Metastatic breast cancer manifested as refractory anemia and gastric polyps.ABSTRACT
Gastric metastasis from breast cancer is uncommon and typically occurs in patients with disseminated disease. The vast majority of patients with gastric lesions have a known preexisting pre·ex·ist or pre-ex·ist
v. pre·ex·ist·ed, pre·ex·ist·ing, pre·ex·ists
To exist before (something); precede: Dinosaurs preexisted humans.
v.intr. diagnosis of breast cancer. In contrast, we describe a case in which a minimal breast cancer minimal breast cancer Oncology An invasive breast CA measuring ≤ 5 mm. See Breast cancer. was found to be the primary tumor during the workup work·up
n. Abbr. w/u
A thorough medical examination for diagnostic purposes. of a patient first diagnosed with carcinoma of unknown primary and subsequently presumed to have metastatic gastric cancer. Our case illustrates that a diagnosis of breast cancer metastatic to the stomach may require a high index of suspicion index of suspicion Medtalk A phrase broadly used to indicate how seriously a particular disease is being entertained as a diagnosis; as an example, there is a high IOS that rapid and unexplained weight loss in an elderly Pt is due to pancreas CA, and a low IOS that , as well as a meticulous breast workup. It also emphasizes that even tiny breast cancers have a small but real risk of metastatic spread. Determination of the correct primary source in these cases may not be only an academic exercise, since the treatment and prognosis of metastatic breast cancer (especially receptor positive) and metastatic gastric cancer are different.
BREAST CANCER most commonly metastasizes to the regional nodal Having to do with nodes. See node.
NODAL - Interpreted language implemented on Norsk Data's NORD-10 computers. Used by CERN and DESY high energy physics labs to control their accelerator hardware, PADAC and SEDAC. Included trackball input, graphics. basins, lungs, bone, liver, and brain. (1) Gastrointestinal (GI) tract metastases are uncommon, occurring in 4% to 18% of patients with advanced disseminated disease. (2, 3) One series in particular has reviewed that subset of breast cancer patients with gastric metastases. (4) All patients in that series, as in other previous reports, (5-10) had a known diagnosis of breast cancer when the gastric lesion was discovered. We describe a case in which minimal breast cancer was retrospectively found to be the primary tumor during the workup of a patient who was first diagnosed with carcinoma of unknown primary and was later presumed to have metastatic gastric cancer.
A 53-year-old white woman with a history of diabetes, dyspepsia dyspepsia: see indigestion. , and previous cigarette and alcohol use, was evaluated in the hematology clinic at Oregon Health Sciences University (OHSU OHSU Oregon Health & Science University (Portland, OR, USA) ) for refractory anemia of 2 years' duration. The anemia was originally thought to be due to erythropoietin deficiency, but after 6 months of successful replacement therapy, it became refractory to this treatment. Bone marrow biopsy Bone marrow biopsy
A procedure in which cellular material is removed from the pelvis or breastbone and examined under a microscope to look for the presence of abnormal blood cells characteristic of specific forms of leukemia and lymphoma. showed metastatic signet-ring cell adenocarcinoma. Esophagogastroduodenoscopy (EGD Esophagogastroduodenoscopy (EGD)
An imaging test that involves visually examining the lining of the esophagus, stomach, and upper duodenum with a flexible fiberoptic endoscope.
Mentioned in: Bleeding Varices
esophagogastroduodenoscopy. ) revealed multiple polypoid lesions, diffusely distributed within the gastric mucosa (Fig 1). There were no dominant masses, and no thickened gastric folds of gastric cancer were seen. Biopsy showed signet-ring cell adenocarcinoma with the same histologic pattern of tumor cells seen on the bone marrow examination Bone marrow examination refers to the pathologic analysis of samples of bone marrow obtained by bone marrow biopsy (often called a trephine biopsy) and bone marrow aspiration. . An extensive staging workup was then done, including posteroanterior and lateral chest radiographs and computed tomography of the chest, abdomen, and pelvis, which were unremarkable. A diagnosis of gastric cancer with metatastases to the bone marrow was made.
