Acute appendicitis secondary to metastatic carcinoma of the breast: Case report and review of the literature

Acute appendicitis secondary to metastatic carcinoma of the breast: Case report and review of the literature

Cancer Treatment Communications (2015) 4, 41–45 Acute appendicitis secondary to metastatic carcinoma of the breast: Case report and review of the lit...

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Cancer Treatment Communications (2015) 4, 41–45

Acute appendicitis secondary to metastatic carcinoma of the breast: Case report and review of the literature Rie K. Taharaa, Abhishek Keraliyab, Nikhil H. Ramaiyab, Lauren L. Ritterhousec, Eric P. Winera, Sara M. Tolaneya,n a

Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA b Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA c Department of Pathology, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA Received 11 March 2015; received in revised form 17 April 2015; accepted 20 April 2015

1.

KEYWORDS

Abstract

Breast cancer; Acute appendicitis; Magnetic resonance image (MRI); Pathology; Abdominal pain; Metastatic breast cancer

A 39-year-old woman presented with abdominal pain 6 years after her diagnosis of HER2 positive breast cancer. Imaging revealed an enlarged appendix likely representing acute appendicitis. Surgery was performed, and pathological analysis of the appendix indicated metastatic carcinoma. On reviewing the literature, we found a few reported cases of appendicitis caused by metastatic carcinoma of the breast. The possibility of metastasis to the appendix must be considered in the diagnosis of right lower quadrant pain in patients with breast cancer. & 2015 Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction

We present an unusual case of a patient with acute appendicitis secondary to metastatic breast cancer. By reviewing the literature, we found a few reported cases of appendicitis due to metastatic carcinoma of the breast.

Abbreviations: MRI, magnetic resonance image; ER, estrogenreceptor; PR, progesterone-receptor; AC, doxorubicin and cyclophophamide; SATs, secondary appendiceal tumors; GI, gastrointestinal; ILC, invasive lobular carcinoma; IDC, invasive ductal carcinoma n Corresponding author. Tel.: +1 617 632 2335. E-mail address: [email protected] (S.M. Tolaney).

2.

Case report

A 39-year-old female had developed pelvic pain over the past 2 months, presenting as suprapubic discomfort and experienced moderate pressure when defecating, which was attributed to chronic constipation. The pain worsened; therefore, she contacted her primary care physician. A pelvic ultrasound demonstrated bilateral hypoechoic masses immediately adjacent to the ovaries and the uterus, possibly representing fibroids. It was difficult to identify a connection between the uterus and these masses; therefore, a pelvic magnetic resonance image (MRI) was performed. It revealed an enlarged appendix with irregular wall enhancement and surrounding inflammatory changes likely

http://dx.doi.org/10.1016/j.ctrc.2015.04.001 2213-0896/& 2015 Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

42 representing acute appendicitis (Figure 1). She was admitted for surgery for further evaluation. The patient had a history of breast cancer diagnosed 6 years prior to admission (Table 1). She initially presented with nipple inversion and a new left breast mass while breast feeding. Imaging revealed a 7-cm left breast mass, and an ultrasound-guided biopsy revealed a poorly differentiated invasive ductal carcinoma that was estrogen-receptor (ER)-positive, progesterone-receptor (PR)-positive, and HER2 -positive. She had received neoadjuvant chemotherapy with paclitaxel and trastuzumab and had undergone a mastectomy with an axillary dissection; pathology from her surgery demonstrated residual poorly differentiated carcinoma with apocrine features and focal mucin production within the 7.5-cm tumor bed, and 7/8 lymph nodes were positive. The patient received postoperative doxorubicin and cyclophophamide (AC) for four cycles followed by postmastectomy radiation therapy. She then chose to enroll in a clinical trial

