PMC4559873_01
Gross examination and histologic finding of the cutaneous melanoma. The pigmented skin is located on the lower right leg (black arrow) (a). The resected specimen contained granular, brown, cytoplasmic pigmented cells (white arrow) (hematoxylin-eosin stain, x400) (b)
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Fig1
In August 2008, a 44-year-old female had undergone surgery for resection of a malignant melanoma in the right lower leg and a right inguinal metastatic lymph node (Fig. 1), followed by chemotherapy with doxorubicin, adriamycin, vincristine, and interferon beta (DAV-feron).
Sequential images of abdominal computed tomography (CT). These images are from September 2012 (a), November 2012 (b), and December 2012 (c). There is a metastatic tumor in the right lobe of the liver (a). Initially, the hepatic metastases considerably respond to vemurafenib treatment, and they become almost invisible (b). Later, they grow rapidly and rupture, resulting in a large amount of free fluid within the peritoneal cavity surrounding the liver (c). The yellow arrow demonstrates the same tumor in each image
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Fig2
A retrospective and sequential analysis of the CT images suggested that a part of the liver metastases had enlarged rapidly and then ruptured with intratumoral hemorrhage during vemurafenib treatment (Fig. 2).
Cross-sectional and histologic findings of the liver at autopsy. The ruptured region (white asterisk) and subcapsular hematoma surrounding the liver (white arrow) (a). The metastatic tumor is well demarcated by a fibrous capsule (yellow arrow) (hematoxylin-eosin stain, x40) (b)
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Fig3
The background liver was completely normal, whereas exposed necrotic tissue and intratumoral hemorrhage were observed at the site of tumor rupture (Fig. 3).
Microscopic findings of the skin, liver, and lymph node specimen. The skin lesion and the liver and lymph node metastases are stained to detect Melan-A, Ki-67, phosphorylated extracellular signal regulated kinase, and phosphorylated Akt (x400)
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Fig4
Finally, for improved understanding of the mechanism of refractory metastasis, we conducted an immunohistochemical analysis of the signal transduction molecules, phosphorylated extracellular signal-regulated kinase (p-ERK), and phosphorylated Akt (p-Akt), as well as the melanocyte marker Melan-A and Ki-67 in tumor cells of the primary malignant melanoma obtained from the right lower leg and in hepatic and lymph node metastases obtained on autopsy (Fig. 4).