The patient was presented at the OHSU GI tumor board to discuss treatment options. During that presentation, the pathologist (C.C.) noted that although the tumor was of signet-ring cell type, it had a keratin keratin (kĕr`ətĭn), any one of a class of fibrous protein molecules that serve as structural units for various living tissues. The keratins are the major protein components of hair, wool, nails, horn, hoofs, and the quills of feathers. profile consistent with an upper GI, breast, ovarian, or lung primary. On immunohistochemical staining, the cancer was found to be ER+/PR+, Her-2/neu negative, PAS mucin mucin: see glycoprotein. CK7+, GCDFP 15+, and CK 20-, TTF-, and CA-125--. These results, combined with the endoscopist's impression that the tumor had an appearance more consistent with metastatic disease than with a primary gastric cancer, led to the discussion of occult breast cancer as a possible primary lesion. Accordingly, the patient was next referred to our multidisciplinary breast clinic.
The patient's metastatic workup had included a clinical breast examination (CBE CBE Commander of the Order of the British Empire (a Brit. title)
CBE n abbr (= Companion of (the Order of) the British Empire) → título de nobleza
CBE n abbr (= ), as well as a screening mammogram. While the CBE raised the question of a mass in the upper outer quadrant of the right breast, the mammogram revealed two clustered groups of pleiomorphic calcifications in the left breast (Fig 2).
During the breast clinic consultation, the patient had no breast-related complaints. She was premenopausal pre·me·no·paus·al
Of or relating to the years or the stage of life immediately before the onset of menopause.
premenopausal adjective , gravida 7, para 1, abortus 6. Her age at menarche menarche /me·nar·che/ (me-nahr´ke) establishment or beginning of the menstrual function.menar´cheal
The first menstrual period, usually during puberty. was 13, and her menstrual cycles were reported as regular. She denied any family history of breast, ovarian, or other cancers. Review of systems was positive for night sweats and peripheral neuropathy due to longstanding diabetes mellitus.
Physical examination revealed a thin woman with normal vital signs and in no acute distress. The breast examination demonstrated symmetric, small breasts. The nipples and overlying overlying
suffocation of piglets by the sow. The piglets may be weak from illness or malnutrition, the sow may be clumsy or ill, the pen may be inadequate in size or poorly designed so that piglets cannot escape. skin were normal bilaterally. Palpation palpation /pal·pa·tion/ (pal-pa´shun) the act of feeling with the hand; the application of the fingers with light pressure to the surface of the body for the purpose of determining the condition of the parts beneath in physical diagnosis. revealed bilateral thickened fibrocystic fibrocystic /fi·bro·cys·tic/ (-sis´tik) characterized by an overgrowth of fibrous tissue and development of cystic spaces, especially in a gland.
adj. tissue in the upper outer quadrant of each breast. Careful palpation of these areas revealed no dominant or suggestive masses. There was no cervical, supraclavicular, or axillary ax·il·lar·y
Relating to the axilla.
Located in or near the armpit.
Mentioned in: Mastectomy
of or pertaining to the armpit. adenopathy on either side. Ultrasound examination of each upper outer quadrant confirmed the presence of bilateral fibrocystic tissue without any areas of suspicion.
However, a "second reading" of the mammogram reported two distinct sites of suggestive calcification in the left breast. The first area was located deep and centrally and was interpreted as BI-RADS (Breast Imaging Reporting and Data System) III; a second more superficial area was more suggestive (BI-RADS IV). Neither of these areas were palpable on CBE, and they were therefore biopsied by stereotactic stereotactic /ster·eo·tac·tic/ (-tak´tik)
1. characterized by precise positioning in space; said especially of discrete areas of the brain that control specific functions.