R.K. Tahara et al. for patients who had residual disease after preoperative chemotherapy. She received capecitabine and bevacizumab in combination with trastuzumab and subsequently tamoxifen. She developed a chest wall recurrence while on tamoxifen. This area was fully excised, and her treatment was switched from tamoxifen to leuprolide in combination with letrozole. She remained on hormonal therapy at the time of her presentation with pelvic pain. While in the emergency room, her pulse was regular at 91 beats/min, blood pressure was 110/66 mmHg, and her temperature was 36.9 1C. She showed no signs of nausea or other constitutional symptoms. Abdomen was soft and minimally tender in the right lower quadrant but not distended. There was hard stool in the rectal vault, but no masses or gross blood in the stool. Results of laboratory analyses were normal with a normal white blood cell count. The patient was taken to the operating room for a laparoscopic appendectomy. The appendix with an inflamed

Figure 1 Magnetic resonance (MR) images of the pelvis. (A) Coronal T2-weighted MR image of the pelvis shows thickened appendix in the pelvis (arrow). (B) Axial contrast-enhanced fat saturated T1-weighted MR image of the pelvis shows irregular wall enhancement involving tip (arrow) and body (arrowhead) of appendix.

Acute appendicitis secondary to metastatic carcinoma of the breast

Table 1

Timelines of the patient treatment.

tip was identified in the pelvis. In addition, unusual white serosal implants and peritoneal studding were noted in the pelvis. A nodule in the pelvic peritoneum was excised. The postoperative course was uneventful. Pathological analysis of the appendix and peritoneum was consistent with metastatic poorly differentiated carcinoma, with focal mucin production that was morphologically consistent with the patient's primary breast carcinoma, involving the periappendiceal adipose tissue, appendix, and peritoneal nodule (Figure 2). The tumor was ER(–), PR(–), and HER2 positive(3+). She initiated treatment with docetaxel in combination with trastuzumab and pertuzumab.

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Discussion

Recurrence of HER2 + breast cancer has become less common after adjuvant trastuzumab-based therapy; however, some cases still occur. The most common sites of metastatic breast cancer include the regional nodes, bones, liver, lung, brain, and skin. Metastatic breast cancer presenting as acute appendicitis is rare, and a review of the literature reveals 12 documented cases (Table 2) [1–11]. In 1946, Oldfield reported the first case [1]. The appendix was the first site where metastases were observed in 7/12 cases and perforation was observed in half of these cases. Although primary adenocarcinoma of the appendix is possible, metastatic involvement of the appendix is rare. A review of the literature revealed 30 documented cases of carcinoma metastasizing to the appendix, of which the breast was the primary site in 12 cases. The appendix was inflamed in only five of these patients [4]. In another review of 7759

surgically removed appendices, 180 cases represented appendiceal malignancies; among these, 139 cases (1.7%) were secondary appendiceal tumors (SATs). The ovary was the most common primary origin, followed by the colon and stomach. There were no cases arising from breast cancer. Complete resection of SATs had no influence on survival [12]. Autopsy studies have demonstrated that 8–16% of breast cancer patients develop metastases in the gastrointestinal (GI) system [13,14]. The largest case series in the medical literature reporting on GI metastases secondary to breast cancer was published in 1968 by Asch et al. This autopsy series reported that the incidence of GI metastasis secondary to breast cancer is 16.4% (52 cases in 337 patients who died of breast carcinoma). The distribution of these metastases was as follows: esophagus (25%), stomach (25%), small intestine (28%), colon (19%), and rectum (4%). A total of 30.7% of those with gastrointestinal metastases had multiple metastatic deposits in the alimentary tract; 22% of these patients were symptomatic. There was no mention of the primary histological subtype in this series and no cases involved the appendix [13]. Elisabeth et al. reviewed 73 patients with gastrointestinal metastasis from breast cancer. The sites of gastrointestinal metastases included the esophagus (8%), stomach (28%), small intestine (19%), and colon and rectum (45%). Invasive lobular carcinoma (ILC) represented 34 (64%) of the 53 cases of gastrointestinal metastases. GI metastases in patients with ILC outnumbered those found in patients with invasive ductal carcinoma (IDC) by two-fold [15]. Despite the much higher prevalence of IDC among women with breast cancer, the proportion of ILC in GI metastases is 57–94%, and higher than IDC in all these reports [15–20]. The median overall survival after the

