PMC6081566_01
Axial head CT images on bone window. (a) The skull was intact on June 30, 2011. (b) Many osteolytic lesions were detected on September 13, 2017.
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The brain turned out to be intact but, unexpectedly, multiple osteolytic lesions were detected in the skull, extraordinarily obvious upon comparison with previous films taken six years earlier for other reasons (Figure 1).
Chest and abdomen CT images on bone window, September 14, 2017. Multiple osteosclerotic and osteolytic lesions involved the sternum, vertebra, sacrum, and bilateral iliac bones.
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Afterwards, a CT scan of chest and abdomen revealed osteosclerotic and osteolytic lesions similar to that of skull involving almost the whole skeleton (Figure 2) but not a single clear-cut primary tumor site could be located.
Adenocarcinoma nests in bone marrow aspiration smears (Wright-Giemsa stain, 1000x).
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The aspiration smear demonstrated very scanty hematopoietic precursors scattered among crowded groups of oval neoplastic cells with large hyperchromatic nuclei, coarse chromatin, modest granular cytoplasm, and occasionally small nucleoli (Figure 3).
Metastatic adenocarcinoma in bone marrow (Hematoxylin and eosin stain, (a) 100x; (b) 400x).
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Pathologic study of the biopsy specimen after decalcification displayed a picture of metastatic adenocarcinoma composed of round to oval tumor cells arranged in ovoid clusters, small rounded nests, cribriform nests, and focal microacinar pattern stuffed in bone marrow cavity (Figure 4).
Immunohistochemical stain of adenocarcinoma in bone marrow. (a) CK7, (b) CK8, (c) ER, and (d) PR. All were positive.
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The immunohistochemical stains gave positive results for cytokeratin 7 (CK7), cytokeratin 8 (CK8), estrogen receptor (ER) (strong, 99%), progesterone receptor (PR) (strong, 99%) (Figure 5), Smad4 (DPC4), GATA binding protein 3 (GATA-3), gross cystic disease fluid protein 15 (GCDFP-15), and mammaglobin (Figure 6).
Immunohistochemical stain of adenocarcinoma in bone marrow. Positive for (a) GATA-3, (b) GCDFP-15 (patchy staining pattern), and (c) mammaglobin (scattered staining pattern). Negative for (d) HER2.
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The immunohistochemical stains gave positive results for cytokeratin 7 (CK7), cytokeratin 8 (CK8), estrogen receptor (ER) (strong, 99%), progesterone receptor (PR) (strong, 99%) (Figure 5), Smad4 (DPC4), GATA binding protein 3 (GATA-3), gross cystic disease fluid protein 15 (GCDFP-15), and mammaglobin (Figure 6).
Mammography. (a and c) No suspicious lesions were detectable on June 25, 2012. (b and d) An about 7 to 8 mm focal asymmetry (solid arrows) at the posterior inner hemisphere of right breast and several enlarged lymph nodes at right axillary region (dashed arrow), diameter up to 12 mm, were noted on September 14, 2017.
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Mammogram brought to light a suspect primary site in the right breast as compared with films taken five years earlier for cancer screening (Figure 7).
3D maximum intensity projection (MIP) contrast subtraction study MRI of breast on September 15, 2017. There was an about 7 mm focal asymmetry at the posterior inner hemisphere of right breast (arrow).
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The lesion was also detectable in magnetic resonance imaging (MRI) (Figure 8).
Change of serum CA 15-3 (blue diamond) and alkaline phosphatase (orange square) levels (iu/ml) along the clinical course. Green arrow: tamoxifen commencement date (September 21, 2017).
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After a period of probable "tamoxifen flare" with elevation of serum CA 15-3 and alkaline phosphatase levels for six weeks, both of them dropped gradually within four months (Figure 9).
PET/CT scans. (a) Profuse bone marrow uptake (SUVmax: liver 3.1, skeleton 4.2) 15 days after starting treatment with tamoxifen, October 16, 2017. (b) Obvious resolution of previous bone marrow uptake with some residual activity in the lumbar spine (SUVmax: liver 3.3, skeleton 3.2) while on continuous tamoxifen treatment, March 5, 2018.
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The mild activity remained in the lumbar spine could be either residual metastasis or, more favored by us, compensatory hyperactive hematopoiesis in its recovery phase (Figure 10).