199
Breast Disease 35 (2015) 199–201 DOI 10.3233/BD-150403 IOS Press
Case report
Multiple myeloma or metastatic carcinoma breast: Diagnostic dilemma in a case presenting with lytic bony lesion Harish Chandraa,∗, Smita Chandraa and Sanjiv Kumar Vermab a
Department of Pathology, Himalayan Institute of Medical Sciences, Swami Ram Nagar, Doiwala, Uttarakhand, India b Department of Medicine, Himalayan Institute of Medical Sciences, Swami Ram Nagar, Doiwala, Uttarakhand, India
Abstract. Carcinoma breast is common tumor which tends to metastasize to different organs but diagnostic difficulty may arise if known case of carcinoma eventually presents with another secondary malignancy with clinical features which closely mimics with metastatic carcinoma. This overlapping of symptoms may lead to delayed diagnosis of secondary malignancy with worsening of the condition of patient due to lack of specific treatment. The present case is being reported where a known case of primary breast carcinoma presented with scapular erosions suggesting metastasis. However, despite treatment her worsening condition necessitated further work up revealing multiple myeloma. The case signifies the pitfall due to overlapping of symptoms and draws attention to the fact that every known case of primary carcinoma suggestive of metastasis should also be investigated in light of another secondary malignancy. Early diagnosis of secondary malignancy followed by specific treatment would be helpful in improved prognosis of the patient. Keywords: Multiple myeloma, breast carcinoma, diagnostic dilemma
1. Introduction Carcinoma breast is common tumor which tends to metastasize to different organs including lung, brain or bone with variable metastatic period ranging from months to years after primary presentation [1,2]. However, diagnostic difficulty may arise if a known case of breast carcinoma eventually presents with another secondary malignancy with clinical features which closely mimics with metastatic carcinoma. This overlapping of symptoms may lead to delayed diagnosis of secondary ∗ Corresponding author: Harish Chandra, Department of Pathology, Himalayan Institute of Medical Sciences, Swami Ram Nagar, Doiwala, Dehradun-248140, Uttarakhand, India. Tel.: +91 9411718442; E-mail: [email protected].
malignancy with further worsening of the condition of patient due to lack of specific treatment. The present case is therefore being reported where a known case of primary breast carcinoma presented with scapular erosions suggesting metastasis. However, despite treatment her worsening condition necessitated further work up which revealed multiple myeloma. The case thus signifies the pitfall due to overlapping of symptoms between metastatic breast carcinoma and multiple myeloma and draws attention to the fact that every known case of primary carcinoma suggestive of metastasis should also be investigated in light of another secondary malignancy. Early diagnosis of secondary malignancy followed by specific treatment would be helpful in improved prognosis of the patient.
c 2015 – IOS Press and the authors. All rights reserved 0888-6008/15/$35.00
200
H. Chandra et al. / Multiple myeloma or metastatic breast carcinoma
2. Case report 63 years old female was histopathologically diagnosed with infiltrating ductal carcinoma of right breast with stage T1 N0 M0 in April 1995. All the resected margins, skin, subareolar margins and level I right axillary lymph nodes were free of tumor. Immunohistochemistry for ER, PR and Her-2-neu receptors were not performed due to patient’s reluctance and financial constraints. Her hematological, biochemical and radiological investigations were within normal limits at that time. She received chemotherapy comprising six cycles every 28 days of doxorubicin (60 mg/m2 ) and paclitaxel (200 mg/m2 ) along with radiotherapy. Her follow up was uneventful except for history of developing hypothyroidism. After about 15 years she complained of pain in right shoulder along with generalized weakness. X-ray of right shoulder revealed lytic lesion with erosion of glenoid of right scapula with focal sclerosis. CT scan showed lytic lesion with partially sclerotic margin. Her bone scan showed mild to moderate increased radioactive uptake suggesting skeletal metastasis. In view of known case of breast carcinoma and radiological findings the diagnosis of metastasis to scapula was considered and the patient was subjected to radiotherapy. However, her condition worsened which necessitated further work up along with bone marrow examination for the presence of metastatic cells in marrow. Her biochemical investigations showed increased total protein (9.3 gm/dl) and decreased albumin (1.8 gm/dl). Serum calcium was increased (12.3 gm/dl) with reduced phosphorus (1 mg/dl) and mildly increased serum alkaline phosphatase. Her hematological investigations showed severe normocytic normochromic anemia (Hemoglobin 7.7 gm%). The bone marrow examination revealed increased mature and immature plasma cells (36%) and possibility of multiple myeloma was suggested. On serum electrophoresis M band was seen at gamma globulin region and the diagnosis of multiple myeloma was confirmed. She was immediately started with chemotherapy comprising of bortezomib and dexamethasone. However, she further developed shortness of breath, pedal edema, anasarca and eventually succumbed to her illness.
