cancer: insights from 50 years of autop- genes expressed in the 11 most frequent malignancies. In sies,” The Journal of Pathology, vol. 232, no. 1, pp. 23–31, 2014. their study, they have been able to predict the anatomical site [6] B. G. Taal, F. C. A. den Hartog Jager, R. Steinmetz, and of the tumor origin for 90% of the 175 carcinomas analyzed, H. Peterse, “The spectrum of gastrointestinal metastases of including 9 of the 12 metastatic lesions [19]. The role of RNA breast carcinoma: I. Stomach,” Gastrointestinal Endoscopy, profiling is evolving. More studies are ongoing, but the avail- vol. 38, no. 2, pp. 130–135, 1992. able data are still premature. More studies are needed to [7] F. Venturini, V. Gambi, S. Di Lernia et al., “Linitis plastica of understand if gene expression can be different between pri- the rectum as a clinical presentation of metastatic lobular mary and metastatic lesions. carcinoma of the breast,” Journal of Clinical Oncology, vol. 34, The management of metastatic linitis plastica of the no. 7, pp. e54–e56, 2016. stomach is totally different from that of primary gastric car- [8] K. Yanagisawa, M. Yamamoto, E. Ueno, and N. Ohkouchi, cinoma. Surgical resection is the first option for patients with “Synchronous rectal metastasis from invasive lobular carci- primary gastric cancer without metastasis, but, in our case, noma of the breast,” Journal of Gastroenterology and Hepatol- gastric lesion was the manifestation of a systemic disease. ogy, vol. 22, no. 4, pp. 601-602, 2007. All international breast cancer guidelines recommend endo- [9] A. J. Cano-Maldonado, M. Diaz-Tie, E. Vives-Rodriguez et al., “Rectal metastasis of lobular breast carcinoma,” Revista Espa- crine therapy in luminal metastatic breast cancer without ñola de Enfermedades Digestivas, vol. 100, no. 7, pp. 440–442, visceral crisis. For this reason, after the resolution of the symptoms with the jejunostomy creation, we decided to start [10] R. Arrangoiz, P. Papavasiliou, H. Dushkin, and J. M. Farma, systemic therapy with fulvestrant. “Case report and literature review: metastatic lobular carci- In conclusion, interaction between clinician and patholo- noma of the breast – an unusual presentation,” International gist is important to select the correct IHC tests to perform. Journal of Surgery Case Reports, vol. 2, no. 8, pp. 301–305, Our goal in this case report is twofold: firstly, to improve the knowledge of surgeons and clinicians reminding them [11] A. Kramer, G. Hubner, A. Schneeweiss, G. Folprecht, and the need to rule out the possibility of a breast origin in K. Neben, “Carcinoma of unknown primary – an orphan dis- women with gastric involvement, even in patients without a ease?,” Breast Care, vol. 3, no. 3, pp. 164–170, 2008. previous or concurrent history of breast carcinoma; secondly [12] J. L. Abbruzzese, M. C. Abbruzzese, R. Lenzi, K. R. Hess, and to increase the attention on immunohistochemical analysis. M. N. Raber, “Analysis of a diagnostic strategy for patients To our knowledge, our case is the first published paper on with suspected tumors of unknown origin,” Journal of Clinical CUP syndrome of breast cancer with this peculiar type of Oncology, vol. 13, no. 8, pp. 2094–2103, 1995. presentation. This case could be helpful with other clinicians [13] T. Le Chevalier, E. Cvitkovic, P. Caille et al., “Early metastatic due to its rarity and its unusual outcome. cancer of unknown primary origin at presentation. A clinical study of 302 consecutive autopsied patients,” Archives of Inter- nal Medicine, vol. 148, no. 9, pp. 2035–2039, 1988. Abbreviations [14] L. de Decker, M. Campone, F. Retornaz et al., “Association CUP: Carcinoma of unknown primary. between oestrogens receptor expressions in breast cancer and 4 Case Reports in Oncological Medicine comorbidities: a cross-sectional, population-based study,” PLoS One, vol. 9, no. 5, article e98127, 2014. [15] A. Tokunaga, K. Nishi, N. Matsukura et al., “Estrogen and progesterone receptors in gastric cancer,” Cancer, vol. 57, no. 7, pp. 1376–1379, 1986. [16] M. Matsui, O. Kojima, S. Kawakami, Y. Uehara, and T. Takahashi, “The prognosis of patients with gastric cancer possessing sex hormone receptors,” Surgery Today, vol. 22, no. 5, pp. 421–425, 1992. [17] O. Kaufmann, T. Deidesheimer, M. Muehlenberg, P. Deicke, and M. Dietel, “Immunohistochemical differentiation of meta- static breast carcinomas from metastatic adenocarcinomas of other common primary sites,” Histopathology, vol. 29, no. 3, pp. 233–240, 1996. [18] M. R. Wick, T. J. Lillemoe, G. T. Copland, P. E. Swanson, J. C. Manivel, and D. T. Kiang, “Gross cystic disease fluid protein-15 as a marker for breast cancer: immunohisto- chemical analysis of 690 human neoplasms and comparison with alpha-lactalbumin,” Human Pathology, vol. 20, no. 3, pp. 281–287, 1989. [19] A. I. Su, J. B. Welsh, L. M. Sapinoso et al., “Molecular classifi- cation of human carcinomas by use of gene expression signa- tures,” Cancer Research, vol. 61, no. 20, pp. 7388–7393, 2001. 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Gastric Linitis Plastica and Peritoneal Carcinomatosis as First Manifestations of Occult Breast Carcinoma: A Case Report and Literature Review

