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A 40-year-old Chinese man with a history of hepatitis B, cirrhosis, and hepatocellular carcinoma (HCC), status post transcatheter arterial chemoembolization and orthotopic liver transplantation in 2007, presented to the oncology and dermatology clinics with three months of worsening mid-back pain and two enlarging facial nodules. Physical examination revealed two 1-cm firm pinkto-erythematous nodules without overlying scale or crust (Fig. 1). The lesions were non-tender to palpation. The remainder of the exam revealed a 1-cm firm nodule in the left axilla. A repeat check of his alpha-fetoprotein (AFP) level was 13,298 ng/ml, increased from 7752 ng/ml several months earlier. Follow-up computed tomography imaging showed a recurrent tumor in the 5th segment of the liver with metastases to the ribs, spine, and lung, confirmed by biopsy.Punch biopsy of the facial nodules revealed nodular aggregates of atypical epithelial cells in the dermis associated with an increased number of blood vessels (Fig. 2a). The cells contained enlarged, pleomorphic, hyperchromatic nuclei, some with large basophilic nucleoli and abundant amphophilic to pale-staining cytoplasm (Fig. 2b). There were several multinucleated cells as well as typical and atypical mitotic figures and individual cell necrosis, consistent with metastatic non-small cell carcinoma. Immunoperoxidase studies revealed only focal reactivity of the tumor cells for cytokeratins AE1 and AE3 and no reactivity with melan-A. The cells were also focally reactive for CAM 5.2, and ductal structures and canaliculi were reactive for epithelial antigen membrane (EMA), CD10 and, to a lesser degree, carcinoembryogenic antigen (CEA; Fig. 2c and d).Additionally, the cells were reactive for hepatocyte paraffin 1 antigen (Hep Par 1) and AFP, confirming the diagnosis of metastatic HCC. Radiation of the facial lesions was recommended. DiscussionHCC, a rare cause of cutaneous metastasis, continues to rise in incidence and is the third leading cause of cancer mortality worldwide. 1,2 Overall, HCC has a high rate of extrahepatic metastasis (30-80% evidence of metastasis at autopsy); however, most metastatic lesions occur in the lungs (51.6%), followed by the regional lymph nodes (14-26%), adrenal glands (8.4%) and bones (5.8%). 2 There have been only 45 cases of cutaneous metastasis from HCC described in the literature since 1964.

Introduction: Quantifying cellularity is an integral component of bone marrow examinations. Estimates of marrow cellularity may influence the diagnostic interpretation of bone marrow samples. The accuracy of cellularity estimates may be influenced by the variable distribution of cellular elements within the marrow space. To better understand the degree of heterogeneity of bone marrow cellularity, we undertook a study to quantify the variable distribution of bone marrow cells in bone marrow core biopsies. Method: 8 gauge bone marrow core biopsies of 20 patients were retrospectively reviewed by 2 hematopathologists (SI,CL). The specimens were recovered from the posterior superior iliac crest using standard technique with 8G Snarecoil biopsy needles by 3 operators (KH, PK, GD). The percent cellularity was determined in sequential 0.2 X 0.4 cm portions of the core biopsies by each of the hematopathologists. Cellularities were recorded in 10% increments. Results: The mean age of the patients was 73.2 ± 1.8 years. There were 12 males and 8 females. 5 patients had monoclonal gammopathies. Anemia, multiple myeloma and thrombocytopenia were each diagnosed in three patients. 2 patients demonstrated myelodysplasia and 1 patient each had acute leukemia, leukocytosis, non-Hodgkin’s lymphoma and thrombocytosis. The mean white blood cell count, hemoglobin and platelet count were 8.7 (range 3.8–42.8), 12.2 (range 10.1–15.3), and 233 (range 91–226), respectively. The mean length of the core biopsies was 1.78 ± 0.09 cm (range 1.4–3.3) and the median number of 0.2 × 0.4 cm portions examined per core biopsy was 8 (range 5–12). In total, 165 portions were examined by each hematopathologist independently. The cellularity of 12 and 11 portions could not be determined by each of the hematopathologists, respectively, as a result of biopsy artifacts. No core biopsy showed a consistent cellularity within the examined portions, each core demonstrating a range of cellularities. Only 2/20 and 1/20 of the core biopsies, as examined by each hematopathologist, respectively, demonstrated 2 consistent cellularities. A median of 4 different cellularities were identified in each core. The mean range of cellularities of each core’s portions was 43 ± 4.6 %, and 46.5 ± 4.9 %, as determined by the 2 hematopathologists, respectively, which was statistically equivalent (paired t-test p=0.349). Conclusions: Bone marrow cellularity is heterogeneous. Cellularities of different portions of core biopsies vary significantly. Average differences between minimal and maximal portional cellularities may be as high as 46%. The accuracy of bone marrow cellularity measurements is related to the size of the biopsy specimen.

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