3. Discussion Breast carcinoma is considered to be common neoplasm showing skeletal metastasis [3]. However bony
lesions may also be produced by another malignancy and this overlapping of symptoms may prove to be diagnostic pitfall for secondary malignancy. Literature has reported several secondary malignancies like leukemia, sarcomas and lung carcinoma following post mastectomy radiotherapy even after decades of exposure [4–6]. Secondary multiple myeloma has also been rarely reported after carcinoma breast but camouflage by lytic lesions may lead to difficulty in distinguishing multiple myeloma from metastatic breast cancer [7]. This diagnostic pitfall due to overlapping of symptoms may delay the diagnosis of multiple myeloma leading to poor prognosis due to lack of specific treatment. The present case presented similarly and bone marrow examination was the first examination which suggested multiple myeloma which was later confirmed by protein electrophoresis. However, careful examination of the routine biochemical and radiological investigations may play crucial role in suspecting multiple myeloma instead of metastasis. The present case showed increased serum proteins with reversal of albumin: globulin ratio and which might be the first indication of suspecting myeloma. Another important feature is that myeloma bony lesions are considered to be osteolytic with decreased osteoblastic activity while lesions of breast metastasis have both blastic and lytic activity [8]. Myeloma bony lesions are therefore considered to have negative bone scans due to the absence of activated osteoblasts which are involved in uptake of radioactive elements [7]. However, the bone scan in the present case was suggestive of metastasis which further added to diagnostic dilemma. Kyle et al. have observed blastic lesions in 0.5% of multiple myeloma cases out of total 1027 cases studied [9]. The blastic lesions in multiple myeloma may result in increased radioactive uptake on bone scan and cases with positive bone scan in multiple myeloma have been reported which may also have implication with disease progression and prognosis [10,11]. The case also draws attention to the question of biopsy at suspected metastatic site which has also been raised by previous studies and case reports [7,12]. Hough et al. concluded that biopsy should be considered unless contraindicated so as to prevent the pitfall due to overlapping of symptoms by metastatic breast cancer and multiple myeloma [7]. The present authors also recommend either bone marrow examination or biopsy/FNAC of the metastatic site in suspected case of breast metastasis to exclude the possibility of multiple myeloma. Thus to conclude the case lays the importance of the fact that every known case of primary breast carcinoma
H. Chandra et al. / Multiple myeloma or metastatic breast carcinoma
with suspected metastasis should also be investigated in light of another secondary malignancy. Multiple myeloma should be considered as an important differential diagnosis in a case of carcinoma breast showing lytic lesion. Routine biochemical and radiological investigations may be helpful in providing an initial hint for distinguishing metastasis and multiple myeloma which may be supplemented by biopsy/FNAC of the metastatic site or bone marrow examination for definite diagnosis. Early diagnosis of multiple myeloma is important which enables prompt initiation of specific treatment and thus improving the prognosis of the patient.
References [1]
[2]
Dawood S, Lei X, Litton JK, Buchholz TA, Hortobagyi GN, Gonzalez-Angulo AM. Incidence of brain metastases as a first site of recurrence among women with triple receptor-negative breast cancer. Cancer 2012, 118:4652-9. Fuju T, Yajima R, Yamaki E, Kohsaka T, Yamaguchi S, Tsutsumi S, et al. Pulmonary metastasis from breast cancer with an 18 year disease free interval: Implication of the role of surgery. Int Surg 2012;97:281-4.