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Hindawi Case Reports in Oncological Medicine Volume 2018, Article ID 4714708, 4 pages https://doi.org/10.1155/2018/4714708 Case Report Gastric Linitis Plastica and Peritoneal Carcinomatosis as First Manifestations of Occult Breast Carcinoma: A Case Report and Literature Review 1,2 1 1,2 3 Mara Mantiero , Giovanni Faggioni, Alice Menichetti, Matteo Fassan, 1,2 1,2 Valentina Guarneri, and Pierfranco Conte Medical Oncology Unit 2, Istituto Oncologico Veneto, IRCCS, Padova, Italy Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy Department of Medicine, Surgical Pathology & Cytopathology Unit, University of Padova, Padova, Italy Correspondence should be addressed to Mara Mantiero; mara.mantiero@hotmail.it Received 25 February 2018; Revised 14 May 2018; Accepted 11 June 2018; Published 8 July 2018 Academic Editor: Constantine Gennatas Copyright © 2018 Mara Mantiero et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Gastric linitis plastica is a diffuse involvement of the stomach walls by neoplastic cells. It represents about 3–19% of primitive gastric adenocarcinomas, but it can also be the manifestation of a metastatic disease. Breast cancer is the most frequent malignancy in women, and the metastatic spread to the stomach occurs in less than 10% of the cases. We present an unusual case of gastric linitis plastica and peritoneal carcinomatosis as manifestations of an occult breast cancer in a 53-year-old woman. Imaging and endoscopic evaluation were not able to discriminate a primary from a secondary gastric lesion. The histological evaluation excluded the diagnosis of a primary gastric neoplasia. The IHC profile was consistent with the diagnosis of metastases from the breast cancer. Due to the hormonal receptors’ positivity, we started therapy with fulvestrant (500 mg, day 0, 14, and 28 and every 28 days thereafter by intramuscular injection). After 20 months, the same therapy is still ongoing and well tolerated, while the patient is in good condition with improvement of the dysphagia. Almost 2 years after the diagnosis of linitis plastica, the primitive breast lesion is still occult. 1. Introduction origin of the lesion was crucial to avoid a potentially useless gastric surgery. Metastatic cancer of unknown primary (CUP site syndrome) is characterized by the presence of the metastatic lesion 2. Case Presentation without the primitive carcinoma. It accounts for 3–5% of all solid malignant tumours, and the prognosis is generally In March 2016, a 53-year-old premenopausal woman was poor [1]. Only microscopic analysis, with histological and admitted to our institute with the diagnosis of gastric linitis immunohistochemical exam, can define the primary origin plastica and peritoneal carcinomatosis. She presented with of the lesion, and it is fundamental for the clinician to define upper abdominal pain, dyspepsia, nausea, and daily post- the correct treatment plan. The discussion with the patholo- prandial vomiting with weight loss of approximately 4 kilo- gist is essential. grams in 2 months. The Eastern Cooperative Oncology Metastasis from breast cancer to the gastrointestinal tract Group (ECOG) performance status (PS) was 2. Her medical is rare, less than 10% [2], and typically occurs many years history was negative for oncologic diseases, and she had no after the diagnosis. relevant comorbidities; no history of Helicobacter pylori- We present an unusual case of gastric linitis plastica and associated gastritis. At clinical examination, she presented peritoneal carcinomatosis as first manifestations of an occult with epigastric tenderness and no mass. Blood tests were breast cancer. The correct identification of the primary within the normal values, with the exception of CA15.3 2 Case Reports in Oncological Medicine (211 U/ml) and CEA (11.1 ng/ml). Abdominal computed tomography (CT) revealed an increased wall thickness of the pyloric antrum along with mesenteric lymphadenopathy (20 mm) and peritoneal carcinomatosis. No liver metastases were detected. At esophagogastroduodenoscopy (EGDS), a severe pyloric stenosis was reported in the absence of muco- sal lesions. The clinical manifestation was strongly suggestive of linitis plastica. Several gastric biopsies were performed, and histology concluded for a diffuse localization of epithelial cancer. Immunohistochemistry excluded gastrointestinal origin. There was a strong immunoreactivity for estrogen