Japanese Journal of Clinical Oncology 32:64-67 (2002)
© 2002 Foundation for Promotion of Cancer Research
Locally Advanced Mucinous Carcinoma of the Breast with Sudden Growth Acceleration: a Case Report
Departments of 1Surgery, 2Pathology, 3Psychiatry, 4Plastic Surgery and 5Radiology, Yokohama City University, School of Medicine, Yokohama, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONCASE REPORTDISCUSSIONAcknowledgmentREFERENCES |
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We report a 35-year-old woman with locally advanced mucinous carcinoma of the breast with sudden growth acceleration. A pea-sized mass developed into an ulcerated large tumor within 1 month. After the combination of chemotherapy, radiation and hyperthermia, a radical mastectomy was performed, followed by repair of the skin defect by latissimus dorsi and rectus abdominis musculocutaneous flaps. Histological examination revealed a pure mucinous carcinoma with axillary lymph node involvement. Estrogen and progesterone receptors were not detected in the tumor. Twenty-five months after treatment, there is no sign of recurrent disease. Pure mucinous carcinoma generally has a less aggressive growth pattern as defined by tumor size, adherence to the overlying skin/bottom fasciae, estrogen and progesterone receptor positive and primary lymph axillary lymph node metastases. This case showed completely opposite features to all of these typical biological features of pure mucinous carcinomas.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONAcknowledgmentREFERENCES |
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Mucinous carcinoma of the breast is one of the most common special histological types of breast carcinoma, but locally aggressive growth to form a large skin ulcer is rarely seen (1,2). It is more prevalent in older patients (3,4). The biological phenotype of mucinous carcinomas is quite favorable, as reflected in substantially less nodal involvement and a higher rate of estrogen receptor- and progesterone receptor-positive cases (5). Hence it usually has a better prognosis than does invasive ductal carcinoma (1–7). This report describes a case of extremely locally advanced mucinous carcinoma of the breast with sudden growth acceleration, which occurred in a young patient.
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CASE REPORT |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONAcknowledgmentREFERENCES |
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A 35-year-old woman was admitted to the hospital because of an ulcerated large tumor in the left breast. The patient stated that she noticed a pea-sized tumor 1 month before visiting the hospital, which grew rapidly and formed a fungated ulceration. She was upset when she visited this hospital, because of the rapid development of the tumor. Physical examination revealed a large tumor ~25 cm in diameter in the left breast, which involved almost the entire breast. It was ulcerated deeply as the pectoral muscle was clearly exposed (Fig. 1a and b). Several swollen lymph nodes, 1–3 cm in diameter, were palpated in the left axilla. There was no edema in the left arm. The right breast appeared normal. Because she was so upset and confused that she seemed to have some psychological problems, we referred her to a psychiatrist on the first day of her visit to this hospital. The report from the psychiatrist indicated that she was nervous, but psychologically healthy, without any sign of mental retardation.
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Admission laboratory data revealed anemia with a hemoglobin of 5.6 mg/dl. The levels of carninoembryonic antigen and CA15-3 were normal, but type I collagen C-telopeptide was 14.1 µg/ml, which was higher than the normal range of ~4.5 µg/ml, suggesting the presence of lytic lesion in the bone. A chest and abdominal computed tomographic (CT) scan, obtained after intravenous administration of contrast material, showed the left breast tumor fixed to the chest wall and 3–4 axillary lymph nodes (Fig. 1b) without any distant metastases in the supraclavicular lymph node, lung or liver. A radionuclide bone scan, obtained after the injection of technetium-99m-labeled methylene diphosphonate, showed uptake by the sternum, which was consistent with degenerative disease due to direct invasion or metastasis.
Microscope examination of a biopsy specimen of the tumor showed that abundant extracellar mucin was accumulated around adenocarcinoma cells (Fig. 2a).
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She was treated with preoperative chemotherapy consisting of paclitaxel (160 mg/m2) by intravenous injection and THP–adriamycin (20 mg/m2) by intra-arterial injection through the left intrathoracic artery. The treatment was repeated three times every 3–4 weeks during radiotherapy. A radiation dose of 68 Gy was given to the breast tumor in fractions of 2 Gy for 40 days. She also received 42 Gy to the supraclavicular lesion and 16 Gy to the sternum. Hyperthermia was also conducted. She tolerated the treatment regimen well with only mild liver dysfunction. Macroscopically, the tumor shrank after the combination treatment (Fig. 3a). Repeated CT scan of the chest showed a 19.8% reduction in the tumor size and no evidence of distant metastasis (Fig. 3b). A radical mastectomy was performed, followed by repair of the skin defect by latissimus dorsi and rectus abdominis musculocutaneous flaps.
