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Requests for reprints should be addressed to Ami Schattner, MD, Department of Medicine, Hebrew University-Hadassah Medical School, Kaplan Medical Center, 76100 Jerusalem, Israel.
Department of Medicine, Laniado Hospital, Sanz Medical Centre , Netanya, IsraelFaculty of Medicine, Hebrew University and Hadassah Medical School, Jerusalem, IsraelFaculty of Medicine, Ariel University, Ariel, Israel
A healthy 28-year-old mother of 3 referred herself to the hospital because of leg pain and was admitted. Examination and Doppler ultrasound showed only varicose veins, without deep vein thrombosis or plantar fasciitis, and pallor. Hemoglobin (Hb) was 3.9 g/dL (mean corpuscular volume 60.7 fL, mean corpuscular hemoglobin 14.7 pg, red cell distribution width 18.4%), with normal white blood cells/platelets. The previous count was performed on the birth of her youngest son, 1.5 years prior showing Hb 10.8 gr/dL (mean corpuscular volume 89.4 fL). She reported normal diet and menses, had no gastrointestinal complaints and no medications or relevant family history.
Further tests showed microcytosis/anisocytosis on the blood smear, 1.9% reticulocytes (absolute count 49,970, reticulocyte production index 0.28), iron 17 μg/dL, transferrin 315 mg/dL (saturation 3.77%), ferritin 4.1 ng/mL, B12 >2000 pg/mL (N <950), folate 2.1 ng/mL. Serum lactate dehydrogenase (LDH) was consistently 821-991 IU/mL (N <225) but haptoglobin, bilirubin, and all hepatic and muscle enzymes were repeatedly normal, as were C-reactive protein (1.5 mg/dL), albumin (4.1 g/L), glucose, electrolytes, renal function tests, urinalysis, and lipids. Fecal occult blood test was negative.
She received packed cells transfusions and would have been discharged for ambulatory workup of iron deficiency anemia had not the combination of increased serum B12 and LDH suggested an underlying tumor. Computed tomography demonstrated a huge liver mass and a mass in the right colon (Figure). Colonoscopy confirmed a nonobstructing carcinoma and biopsies (both sites) demonstrated adenocarcinoma. Serum carcinoembryonic antigen was >4000 ng/mL. She was referred for oncological treatment and genetic/molecular workup.
FigureContrast-enhanced computed tomography of the chest, abdomen, and pelvis. Axial image (A) and coronal image (D) show a large solid macrolobulated mass occupying most of the right hemiliver [marked by the arrows in image (D)]. A large mass was identified in the ascending colon, narrowing the lumen with no dilation of the proximal bowel [dashed arrows in (B) and (D)]. Enlarged mesenteric lymph nodes were seen in the right lower abdomen [arrow heads in (C) and (D)]. Endoscopic biopsy of the colonic mass and ultrasound-guided biopsy of the hepatic mass diagnosed well- to moderately differentiated adenocarcinoma in both biopsies. Foci of poorly differentiated adenocarcinoma were identified in the hepatic mass.
Our patient's misfortune saddened us all, but her presentation offers some important insights.
First, we saw once more that young patients can tolerate severe degrees of anemia (in this case, ∼33% of her baseline Hb) developing gradually with no symptoms whatsoever.
Second, an entirely normal biochemistry panel (C-reactive protein, albumin, liver enzymes) cannot rule out stage IV cancer with extensive liver spread.
Third, young age at presentation and absence of risk factors are not incompatible with colorectal cancer. In fact, recent epidemiological trends of increasing diagnosis in younger people has led the US Preventive Services Task Force to recommend starting screening at age 45 years (down from 50) in populations at moderate risk. Young patients 20-39 years old have had the highest increase in incidence (57%-66% increase in the United States in 2015 ± 1 year vs 2001 ± 1 year) and are more likely to be metastatic when diagnosed.
Right-sided colonic lesions are notoriously asymptomatic, and presentation as iron-deficiency anemia is typical through occult bleeding. The single negative occult blood test must have been a sampling-dependent false negative.
Fourth, “the devil is in the details,” as the idiom goes. The patient's most unusual telltale findings were the raised LDH and B12 levels. Both are established tumor markers (in the absence of an alternative explanation), and can be seen in myriad malignancies. Serum LDH was found to be frequently increased in cancer patients (hematological, solid tumors) and associated with worse prognosis.
The mechanism is probably linked to an increased glucose uptake by rapidly proliferating cells, LDH required for its processing, and release through damaged cell membrane. The mechanism of elevated B12 in cancer is poorly understood, but while unexplained high B12 levels (defined as >1000 ng/L) can occur in other conditions, a persistent increase appears to be most strongly associated with solid cancer (hazard ratio 5.90; 95% confidence interval, 2.79-12.45; P < .001),
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