Gastro-intestinal symptoms as clinical manifestation of peritoneal and retroperitoneal spread of an invasive lobular breast cancer: report of a case and review of the literature

G Franceschini 1 A Manno 1 A Mul 0 A Verbo 1 G Rizzo 1 D Sermoneta 1 L Petito 1 P D'alba 1 C Maggiore 0 D Terribile 1 R Masetti 1 C Coco 1 0 Dept of Pathology, Universita Cattolica del Sacro Cuore , Rome , Italy 1 Dept of Surgery, Universita Cattolica del Sacro Cuore , Rome , Italy Background: Distant spread from breast cancer is commonly found in bones, lungs, liver and central nervous system. Metastatic involvement of peritoneum and retroperitoneum is unusual and unexpected. Case presentation: We report the case of a 67 year-old-woman who presented with gastrointestinal symptoms which revealed to be the clinical manifestations of peritoneal and retroperitoneal metastatic spread of an invasive lobular breast cancer diagnosed 15 years before. Conclusion: To the best of our knowledge, the case presented is the third one reported in literature showing a wide peritoneal and extraperitoneal diffusion of an invasive lobular breast cancer. The long and complex diagnostic work up which led us to the diagnosis is illustrated, with particular emphasis on the multidisciplinary approach, which is mandatory to obtain such a result in these cases. Awareness of such a condition by clinicians is mandatory in order to make an early diagnosis and start a prompt and correct therapeutic approach. - Background Invasive lobular breast cancer (ILC) takes origin in the milk-producing glands of the breast and is the most common histological breast cancer after the ductal carcinoma (DC), accounting for 814% of cases [1]. The typical histologic picture is characterized by small, regular, noncohesive cells arranged in the so called "Indian file" appearance [2]; the neoplastic cells infiltrate the parenchyma around non-neoplastic ducts, inducing little connective tissue response [3]. Being physical examination and mammography often non-specific, contrastenhanced magnetic resonance imaging (MRI) represents the gold standard for a correct diagnosis [4]. ILC has a higher tendency than DC to be multi-focal and bilateral [5]. Also the pattern of metastatic spread differs significantly between these 2 kinds of breast tumours, with a more common occurrence of unusual location of distant neoplastic foci, especially in the gastrointestinal tract, the genitourinary system and the peritoneum or retroperitoneum, secondary to ILC. This event is unexpected, usually with a long interval after the initial diagnosis of ILC, and the presenting symptoms as well as the endoscopic and the radiographic pictures are often non-specific. These conditions lead to a frequent delay in diagnosis which prevents the prompt starting of systemic treatment necessary to obtain a good control of symptoms. The case reported gives an example of this unusual metastatic diffusion and of the complex diagnostic work up which led us to he diagnosis. Case presentation A 67-year-old woman underwent right modified radical mastectomy and axillary lymph node dissection for carcinoma of the breast 15 years ago. Histological examination of the tumour revealed a 4 cm invasive lobular carcinoma of histological grade 2. Two of the 20 lymph nodes examined were infiltrated by tumour cells. Immunohistochemistry for oestrogen and progesterone receptors showed weak staining of 20% of cancer cells for both receptors. There was no evidence of distant metastases at the time of diagnosis. The patient received six cycles of adjuvant chemotherapy (cyclophosphamide 500 mg/m2, mitoxantrone 10 mg/m2, 5-fluorouracil 500 mg/m2, every 21 days) and was on tamoxifen. Ten years later a local recurrence occurred, and the patient underwent partial resection of the thorax wall followed by reconstruction by transverse rectus abdominis musculocutaneus (TRAM) flap technique. No adjuvant treatment was given. The patient came to our attention complaining of a 4-month history of diffuse abdominal pain associated to constipation, tenesmus and sporadic rectal bleeding. On physical examination, the patient was pale but moderately nourished. The mastectomy bed, the controlateral breast, and both axilla were normal. Abdominal examination showed no palpable mass or ascites. At digital examination the rectum appeared stenotic from about 6 cm above the anal verge, but without evidence of endoluminal masses. Haematological analysis and biochemical parameters including liver and renal function tests were within the normal range. The urine cytology revealed micro-hematuria. The patient was submitted to a rectosigmoidoscopy which showed a diffuse thickening of the anterior wall of the rectum, which determined mild stenosis beginning 7 cm above the anal verge, without evidence of endoluminal masses. The mucosa which lined the anterior rectal wall was hyperaemic and easily bleeding. The posterior wall of the vagina showed diffuse thickening at vaginal endoscopy. The histological examination of multiple biopsies taken during rectosigmoidoscopy, revealed an extensive infiltration by scarcely cohesive neoplastic cells with "Indian file" features and focal targettoid arrangement around rectal glands (Fig 1, 2). The vaginal biopsy confirmed a prevalent "Indian file" neoplastic growth pattern (Fig. 3). In both biopsies malignant cells were small, with atypical nuclei and vacuolated cytoplasm, often with "signet ring" morphology. The rectal glands and the vaginal epithelium showed no atypias A panel of selected immunohistochemical markers was used to confirm the metastatic nature of the neoplastic mass and its site of origin. Immunohistochemical stainings for oestrogen and progesterone receptors (Fig 4), GFCDP-15, C-ERB-B2 and CK 7 were positive. Otherwise, they resulted negative for CK 20, WT-1, CA-125 and CDX-2. This immunohistochemical pattern, together with the typical morphological picture showed above, let us confirm the diagnosis of metastatic location from ILC. A computerised tomography (CT) scan of the abdomen and pelvis showed how the pelvic cavity was almost completely occupied by neoplastic tissue which infiltrated the rectal wall, causing marked stenosis, both the ovaries, the fundus of the vagina and the left lateral wall of the bladder, with involvement of the left ureter and concurrent hydronephrosis. Multiple enlarged lymph-nodes were identified in the perirectal fat, along the common iliac artery and the obturator chain and in the inter-aortocaval space. The liver and the chest appeared normal. Mammographic and ultrasonographic picture of the left breast and of both axilla were normal. On the basis of the diagnosis of wide peritoneal and extraperitoneal metastatic spread of ILC, the patient entered a protocol of systemic chemotherapy and hormonal therapy after the placement of a J ureteral stent to pass through the stenosis evidenced by the CT scan and confirmed by cystoscopy. Discsussion It is well known that the pattern of metastatic spread differs dramatically between ductal and lobular breast cancer [6,7]. In particular, the retrospective series by Borst et a (...truncated)