Metastatic breast carcinoma mimicking multiple myeloma
Abstract: 6%-10% breast carcinomas spread to distant sites at the time of first
diagnosis. Bone is the most common site for distant metastasis from breast cancer.
Presence of bone metastasis affects patient's prognosis and the planning of treatment. We
report a case of 32 year old female who presented with a subtrochanteric fracture left
femur and multiple lytic lesions throughout the axial skeleton leading to clinical suspicion
of multiple myeloma. Incidentally on examination a breast mass was noted. This report
addresses the pitfalls of overlapping symptoms with multiple lytic lesions and potential
role of a bone marrow examination in arriving at a diagnosis of metastatic breast
carcinoma.
Keywords: Metastatic breast carcinoma, Multiple lytic lesions, Bone marrow
examination.
Introduction: Breast cancer is the most common cancer in women in many countries,
including developing countries like India. Breast cancer is increasing both in young (11per
cent per decade) and old women (16per cent per decade) There are an estimated 1,00,000 1,25,000 new breast cancer cases in India every year. Since 1990 the incidence rate has
increased 1.5% annually. Approximately 4–6% of breast cancers are metastatic at
diagnosis. Bone is the most common site of distant metastasis, and metastasis to bone are
diagnosed in 30%–85% of patients with advanced breast cancer. Bone metastasis causes
much of the morbidity and disability in patients with breast cancer.
Case report: A 32 year old female presented to our hospital with difficulty on walking
and pain in both hip regions left more than right. On physical examination she had limited
and painful movements of left hip joint. An initial X-ray of the pelvis showed a
subtrochanteric fracture of left femur along with multiple lytic lesions in the pelvis. X ray
of spine and skull also showed multiple lytic lesions. MRI of pelvis and whole spine was
done which also revealed multiple lytic lesion involving spine and pelvis, the differential
diagnosis offered was 1.multiple myeloma 2.metastasis. On general examination
incidentally a right breast mass of 1.2cms diameter was noted in upper outer quadrant, firm
in consistency with restricted mobility. A single right axillary lympnode was also palpable
in the right axilla. Ultrasound of breast showed right breast mass measuring 1.6*1.9 cms
with internal vasularity and axillary lymphnode measuring 1.5*1.2 cms.
Fine needle aspiration of the right breast mass was done and the diagnosis offered
was proliferative breast diasease and FNAC from right axillary lymphnode showed
features consistent with reactive changes. In view of clinical suspicion of multiple
myeloma a complete hemogram was done which showed a Hb 7.5g/dl, WBC
11,000/cumm and platelet count 4lakhs/cumm. No abnormal cells were seen and there was
no rouleaux, impression given was Normocytic hypochromic anemia. Biochemical profile
included, urine for Bence jones proteins which was negative, serum calcium was within
normal limits 8.4mg/dl. Serum urea nitrogen was elevated 60mg/dl, serum creatinine
2.2mg/dl. Serum protein electrophoresis was done and there was no M spike. As there was
high suspicion of multiple myeloma we went ahead with a bone marrow aspiration.
The aspiration yielded only scanty material as the needle entered a lytic area and
the smears showed only few clusters of large round to oval cells with scant cytoplasm
round to oval nucleus with coarse chromatin and one or two prominent nuclei, the cell
block was prepared with the aspirate which also showed these pleomorphic cell clusters in
a hemorrhagic background, no marrow elements were
identified. Based on the
morphology possibility of metastatic deposits of carcinoma was given. Bone marrow
biopsy was also attempted subsequently but was unsuccessful. IHC was done on the cell
block, these pleomorphic cells were positive for Pan CK. As there was a breast mass and
high degree of suspicion of metastatic carcinoma a trucut biopsy of right breast mass was
adviced. Serum CA 15.3 levels was done which is a marker of metastatic breast carcinoma.
CA 15.3 levels were highly elevated 1806U/ml(normal upto 32U/ml) which was highly
suggestive of metastatic breast carcinoma. Histopathology of trucut biopsy showed
pleomorphic ductal epithelial cells with hyperchromatic nuclei. IHC for P63 was negative,
a diagnosis of invasive duct cell carcinoma was given. Patient was referred to regional
cancer institute and presently receiving chemotherapy and is being followed up.
Discussion: 4-6% of breast carcinomas present with metastases at the time of initial
diagnosis. Bone is the most common site for metastases from breast carcinoma. Normal
interactions between the mammary gland and the bone/bone marrow-derived cells are
diverted to serve the mammary malignant process at its inception and subsequently during
the metastatic process. It is now formally a possibility that the bone marrow has the
potential to serve as a ‘sanctuary’ to protect metastatic breast cancer cells.
This protective environment may support the metastatic foci before they progress
locally to form bony metastases or equally serve as a platform from which breast cancer
cells can be stimulated locally or systemically to seed other organs or even re-seed the site
of the original primary tumor1.
Bone metastases from breast carcinoma usually presents with both blastic and lytic
lesions, blastic being more common than lytic. However it can also present with purely
lytic lesions simulating the picture of multiple myeloma. Identification of the etiology of
lytic lesions may be further difficult if the breast mass is not the initial complaint at the
time of presentation as it was in our case. Workup for a lytic lesions should first exclude
the possibility of a multiple myeloma. M spike on serum protein electrophoresis and other
biochemical parameters are useful tools to safely exclude the possibility of a multiple
myeloma but one should always remember that nonsecretory myeloma do not show a M
spike.
A bone marrow aspiration can be of great help in arriving at a diagnosis in such
cases. When in doubt Serum CA 15.3 levels can be a useful marker in metastatic breast
carcinoma2. Values more than 30u/ml are indicator of metastasis and poor prognosis.
Numerous studies have indicated that CA15.3 is a reliable marker in breast carcinoma and
correlates well with the disease stage3. A similar case was reported in literature by Daniela
Katz et al4. In our case serum CA 15.3 concentration of 1806u/ml correlated with the
diagnosis given on bone marrow aspiration and helped us to locate the primary. A bone
marrow examination helped to identify metastases which would otherwise go undetected
and unnecessary invasive surgery would be carried out which is not indicated in stage IV
breast carcinoma.
Conclusion: Taken together, this case emphasizes that it is essential to thoroughly
analyze the cause of multiple lytic lesions in each patient. In order to provide an optimal
treatment for metastatic disease, bone marrow examination should be considered unless
absolutely contraindicated and a careful differential diagnosis should be generated.
Figure 1: Multiple lytic lesion in
skull Lateral view
Figure 3 Bone marrow aspiration
showing clusters of pleomorphic
cells with scant amount of
cytoplasm coarse chromatin and
prominent nucleoli
Figure 2 Lytic lesions in pelvis
and left supratrochanteric
fracture AP view
Figure 4: Cell block showing these
pleomorphic cell clusters
Figure 5: Tru cut biopsy breast
showing pleomorphic cells with
hyperchromatic nuclei
Figure 6: IHC P63 negative
References
1
Larry J Suva, Robert J Griffin, Issam Makhoul Mechanisms of bone metastases
of breast cancer Endocrine-Related Cancer 2009 :16 :703–713.
18. O’Hanlon DM, Kerin MJ, Kent P et al. An evaluation of preoperative CA 15-3
measurement in primary breast carcinoma. Br J Cancer 1995; 71(6): 1288–1291.
2
3
S. Chourin, D. Georgescu, C. Gray, C. Guillemet,et al .Value of CA 15-3 determinationin
the initial management of breast cancer patients. Annals of Oncology 2009 : 20(5)962-964.
4
Daniela Katz MD, Dvora Aharoni MD New England Journal of Medicine 2004:27:351