and progesterone receptors (ER-PgR: 80%-80%), GATA3 Figure 1: Histology confirmed localization of adenocarcinoma with (3+), and cytokeratin (CK) 7, 8, 18, and 19; the human epi- immunohistochemistry: ER 90%, PgR 35%, CK7 3+, GCDFP-15 3+, and HER2 1+. thelial growth factor receptor 2 (HER2) was negative (1+) and the Ki67 index was <5%. Histological exam concluded for metastatic breast cancer with gastric linitis plastica. primitive lesion prevented any possibility of the histological A complete breast radiological investigation including subdefinition, although the lobular histological subtype is bilateral ultrasound and mammography, and magnetic reso- the most common cause of metastatic gastric linitis plastica caused by breast cancer [4]. nance imaging excluded the presence of breast abnormalities. Multiple bilateral suspicious axillary lymph nodes (maxi- mum diameter of approximately 10 mm) were identified at ultrasonography and MRI. A fine-needle aspiration of a right 3. Discussion axillary lymph node was performed, and cytology was posi- tive for epithelial malignant cells. Breast cancer is the most common malignancy in women, To definitively exclude a gastrointestinal origin of the accounting for about 30% of new diagnosis. Approximately neoplasm, the patient also underwent laparoscopic perito- 6–10% of new breast cancer cases are initially metastatic, neal biopsy. Histological and immunohistochemical studies and the most common sites of metastatization are the liver, confirmed breast origin. After the multidisciplinary discus- lung, brain, and bone [5]. Metastases from breast cancer to sion, a surgical approach was excluded. A Witzel feeding jeju- the gastrointestinal tract are rare. Harris et al. published in nostomy was created. 1984 the data about an autopsy series of 109 patients who All international breast cancer guidelines recommend died from breast cancer: 84% of them were metastatic and endocrine therapy in luminal metastatic breast cancer with- only 8.8% had gastric involvement [2]. out visceral crisis. Our patient, after jejunostomy creation Typically, metastatic spread to the gastrointestinal tract and starting of enteral nutrition, was asymptomatic, and so, occurs many years after the diagnosis of breast cancer. In in April 2016, hormone therapy with fulvestrant was started our case, it was at the onset of the disease. Gastric metastati- (500 mg, day 0, 14, and 28 and every 28 days thereafter by zation can have two different patterns of manifestation: nod- intramuscular injection). We decided on intramuscular ther- ular pattern with ulcerative masses, typical of invasive ductal apy to overcome the patient’s dysphagia. carcinoma (IDC), or a diffuse mural involvement, typical of After four months of hormone therapy, CT scan was per- invasive lobular carcinoma (ILC). In the latter case, multiple formed and reported stable disease. The patient also experi- and deep biopsies are recommended for the diagnosis enced clinical improvement with weight increase (1 kg) and because sometimes the scirrhous and fibrotic reaction can palliation of dysphagia. Sporadic postprandial vomiting was invade the gastric wall without mucosal involvement. still present. Although the cases described are not many, the lobular In January 2017, CA15.3 was normalized (3.8 U/ml) and histological subtype is the most common cause of metastatic a new EGDS with biopsies was performed. Histology con- gastric linitis plastica caused by breast cancer [4]. Taal et al. firmed localization of adenocarcinoma with immunohisto- performed a retrospective analysis in a 15-year period show- chemistry ER 90%, PgR 35%, CK7 3+, gross cystic disease ing that 83% of patients with breast cancer and gastric metas- fluid protein 15 (GCDFP-15) 3+, and HER2 1+ (Figure 1). tasis have lobular histological subtype [6]. Rare cases of linitis The patient is still in a good clinical condition with plastica of the rectum as a possible clinical presentation of ECOG PS 1 up to this day. Supportive enteral nutrition is still lobular breast carcinoma are also described [7–10]. However, ongoing, but dysphagia has significantly improved. Hormone the biological mechanism underlying this unusual correla- therapy with fulvestrant is still ongoing and well tolerated. tion is not yet clear. The last radiological evaluation was performed in February The presence of the metastatic lesion without primitive 2018, and it showed a stable disease. carcinoma represents a heterogeneous group defined as “car- Additionally, because of a potential genetic correlation cinoma of unknown primary” (CUP). They account for 3– between diffuse gastric carcinoma and early-onset lobular 5% of all tumors, and the prognosis is poor [1]. Probably, breast carcinoma [3], we also performed a genetic evaluation these tumors acquire the capacity to