[3]
201
Qureshi A, Shams U, Akhter A, Riaz S. Metastatic bone disease as seen in ourclinical practice-experience at a tertiary care center in Pakistan. Asian Pac J Cancer Prev 2012; 13:4369-71. [4] Mery CM, George S, Bertagnolli MM, Raut CP. Secondary sarcomas after radiotherapy for breast cancer: sustained risk and poor survival. Cancer 2009;115:4055-63. [5] Zablotska LB, Neugut AL. Lung carcinoma after radiation therapy in women treated with lumpectomy or mastectomy for primary breast carcinoma. Cancer 2003;97:1404-11. [6] Chandra H, Chandra S, Verma SK, Pathak VP. An unusual case of chronic lymphocytic leukemia following breast carcinoma on chemotherapy. J Postgrad Med 2011;57:55-6 [7] Hough B, Brufsky A, Lentzsch S. Metastatic breast cancer or multiple myeloma? Camouflage by lytic lesions. J Oncol 2010; 2010:509530. [8] Roodman GD, Mechanisms of bone metastasis. N Engl J Med 2004; 350:1655-64. [9] Kyle RA, Gertz MA, Witzig TE, Lust JA, Lacy MQ, Dispenzieri A, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 2003;78: 21-33. [10] Bataille R, Chevalier J, Rossi M, et al: Bone scintigraphy in plasma-cell myeloma. Radiology 1982; 145:801-804 [11] Murthy NJ, Rao H, Friedman AS. Positive findings on bone scan in multiple myeloma. South Med J. 2000; 93: 1028-9. [12] Clayer M, Duncan W. Importance of biopsy of new bone lesions in patients with previous carcinoma. Clin Orthop Relat Res 2006;451:208-11.
Breast Disease 35 (2015) 199–201 DOI 10.3233/BD-150403 IOS Press
Case report
Multiple myeloma or metastatic carcinoma breast: Diagnostic dilemma in a case presenting with lytic bony lesion Harish Chandraa,∗, Smita Chandraa and Sanjiv Kumar Vermab a
Department of Pathology, Himalayan Institute of Medical Sciences, Swami Ram Nagar, Doiwala, Uttarakhand, India b Department of Medicine, Himalayan Institute of Medical Sciences, Swami Ram Nagar, Doiwala, Uttarakhand, India
Abstract. Carcinoma breast is common tumor which tends to metastasize to different organs but diagnostic difficulty may arise if known case of carcinoma eventually presents with another secondary malignancy with clinical features which closely mimics with metastatic carcinoma. This overlapping of symptoms may lead to delayed diagnosis of secondary malignancy with worsening of the condition of patient due to lack of specific treatment. The present case is being reported where a known case of primary breast carcinoma presented with scapular erosions suggesting metastasis. However, despite treatment her worsening condition necessitated further work up revealing multiple myeloma. The case signifies the pitfall due to overlapping of symptoms and draws attention to the fact that every known case of primary carcinoma suggestive of metastasis should also be investigated in light of another secondary malignancy. Early diagnosis of secondary malignancy followed by specific treatment would be helpful in improved prognosis of the patient. Keywords: Multiple myeloma, breast carcinoma, diagnostic dilemma
1. Introduction Carcinoma breast is common tumor which tends to metastasize to different organs including lung, brain or bone with variable metastatic period ranging from months to years after primary presentation [1,2]. However, diagnostic difficulty may arise if a known case of breast carcinoma eventually presents with another secondary malignancy with clinical features which closely mimics with metastatic carcinoma. This overlapping of symptoms may lead to delayed diagnosis of secondary ∗ Corresponding author: Harish Chandra, Department of Pathology, Himalayan Institute of Medical Sciences, Swami Ram Nagar, Doiwala, Dehradun-248140, Uttarakhand, India. Tel.: +91 9411718442; E-mail: [email protected].