2. pertaining to stereotactic surgery. core biopsy. While the first area showed only benign fibrocystic tissue, the second was found to be moderately differentiated invasive cluctal carcinoma with a lobular lob·ule
1. A small lobe.
2. A section or subdivision of a lobe.
lob growth pattern and signet-ring cell features (Fig 3). The tumor was ER+/PR+, Her-2/neu negative, and the remaining histologic and immunostaining profile also matched those of both the gastric and bone marrow biopsies (Fig 3). Thus, the patient was given a diagnosis of breast cancer metastatic to the stomach and bone marrow.
Although cytotoxic chemotherapy was recommended, the patient opted for hormonal therapy and was given arimidex. She remains transfusion dependent. No treatment for the primary breast tumor was deemed necessary at this time.
Although breast cancer metastatic to the stomach is a well-known phenomenon, this case has several unusual features. First, while such lesions typically appear in patients with a well-established primary breast cancer (2-10) and up to 30 years after the diagnosis (9)), our patient's primary breast lesion was found only after the discovery of the gastric lesion, resulting in the initial consideration of the diagnosis of gastric cancer. Review of the literature reveals only two cases in which the GI metastasis was found first, and in neither of these cases was the GI lesion in the stomach. (11,12)
Indeed, the diagnosis of breast cancer could easily have been missed in this patient, since the original mammogram report was thought to be a "red herring." The correct diagnosis in this case can in part be attributed to the multidisciplinary nature of our tumor boards. In accordance with the guidelines of the Commission on Cancer, our tumor boards use a "working format" that discusses cases prospectively, as early as the workup phase, to guide diagnosis and treatment. (13)
Second, although the described breast primaries in cases with gastric metastases are typically large and clinically obvious, in our case the primary was actually occult (Fig 2). In a series of seven cases reported by Schwarz et al, (4) the primary tumor was stage I in only one case, and that lesion was palpable on CBE (R. Schwarz, MD, oral communication, June 1999). in contrast, the lesion we found was radiographically less than 5 mm (Fig 2) and was therefore clinically T1aN0, so-called minimal breast cancer. Thus, our case illustrates that a diagnosis of breast cancer metastatic to the stomach may require a high index of suspicion, as well as a standard, rigorous breast workup (beyond CBE alone), and it also emphasizes that even tiny breast cancers have a small but real risk of metastatic spread. (1)
Despite these unique features, our case also illustrates some well-described features of breast cancer metastatic to the stomach. As in other reports, our patient's gastric mucosal involvement showed a diffuse (rather than solitary) pattern (Fig 1) (2,4,11) and lobular features on histology (Fig 3). (4) The predilection for infiltrating lobular (as opposed to ductal) breast tumors to spread to unusual serosal and endocrine sites is well described but poorly understood. (4,14)
We agree with Schwarz et al (4) that because of the relative rarity of gastric cancer compared with breast cancer, the diagnosis of breast cancer metastatic to the stomach should be considered when a malignant gastric lesion suggesting a metastatic focus is found, in a female patient. The morphology of the metastatic gastric lesions on endoscopy and the immunostaining features (such as ER, PR, and GCDFP positivity (15) and the keratin pattern (16)) help to elicit the correct diagnosis. Determination of the correct primary source in these cases is not just an academic exercise, since the treatment and prognosis of metastatic breast cancer (especially receptor positive disease) and metastatic gastric cancer are different.
