In January 2015, she began to complain of left hip pain “like nerve pain” radiating down to the knee, with CT showing diffuse lytic intraosseous metastases, with no new femur lesions discernable. MRI showed no displaced pathologic fracture at the time, but repeat MRI in March 2015 demonstrated progression of diffuse metastatic disease, new moderate T2 compression fracture, severe T11 compression fracture, new cord T2 signal hyperintensity, and multilevel epidural disease from T11 to the first lumbar (L1) vertebra, involving foramina of T11–T12. Neurosurgery led to decompression of spinal cord and stabilization. A subsequent left displaced femoral neck fracture was addressed with a left total hip replacement. Histology of the femur revealed metastatic IDC (Fig. 1C).

Her course was notable for further weight loss, a right femoral neck fracture, and total hip replacement surgery in May 2015 and a surgical wound opening in July 2015 that was complicated with an emergent thoracic spine wound revision and postoperative vancomycin/cefepime. She died in September 2015, likely due to a pulmonary embolus, despite being on full-dose anticoagulation. The patient’s weight loss was a significant marker of the severity of disease. Her weight loss over time could have been affected by clinical events, medical intervention, or surgical intervention (Figure 2).


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(To view a larger version of Figure 2, click here.)

The mechanisms of muscle and fat loss in cancer are not yet well elucidated and may in fact be interrelated with the development of new metastases in advanced stages of cancers. We note, with interest, potential correlations among the growth of our patient’s metastatic tumor burden and her cachexia, by quantifying changes over time in the cross-sectional area of the following five tissue types at the third lumbar (L3) vertebral axial level: tumor metastases at the vertebral spine (TU), subcutaneous fat (SF), visceral fat (VF), abdominal muscle (AM), and paraspinal muscle (PM).

METHODS

Histology

Biopsy tissues were fixed in 10% buffered formalin, paraffin embedded, and cut into 5 µm sections on a Leica microtome. The sections were stained with Gill’s hematoxylin, bluing agent, and alcoholic eosin Y at the Herbert Irvine Comprehensive Cancer Center’s molecular shared resource at the Columbia University Medical Center (Acharyya 2012)14 (Fig. 1). Histological analysis of all biopsy samples was performed by a pathologist (Table 1A).

Radiological quantification: cross-section at L3 vertebra

TU (Figure 3A), AM (Figure 3B), and PM (Figure 3C) cross-sectional areas were quantified within axial images of serial CT abdomen/pelvis scans at a superior and an inferior L3 vertebral level. The total area quantification in millimeter squared was made at both sub levels with automated tissue segmentation software based on differential Hounsfield units across user-created contours, designed by Zhao et al at the Columbia University’s Computational Imaging Analysis Laboratory. These two numbers were averaged for an average cross-sectional area across the L3 vertebral level.

To view Figure 3, click here.