malignancy with further worsening of the condition of patient due to lack of specific treatment. The present case is therefore being reported where a known case of primary breast carcinoma presented with scapular erosions suggesting metastasis. However, despite treatment her worsening condition necessitated further work up which revealed multiple myeloma. The case thus signifies the pitfall due to overlapping of symptoms between metastatic breast carcinoma and multiple myeloma and draws attention to the fact that every known case of primary carcinoma suggestive of metastasis should also be investigated in light of another secondary malignancy. Early diagnosis of secondary malignancy followed by specific treatment would be helpful in improved prognosis of the patient.
c 2015 – IOS Press and the authors. All rights reserved 0888-6008/15/$35.00
200
H. Chandra et al. / Multiple myeloma or metastatic breast carcinoma
2. Case report 63 years old female was histopathologically diagnosed with infiltrating ductal carcinoma of right breast with stage T1 N0 M0 in April 1995. All the resected margins, skin, subareolar margins and level I right axillary lymph nodes were free of tumor. Immunohistochemistry for ER, PR and Her-2-neu receptors were not performed due to patient’s reluctance and financial constraints. Her hematological, biochemical and radiological investigations were within normal limits at that time. She received chemotherapy comprising six cycles every 28 days of doxorubicin (60 mg/m2 ) and paclitaxel (200 mg/m2 ) along with radiotherapy. Her follow up was uneventful except for history of developing hypothyroidism. After about 15 years she complained of pain in right shoulder along with generalized weakness. X-ray of right shoulder revealed lytic lesion with erosion of glenoid of right scapula with focal sclerosis. CT scan showed lytic lesion with partially sclerotic margin. Her bone scan showed mild to moderate increased radioactive uptake suggesting skeletal metastasis. In view of known case of breast carcinoma and radiological findings the diagnosis of metastasis to scapula was considered and the patient was subjected to radiotherapy. However, her condition worsened which necessitated further work up along with bone marrow examination for the presence of metastatic cells in marrow. Her biochemical investigations showed increased total protein (9.3 gm/dl) and decreased albumin (1.8 gm/dl). Serum calcium was increased (12.3 gm/dl) with reduced phosphorus (1 mg/dl) and mildly increased serum alkaline phosphatase. Her hematological investigations showed severe normocytic normochromic anemia (Hemoglobin 7.7 gm%). The bone marrow examination revealed increased mature and immature plasma cells (36%) and possibility of multiple myeloma was suggested. On serum electrophoresis M band was seen at gamma globulin region and the diagnosis of multiple myeloma was confirmed. She was immediately started with chemotherapy comprising of bortezomib and dexamethasone. However, she further developed shortness of breath, pedal edema, anasarca and eventually succumbed to her illness.