The treatment of widely metastatic breast cancer involves mainly cytotoxic chemotherapy or endocrine manipulation. (17) Endocrine manipulation may entail surgical or radiation-induced castration castration, removal of the sex glands of an animal, i.e., testes in the male, or ovaries and often the uterus in the female. Castration of the female animal is commonly referred to as spaying. , antiestrogens such as tamoxifen tamoxifen (təmŏk`sĭfĕn'), synthetic hormone used in the treatment of breast cancer. Introduced in 1978, tamoxifen is used to prevent recurrences of cancer in women who have already undergone surgery to remove their tumors. , progestins, aminoglutethimide and aromatase inhibitors, and luteinizing hormone--releasing hormone analogs. In most series, response rates to endocrine therapy for women with ER-positive, PR-positive tumors range from 65% to 75%. (17) Oophorectomy Oophorectomy Definition
Oophorectomy is the surgical removal of one or both ovaries. It is also called ovariectomy or ovarian ablation. If one ovary is removed, a woman may continue to menstruate and have children. is generally recommended as the first-line endocrine treatment for premenopausal women older than 35 and without significant visceral or marrow involvement, with goserelin goserelin /go·se·rel·in/ (go´se-rel?in) a synthetic gonadotropin-releasing hormone; on prolonged administration it suppresses release of gonadotropins and is used as the acetate salt to treat breast and prostate carcinomas and or tamoxifen as alternative agents. (17,18) Although this patient had an ER-positive, PR-positive tumor, endocrine therapy would not be the first choice because of its slow onset of action onset of action Pharmacology The length of time needed for a medicine to become effective. See Therapeutic drug monitoring. , the presence of visceral organ involvement, and significant hematopoietic hematopoietic /he·ma·to·poi·et·ic/ (-poi-et´ik)
1. pertaining to hematopoiesis.
2. an agent that promotes hematopoiesis.
1. pertaining to or affecting the formation of blood cells. depression.
Conventional chemotherapeutic regimens for patients with clinically disseminated breast cancer include doxorubicin-based or taxane therapy. (17,18) Although the presence of significant hematopoietic depression due to the myelophthisic sydrome produced by bone marrow infiltration with tumor may preclude the use of full-dose conventional chemotherapy, we believe that aggressive eradication of tumor from the marrow may actually improve hematopoiesis Hematopoiesis
The process by which the cellular elements of the blood are formed. The three main types of cells are the red cells (erythrocytes), which serve to carry oxygen, the white cells (leukocytes), which function in the prevention of and recovery from . Furthermore, we have found that weekly taxane therapy has shown less myelosuppression than the standard 3-week dosage regimen. (19,20) Additonally, myelostimulating factors such as G-CSF G-CSF granulocyte colony-stimulating factor.
granulocyte-colony stimulating factor.
G-CSF Granulocyte colony-stimulating factor Molecular therapeutics A biological response modifier, the recombinant DNA form of can be supplemented to augment marrow recovery after anthracycline or taxane chemotherapy. (20) Thus, we favor treatment of systemic breast cancer in this setting with doxorubicin-based or weekly scheduled taxane therapy.
In contrast to previously reported cases of breast cancer metastatic to the stomach, in which the primary lesions were previously known and often clinically obvious, we describe a case in which minimal breast cancer was found in retrospect to be the primary tumor during the workup of a patient with presumed metastatic gastric cancer. A high index of suspicion, a multidisciplinary approach to the patient's workup, attention to the morphology of the gastric lesions on endoscopy, and the immunostaining features of the tumor were all instrumental in eliciting the correct diagnosis, which in turn led to a significant change in both the treatment recommendation and expected prognosis.
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(language) ADM - A picture query language, extension of Sequel2.
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RELATED ARTICLE: KEY POINTS
* Gastric metastasis from breast cancer is uncommon.
* The vast majority of patients with gastric metastases have advanced breast cancer.
* Tumors of unknown primary site require meticulous clinical and pathologic evaluation.
From the Departments of surgery (Section of Surgical Oncology), Medicine (Divisions of Hematology/Medical Oncology and Gastroenterology), and Pathology, Oregon Health Sciences University, Portland.
Reprint requests to John T. Vetto, MD, Oregon Health Sciences University, Section of Surgical Oncology, L223A 3181 SW Sam Jackson Park Rd, Portland, OR 97201-3098.