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case_images: Pathological features of renal medullary carcinoma. Pathologic surgical specimen of left kidney, revealing highly atypical cells arranged in nests and sheets, with intratumoral neutrophilic infiltration and peritumoral inflammation and fibrosis.
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case_images: Computed tomography (CT) of the abdomen and pelvis revealed a poorly defined mass at the midpole of the left kidney, 4.8 x 4.4 cm in size, with minimal hydronephrosis (Fig. 1). The surgical specimen contained highly atypical cells arranged in nests, sheets, and adenoid cystic patterns, with intratumoral neutrophilic infiltration and peritumoral inflammation and fibrosis (Fig. 1).
case_images: Sequential CT scans showing response to therapy. Metastatic Renal Medullary Carcinoma with Complete Remission of Disease post chemotherapy and it remained the same while on maintenance: CT scan prior to the initiation of chemotherapy revealed significant lymphadenopathy consistent with metastatic disease in the mediastinum (A), gastrohepatic ligament (B), and in the right lung (C). After Cycle 4 of chemotherapy, CT imaging revealed complete remission of mediastinal (D), gastrohepatic ligament (E), and pulmonary (F) nodules.
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case_images: CT of the chest, abdomen, and pelvis revealed mediastinal, hilar, and gastrohepatic ligament lymphadenopathy with right pulmonary nodules suspicious for metastatic disease (Fig. 2). CT of chest and abdomen after cycle 2 of PCG revealed marked decrease mediastinal, hilar, and gastrohepatic ligament lymphadenopathy with complete resolution (CR) of lung nodules and lymph nodes post completion of cycle 4 of PCG chemotherapy (Fig. 2).
case_images: Immunohistochemical Identification of Molecular Targets for Therapy. (A) Negative expression of RRM1 (defined as less than 2+/50%) was detected in the patient sample (1+/90%). (B) Negative expression of PTEN (defined as <=1+/50%) was detected in the patient sample (1+/5%, a near complete loss of expression).
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case_images: Tumor immunohistochemistry revealed below threshold expression of Ribonucleotide Reductase M1 (RRM1) expression (Figs. 3A), near complete loss of phosphatase and tensin homolog (PTEN) expression(Fig3 B) and 50% c-MET expression (positive but CISH was negative for cMET amplification); as shown in Figure 4B, loss of PTEN gene function removes the negative feedback mechanism exerted on PI3- kinanse, thereby increasing downstream signaling and increased un-inhibited cell growth.
case_images: Outline of the role of PI3K, phosphoinositide 3-kinase; PTEN, phosphatase and tensin homolog; mTOR, mammalian target of rapamycin. (A) Exhibits role of tumor suppressor gene PTEN in regulating PI3K mediated cell cycle signaling. (B) Demonstrates role of loss of PTEN inhibition in tumor genesis. (C) Highlights potential targets of cell cycle inhibitor, including Everolimus which was used in our patient.
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case_images: Tumor immunohistochemistry revealed below threshold expression of Ribonucleotide Reductase M1 (RRM1) expression (Figs. 3A), near complete loss of phosphatase and tensin homolog (PTEN) expression(Fig3 B) and 50% c-MET expression (positive but CISH was negative for cMET amplification); as shown in Figure 4B, loss of PTEN gene function removes the negative feedback mechanism exerted on PI3- kinanse, thereby increasing downstream signaling and increased un-inhibited cell growth. Figure 4C demonstrates potential targets for therapy in patients with PTEN gene loss of function, including an MTOR inhibitor.