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R.K. Tahara et al. diagnosis of GI metastasis is consistent with the median survival of all women with metastatic disease secondary to breast cancer. Surgical intervention did not significantly extend the overall survival and should be considered palliative [15]. Adenocarcinoma metastasis to the appendix is an interesting infrequent finding and is important because it can cause appendicitis, commonly presenting late with a high risk of perforation [3]. Factors contributing to this late presentation of appendicitis due to metastatic carcinoma to the appendix may be the local effect of carcinoma on the intrinsic capability of the appendix to contain suppuration [7], or the masking of symptoms with intermittent steroid or cytotoxic therapy, which is a part of cancer treatment [7]. Metastatic lesions to the appendix begin as serosal implants and progressively encroach on the lumen, producing obstructive appendicitis. These lesions may remain unnoticed for some time before complete obstruction and inflammation supervene [3]. Obstruction of the small appendiceal lumen predisposes to acute inflammation and even perforation [5]. Pathologically, most cases reported have shown a similar microscopic picture. The findings include a normal mucosa with the infiltration of metastatic tumor cells into the submucosa, muscularis mucosa, and subserosa, causing a markedly constricted appendiceal lumen with the presence of an acute inflammatory process distal to the point of obstruction [2]. The clinical signs of appendicitis due to carcinoma metastases may be confused with any other type of appendicitis. The main differential diagnosis includes acute appendicitis, malignant intestinal obstruction and perforation of the bowel, and neutropenic enterocolitis. Histopathological and immunohistochemical comparison of the primary breast cancer and appendicitis site is important for diagnosis. Diagnosis is often difficult because of a prolonged disease-free interval before metastatic presentation. For cancer patients receiving chemotherapy and steroids, evaluation of right lower quadrant abdominal discomfort may be difficult. The signs and symptoms might differ from those of non-cancerous patients [8]. Our patient was receiving hormone therapy for metastatic breast cancer and was not immunosuppressed. Acute appendicitis was suspected by MRI prior to the operation. The pathological diagnosis was metastatic breast cancer to the appendix, which was invasive ductal (not lobular) carcinoma.

4.

Figure 2 Microscopic image of the tumor in appendix. (A) Low power (2  ): Appendiceal cross-section demonstrating serosal deposit of tumor. (B) Medium power (10  ): Appendiceal crosssection demonstrating poorly differentiated tumor cells transmurally infiltrating to the appendiceal mucosa. (C) High power (20  ) view: Metastatic poorly differentiated carcinoma with focal mucin production.

Conclusion

The possibility of metastasis to the appendix must be considered in the diagnosis of the right lower quadrant pain in patients with breast cancer. The intrinsic nature of malignant metastases in the appendix, with or without concurrent immunosuppressive chemotherapy, may lead to the late presentation of appendicitis with a high risk of perforation.

Conflicts of interest None. No funding received.

Acute appendicitis secondary to metastatic carcinoma of the breast

Table 2

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Reports of acute appendicitis secondary to metastatic breast carcinoma.

Authors

Age Time after cancer diagnosis

Clinical condition

Cancer therapy

Perforation Pathology

Oldfield (1946) [1]

40

3 years

NA

Perforated Ductal

Capper and Cheek 36 (1956) [2] Latchis and Canter 45 (1966) [3] Burney R.E. (1974) [4] 35

1 years

No known metastases No known metastases Stage IV

NA

NA

Chemotherapy

NA

73

3 years

Adjuvant hormone and chemotherapy NA

Perforated NA

Solis et al. (1986) [5] 60

5 years

NA

NA

Halliday (1987) [6] Maddox (1990) [7] Philippart et al. (2000) [8] Varga et al. (2005) [9] Pigolkin et al. (2008) [10] Dirksen et al. (2010) [11]

57 65 37

NA 5 years NA

NA Hormone therapy Adjuvant chemotherapy

NA NA NA Ductal Perforated NA

45 60

NA 18 year

NA NA

Perforated Ductal NA NA

76

NA

NA

Perforated Lobular

6 years 16 months

No known metastases No known metastases No known metastases Primary Stage IV No known metastases Primary No known metastases Primary

NA

Ductal and lobular Perforated NA

Squamous

NA=Not applicable.

Written informed consent was obtained from the patient for publication of this case report and the accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

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