3. Discussion Breast carcinoma is considered to be common neoplasm showing skeletal metastasis [3]. However bony
lesions may also be produced by another malignancy and this overlapping of symptoms may prove to be diagnostic pitfall for secondary malignancy. Literature has reported several secondary malignancies like leukemia, sarcomas and lung carcinoma following post mastectomy radiotherapy even after decades of exposure [4–6]. Secondary multiple myeloma has also been rarely reported after carcinoma breast but camouflage by lytic lesions may lead to difficulty in distinguishing multiple myeloma from metastatic breast cancer [7]. This diagnostic pitfall due to overlapping of symptoms may delay the diagnosis of multiple myeloma leading to poor prognosis due to lack of specific treatment. The present case presented similarly and bone marrow examination was the first examination which suggested multiple myeloma which was later confirmed by protein electrophoresis. However, careful examination of the routine biochemical and radiological investigations may play crucial role in suspecting multiple myeloma instead of metastasis. The present case showed increased serum proteins with reversal of albumin: globulin ratio and which might be the first indication of suspecting myeloma. Another important feature is that myeloma bony lesions are considered to be osteolytic with decreased osteoblastic activity while lesions of breast metastasis have both blastic and lytic activity [8]. Myeloma bony lesions are therefore considered to have negative bone scans due to the absence of activated osteoblasts which are involved in uptake of radioactive elements [7]. However, the bone scan in the present case was suggestive of metastasis which further added to diagnostic dilemma. Kyle et al. have observed blastic lesions in 0.5% of multiple myeloma cases out of total 1027 cases studied [9]. The blastic lesions in multiple myeloma may result in increased radioactive uptake on bone scan and cases with positive bone scan in multiple myeloma have been reported which may also have implication with disease progression and prognosis [10,11]. The case also draws attention to the question of biopsy at suspected metastatic site which has also been raised by previous studies and case reports [7,12]. Hough et al. concluded that biopsy should be considered unless contraindicated so as to prevent the pitfall due to overlapping of symptoms by metastatic breast cancer and multiple myeloma [7]. The present authors also recommend either bone marrow examination or biopsy/FNAC of the metastatic site in suspected case of breast metastasis to exclude the possibility of multiple myeloma. Thus to conclude the case lays the importance of the fact that every known case of primary breast carcinoma
H. Chandra et al. / Multiple myeloma or metastatic breast carcinoma
with suspected metastasis should also be investigated in light of another secondary malignancy. Multiple myeloma should be considered as an important differential diagnosis in a case of carcinoma breast showing lytic lesion. Routine biochemical and radiological investigations may be helpful in providing an initial hint for distinguishing metastasis and multiple myeloma which may be supplemented by biopsy/FNAC of the metastatic site or bone marrow examination for definite diagnosis. Early diagnosis of multiple myeloma is important which enables prompt initiation of specific treatment and thus improving the prognosis of the patient.
References [1]
[2]
Dawood S, Lei X, Litton JK, Buchholz TA, Hortobagyi GN, Gonzalez-Angulo AM. Incidence of brain metastases as a first site of recurrence among women with triple receptor-negative breast cancer. Cancer 2012, 118:4652-9. Fuju T, Yajima R, Yamaki E, Kohsaka T, Yamaguchi S, Tsutsumi S, et al. Pulmonary metastasis from breast cancer with an 18 year disease free interval: Implication of the role of surgery. Int Surg 2012;97:281-4.
[3]
201
Qureshi A, Shams U, Akhter A, Riaz S. Metastatic bone disease as seen in ourclinical practice-experience at a tertiary care center in Pakistan. Asian Pac J Cancer Prev 2012; 13:4369-71. [4] Mery CM, George S, Bertagnolli MM, Raut CP. Secondary sarcomas after radiotherapy for breast cancer: sustained risk and poor survival. Cancer 2009;115:4055-63. [5] Zablotska LB, Neugut AL. Lung carcinoma after radiation therapy in women treated with lumpectomy or mastectomy for primary breast carcinoma. Cancer 2003;97:1404-11. [6] Chandra H, Chandra S, Verma SK, Pathak VP. An unusual case of chronic lymphocytic leukemia following breast carcinoma on chemotherapy. J Postgrad Med 2011;57:55-6 [7] Hough B, Brufsky A, Lentzsch S. Metastatic breast cancer or multiple myeloma? Camouflage by lytic lesions. J Oncol 2010; 2010:509530. [8] Roodman GD, Mechanisms of bone metastasis. N Engl J Med 2004; 350:1655-64. [9] Kyle RA, Gertz MA, Witzig TE, Lust JA, Lacy MQ, Dispenzieri A, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 2003;78: 21-33. [10] Bataille R, Chevalier J, Rossi M, et al: Bone scintigraphy in plasma-cell myeloma. Radiology 1982; 145:801-804 [11] Murthy NJ, Rao H, Friedman AS. Positive findings on bone scan in multiple myeloma. South Med J. 2000; 93: 1028-9. [12] Clayer M, Duncan W. Importance of biopsy of new bone lesions in patients with previous carcinoma. Clin Orthop Relat Res 2006;451:208-11.
