A 61-year-old male patient presented to the outpatient clinic in 2005 with complaints of paresthesia in his hands. Abdominal imaging studies, which he underwent previously, detected focal liver lesions. In 1996, an abdominal ultrasound carried out for epigastric pain, revealed two focal hepatic lesions presumed to be hemangiomas. This was verified by a red blood cell (RBC) scan. In 2000, an abdominal computed tomography (CT) study showed ten hepatic lesions of different sizes, however, no further investigation was performed. In 2003, the patient had an inferior wall myocardial infarction. His blood count showed a hemoglobin level of 132 g/L, white blood cell count of 6.7 × 109/L and a platelet count of 188 × 109/L. In 2005, a routine blood count showed hemoglobin of 111 g/L. A repeat ultrasound (US) detected multiple hepatic lesions, and an abdominal CT scan showed that the hepatic lesions had grown since the previous (2000) study. Another RBC scan again showed only two hemangiomas. Finally, a positron emission CT (PET-CT) scan showed uptake of fluorodeoxyglucose (FDG) in several hepatic lesions (Figure ), and a decision was made to biopsy one of the lesions. On histopathological examination, the cells of the lesion were different from the known primary and metastatic tumors of the liver, and all the immunohistochemical stains performed were negative. A neuroendocrine tumor was considered the most likely morphological diagnosis, despite negative staining for the neuroendocrine antigens, synaptophysin and chromogranin A (Figure ).
Axial fused PET-CT scans of the upper abdomen before (Right-2005) and after (Left-2009) treatment. Right- An FDG-avid lesion is seen in the left lobe of the liver (arrow). Left-The lesion is smaller with decreased intensity of FDG uptake (arrow).
Figure 2 Histological findings. A, B: Liver core needle biopsy; C, D: Bone marrow biopsy. A: Infiltration by small to medium-sized tumor cells is seen. In the left lower part of the picture, normal residual liver parenchyma is seen (HE, × 200); B: Immunohistochemical (more ...)
The patient was referred to our clinic for further evaluation. He denied any weight loss, diarrhea or flushing. On physical examination he appeared well. No lymphadenopathy was noted, his abdomen was not tender, and no signs of an enlarged liver or spleen were found. His laboratory results showed pancytopenia with a hemoglobin level of 110 g/L, white blood cells of 3.5 × 109/L, and a platelet count of 120 × 109/L. All liver function tests were normal, albumin level was 40 g/L. Blood levels of adreno-cortico-trophic hormone (ACTH) and beta-human chorionic gonadotropin (hCG) were normal, urine levels of vanilmandelic acid (VMA) and 5-hydroxyindoleacetic acid (5HIAA) were also in the normal range. An octreotide scan showed increased uptake in the liver. A bone marrow biopsy was performed, which was compatible with hairy cell leukemia with positive stains for CD-20 and Tartaric Acid Resistant Acid Phosphatase (TRAcP) (Figure and D). A repeat examination of the hepatic specimen showed positive staining for CD-20 and TRAcP (Figure ).
The patient was started on cladribine (2-chlorodeoxyadenosine-2CDA) with a diagnosis of hairy cell leukemia with hepatic involvement. No side effects were noted. Three months after treatment, a gradual rise in his blood count was seen. A follow-up CT scan showed that the hepatic lesions had not changed in size. His paresthesia had resolved.
Two years after treatment with 2CDA his blood counts had increased, his hemoglobin level was 148 g/L, white blood cell count was 6.2 × 109/L, and platelet count was 189 × 109/L. Repeat CT and an abdominal magnetic resonance imaging (MRI) scan showed that the lesions were similar in size to those shown on the previous CT. A repeat PET-CT scan about three years after treatment demonstrated that only one lesion in his left hepatic lobe still showed uptake of FDG, no uptake was observed in the other lesions (Figure ).
PET-CT and pathological findings
PET-CT scan with F18-FDG: The first PET-CT scan of 2005 (Figure ), shows multiple hypodense lesions of different sizes in the liver; some of the lesions show increased uptake of F18-FDG. The post-treatment PET-CT scan of 2009 (Figure ), shows significant improvement. All the previously hypermetabolic lesions are smaller, and all foci of increased uptake, with the exception of one, disappeared. This latter lesion, although reduced in size, still shows increased F18-FDG uptake but with lower intensity. These dynamic changes are consistent with involvement of the underlying disease. According to CT from the PET-CT scan of 2009, the lesions which did not show increased F18-FDG uptake either in 2005 or in 2009 did not change in size. This suggests that they are of a different nature i.e. hemangioma. This was proven by a labeled red blood cell nuclide scan.
Pathological findings: The submitted liver core needle biopsy was fixed in formalin (neutral 10%, pH 7.4) and embedded in paraffin wax. Sections 4 microns thick were cut and stained with hematoxylin and eosin (HE). The histological sections showed liver tissue infiltrated by diffuse aggregates of small/medium-sized uniform tumor cells, with bland oval nuclei, clear cytoplasm with no well defined cytoplasmic borders. No cellular atypia or mitotic figures were demonstrated (Figure ). For immunophenotyping, we used the standard avidin-biotin method on the paraffin sections. The slides were immunostained in the automated system ES Ventana (Ventana Medical Systems, Inc). Immunohistochemical staining showed that the cells were positive for vimentin (V9, ZYMED Laboratories, South San Francisco, CA, USA) and negative for α-smooth muscle actin/SMA (1A4, DAKO, Glostrup, Denmark), desmin (ZC 18, ZYMED Laboratories) (muscle origin), S-100 (S-100, DAKO, Glostrup, Denmark), chromogranin (Chromogranin A, DAKO, Glostrup, Denmark), synaptophysin (Synaptophysin, Z66, ZYMED Laboratories) and CD56 (T199, DAKO, Glostrup, Denmark) (neuroendocrine origin), MNF116 (MNF116, DAKO, Glostrup, Denmark), CAM 5.2 (Zym 5.2, ZYMED Laboratories), CK7 (OTVL, BioGenex, San Ramon, CA, USA), CK20 (IT-Ks20.8, BioGenex, San Ramon, CA, USA), CEA (ZC23, ZYMED Laboratories) (epithelial origin), CD31 (JC70A, DAKO, Glostrup, Denmark), CD34 (QBEnd/10, CellMarque, Rocklin, CA, USA), (vascular origin), and α-fetoprotein (α-1 DAKO, Glostrup, Denmark), and HEPA (OCH1ES, DAKO, Glostrup, Denmark), (liver origin). The Ki67 proliferation antigen was positive in about 10% of cells. Despite the fact that the tumor cells were negative for almost all the basic non-hematological immunostains, it was decided that the morphological differential diagnosis was either a neuroendocrine tumor or a glomus tumor. One month later a bone marrow trephine biopsy was performed. The bone marrow was infiltrated by sheets of tumor cells with morphological features of hairy cell leukemia (Figure ). The immunohistochemical stains for CD20 (L26 DAKO, Glostrup, Denmark), and TRAcP (ZY-9C5, ZYMED Laboratories), were positive and confirmed the diagnosis of hairy cell leukemia (Figure ). In a revision of the liver biopsy, it became clear that the tumor cells were morphologically similar to the hairy cells in the bone marrow. The immunohistochemical stains for CD20 and TRAcP were also positive and confirmed the diagnosis of hairy cell leukemia of the liver presenting as a tumoral mass (Figure ).