metastasize before the and searched for CDH1 germline mutations, but no genetic development of a clinically evident primary lesion [11]. A abnormalities were identified. In our case, the absence of historical autopsy study showed that the breast was the Case Reports in Oncological Medicine 3 primary tumor site in CUP syndrome in only 2% of the cases Conflicts of Interest [12, 13]. The authors declare that there is no conflict of interest Immunohistochemistry is fundamental to correctly iden- regarding the publication of this article. tify the primary site and, in our case, was essential to decide the therapeutic strategy. Since about 80% of human breast cancer cells express hormone receptors, ER and PR statuses References are usually used as reliable markers for breast origin [14]. However, the primary gastric carcinomas can also express [1] K. Fizazi, F. A. Greco, N. Pavlidis, G. Daugaard, K. Oien, and sex hormone receptors. According to Tokunaga and col- G. Pentheroudakis, “Cancers of unknown primary site: ESMO leagues, the rates of positivity are about 26.6% for ER and Clinical Practice Guidelines for diagnosis, treatment and 20.6% for PR [15]. In a more recent analysis by Matsui follow-up,” Annals of Oncology, vol. 26, Supplement 5, et al., the positivity is about 32% and 12% for ER and PR, pp. v133–v138, 2015. respectively [16]. For this reason, their use, in association [2] M. Harris, A. Howell, M. Chrissohou, R. I. Swindell, with other supplemental diagnostic markers, can improve M. Hudson, and R. A. Sellwood, “A comparison of the meta- the diagnostic accuracy. From an IHC point of view, breast static pattern of infiltrating lobular carcinoma and infiltrating cancer is positive for CK7 and CK18 and negative for duct carcinoma of the breast,” British Journal of Cancer, vol. 50, no. 1, pp. 23–30, 1984. CK20, as our patient. CK7 and CK20 are the first steps in the IHC markers’ approach used in CUP syndrome. [3] G. Corso, M. Intra, C. Trentin, P. Veronesi, and V. Galimberti, “CDH1 germline mutations and hereditary lobular breast can- Cytoplasmatic positivity for GCDFP-15 is also highly spe- cer,” Familial Cancer, vol. 15, no. 2, pp. 215–219, 2016. cific (90%) to identify a malignant breast lesion. GCDFP- [4] B. G. Taal, H. Peterse, and H. Boot, “Clinical presentation, 15 is a marker of apocrine differentiation and is detected endoscopic features and treatment of gastric metastases from in 62–72% of breast cancers [17, 18]. breast carcinoma,” Cancer, vol. 89, no. 11, pp. 2214–2221, Probably in the future, the RNA microarray with gene expression tests will play an important role in the diagnosis [5] M. C. Cummings, P. T. Simpson, L. E. Reid et al., “Metastatic of CUP. Su et al. defines a predictive algorithm using 110 progression of breast cancer: insights from 50 years of autop- genes expressed in the 11 most frequent malignancies. In sies,” The Journal of Pathology, vol. 232, no. 1, pp. 23–31, 2014. their study, they have been able to predict the anatomical site [6] B. G. Taal, F. C. A. den Hartog Jager, R. Steinmetz, and of the tumor origin for 90% of the 175 carcinomas analyzed, H. Peterse, “The spectrum of gastrointestinal metastases of including 9 of the 12 metastatic lesions [19]. The role of RNA breast carcinoma: I. Stomach,” Gastrointestinal Endoscopy, profiling is evolving. More studies are ongoing, but the avail- vol. 38, no. 2, pp. 130–135, 1992. able data are still premature. More studies are needed to [7] F. Venturini, V. Gambi, S. Di Lernia et al., “Linitis plastica of understand if gene expression can be different between pri- the rectum as a clinical presentation of metastatic lobular mary and metastatic lesions. carcinoma of the breast,” Journal of Clinical Oncology, vol. 34, The management of metastatic linitis plastica of the no. 7, pp. e54–e56, 2016. stomach is totally different from that of primary gastric car- [8] K. Yanagisawa, M. Yamamoto, E. Ueno, and N. Ohkouchi, cinoma. Surgical resection is the first option for patients with “Synchronous rectal metastasis from invasive lobular carci- primary gastric cancer without metastasis, but, in our case, noma of the breast,” Journal of Gastroenterology and Hepatol- gastric lesion was the manifestation of a systemic disease. ogy, vol. 22, no. 4, pp. 601-602, 2007. All international breast cancer guidelines recommend endo- [9] A. J. Cano-Maldonado, M. Diaz-Tie, E. Vives-Rodriguez et al., “Rectal metastasis of lobular breast carcinoma,” Revista Espa- crine therapy in luminal metastatic breast cancer without ñola de Enfermedades Digestivas, vol. 100, no. 7, pp. 440–442, visceral crisis. For this reason, after the resolution of the symptoms with the jejunostomy creation, we decided to start [10] R. Arrangoiz, P. Papavasiliou, H. Dushkin, and J. M. 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