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Pathological examination of the surgical specimen was performed on 21 tissue blocks of the tumor 20 cm in diameter. The tumor consisted solely of cancer cell nests with extracellular mucin production. Nuclear grading of the tumor was categorized as intermediate (grade 2) (Fig. 2b). Lymphatic and blood vessel invasion were not seen in the tumor. Immunohistochemistry revealed that this tumor was negative for c-erbB2, p53 and estrogen and progesterone receptors (data not shown). Three axillary lymph nodes were involved with tumor cells which were histologically identical with those in the breast tumor. Considering the massive lymph node involvement in the axilla before chemotherapy, the degenerative change in the sternum may have been due to the direct invasion of metastatic parasternal lymph nodes. Cancer cells were not found in the pectoral muscle where the tumor had clearly invaded before treatment (Fig. 1a and b). Necrosis and calcification were seen in a large part of the tumor, suggesting that the histopathological effect was grade 2.
Twenty-five months after treatment, the patient remains well with a hot spot in the sternum on a bone scan that was reduced to half as large as that before treatment. The level of ICTP gradually decreased to the normal level of 4.3 µg/ml 11 months after surgery.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONAcknowledgmentREFERENCES |
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Because of the unusual size of the tumor for a young patient and its sudden growth acceleration, we thought that this tumor might be cystosarcoma phyllodes before the histological result of biopsy specimen was obtained. We needed to analyze her mental status that made her ignore the tumor until the extremely advanced stage and to confirm that her statement on the history of the tumor was reliable.
The reported frequency of mucinous carcinoma of the breast is as high as 3.6% (8). This type of the tumor is subclassified into two groups: ‘pure’ mucinous carcinoma that consists solely of tumor tissue with extracellular mucin production and ‘mixed’ mucinous carcinoma that also contains infiltrating carcinoma without mucin. Although the reported tumor clearly falls into the ‘pure’ mucinous type (Fig. 2), this case is unusual not only in the sudden growth acceleration, but also in biological aspects of mucinous carcinoma. The mean age of women with pure mucinous carcinoma is greater than those with non-mucinous carcinoma, with those younger than 35 years constituting only 1% of the patients (3,4). Pure mucinous carcinoma has a less aggressive growth pattern, i.e. smaller tumor size, a lower frequency of adherence to the overlying skin/bottom fasciae and primary axillary lymph node metastases and a higher percentage of positive estrogen receptor, compared with non-mucinous carcinoma (2–8). This case showed completely opposite features to all of these typical biological aspects of pure mucinous carcinomas.
There must be some explanation for the sudden growth acceleration of this tumor that led to the extremely locally advanced stage. Biological aspects of nuclear grading and status of c-erbB 2 and p53 are not correlated with the malignant potential of this tumor. The accumulation of abundant extracellular mucin around invasive tumor cells is characteristic of mucinous carcinoma. In this tumor specimen, mucin formed nests where tumor cells were degraded or had already disappeared, i.e. a ‘muconodular pattern’. This is a phenomenon that is seen when cells produce a large amount of mucin rapidly. Although it is unknown what triggered the sudden growth of this tumor, rapid enlargement of the tumor by mucin production developed the extremely locally advanced breast tumor with deep ulcer formation.
We treated this patient by a combination of chemotherapy, radiation and hyperthermia, and finally radical mastectomy was performed. Several groups have reported that the combination of doxorubicin plus paclitaxel produces a high rate of response for advanced breast cancer, probably because doxorubicin and paclitaxel are not cross-resistant (9–11). Intra-arterial infusion chemotherapy and radiation have also been reported to be effective for locally advanced or recurrent breast cancer (12,13). Based on these reports, we chose the combination of intravenous paclitaxel and intra-arterial THP–adriamycin for this patient after receiving informed consent. Although the reduction of the tumor size was only ~20% clinically, a large part of the tumor became necrotic and tumor cells were not found in the pectoral muscle where the tumor had clearly invaded before treatment. In addition, there has been no sign of recurrent disease for 25 months after treatment. These results suggest that this combined treatment may be effective for this locally advanced mucinous breast carcinoma. The prognosis of pure mucinous type is generally favorable as long as biological aspects of pure mucinous carcinoma are conserved. We need to follow up this case further before drawing a final conclusion on the outcome.
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Acknowledgment |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONAcknowledgmentREFERENCES |
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We thank Dr Hajime Kitamura for his valuable pathological comments.
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FOOTNOTES |
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+ For reprints and all correspondence: Takashi Ishikawa, Second Department of Surgery, Yokohama City University, School of Medicine, 3–9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. E-mail: tak55@med.yokohama-ac.cu.jp
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REFERENCES |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONAcknowledgmentREFERENCES |
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Received August 6, 2001; accepted October 15, 2001.
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