Composite hemangioendothelioma and its classification as a low-grade malignancy.

Hemangioendotheliomas are vascular neoplasms occupying a spectrum of biological potential ranging from benign to low-grade malignancy. Composite hemangioendothelioma (CH) is one of the less commonly encountered variants exhibiting a mixture of elements of other hemangioendothelioma subtypes, such as epithelioid, retiform, and spindle cell. Some authors have identified areas histopathologically equivalent to angiosarcoma within CH, raising the question of the true nature of this neoplasm. Although CH recurs locally, there are only 3 reported cases which metastasized. To date, 26 cases (including the present case) have been described in the literature. Herein, we describe a unique case of CH arising in the background of previous radiation therapy and long-standing lymphedema (classically associated with the development of angiosarcoma-Stewart-Treves syndrome) that harbored higher grade areas but behaved as a low-grade malignant neoplasm. This, in conjunction with the many reported cases of CH-harboring angiosarcoma-like areas, and the occasional association with a history of lymphedema, raises the question of whether this variant of hemangioendothelioma may actually be an angiosarcoma that behaves prognostically better than the conventional type. After careful study of the natural disease progression of the current case and review of the literature, we discuss justification for the continued classification of CH as a low-grade malignancy.

KRAS Testing: A Tool for the Implementation of Personalized Medicine.

Activating point mutations in codons 12, 13, and 61 of the KRAS proto-oncogene are common in colorectal, non-small cell lung, pancreatic, and thyroid cancers. Constitutively activated KRAS mutations are strongly associated with a resistance to anti-epidermal growth factor receptor (EGFR) therapies, such as panitumumab and cetuximab used for treating metastatic colorectal carcinoma and EGFR tyrosine inhibitors used for advanced non-small cell lung cancers. Since anti-EGFR therapies are costly and may exert deleterious effects on individuals without activating mutations, KRAS mutation testing is recommended prior to the initiation of anti-EGFR therapy for these malignancies. The goal of this review is to summarize the KRAS mutation testing methods. Testing is now routinely requested in the clinical practice to provide data to assign the most appropriate anticancer chemotherapy for each given patient. Review of the most relevant literature was performed. Several areas were considered: ordering of the test, selection of the sample to be tested, and review of the testing methodologies. We found that several different methods are used for clinical KRAS mutation testing. Each of the methodologies is described, and information is provided about their performance, cost, turnaround times, detection limits, sensitivities, and specificities. We also provided "tips" for the appropriate selection and preparation of the sample to be tested. This is an important aspect of KRAS testing for clinical use, as the results of the test will affect clinical decisions with consequences for the patient.

The histogenic origin of melanoma arising in respiratory epithelium of a teratomatous germ cell tumor of the mediastinum: an enigma unraveled from an unlikely source.

Mixed germ cell tumors are rare neoplasms that are known to occur in the anterior mediastinum. Characterized by two or more types of germ cell components, these tumors comprise upwards of 25% of mediastinal germ cell tumors. Even rarer are those harboring somatic-type malignancies such as carcinoma, sarcoma, and hematopoietic malignancies. To date, however, there are no known cases of melanoma arising in a malignant mixed germ cell tumor of the anterior mediastinum. We describe the first case of malignant melanoma with spindle and epithelioid components arising from respiratory epithelium in a mediastinal malignant mixed germ cell tumor of a 32-year-old male. In addition, we also provide evidence supporting the theory of neuroendocrine cells as the origin of melanoma arising in the respiratory epithelium. This case emphasizes the need to carefully evaluate all germ cell tumors, not only for a myriad of benign embryological components, but also for malignancies arising in these components, as they might change the prognosis and patient's course of treatment. This microscopic approach should bring to light the diversity of mixed germ cell tumors in addition to somatic malignancies with corresponding biologic potentials.

Rhabdomyomatous differentiation in Wilms tumor pulmonary metastases: a case report and literature review.

While sparsely reported in the literature, Wilms tumor may differentiate into more mature mesenchymal tissue types, such as skeletal muscle, following chemotherapy. The frequency of this event is unknown. Chemotherapy and radiation may induce cytodifferentiation of Wilms tumor cells or select for the survival of less mitotically active cells. In follow-up biopsies, the presence of rhabdomyomatous differentiation can confound the histologic diagnosis. Furthermore, these differentiated tumors appear to be more resistant to chemotherapy, thus biopsy and positron emission tomography scans following chemotherapy and radiation may prevent unnecessary treatment. We report an unusual case of Wilms tumor in a 21- year-old man with rhabdomyomatous differentiation of pulmonary metastases after chemotherapy, which presented a challenge during frozen section diagnosis.

Primary cutaneous CD30+ T-cell lymphoproliferative disorder presenting as paraphimosis: a case report and review of the literature.

Primary cutaneous CD30+ T-cell lymphoproliferative disorders (PC-CD30+ LPD) as a group are one of the more common types of T-cell lymphoma. More specifically primary cutaneous anaplastic lymphoma (PC-ALCL), one of these lymphoproliferative disorders, is the second most common cutaneous T-cell lymphoma. We report an unusual presentation of PC-ALCL. A 90-year-old, uncircumcised male presented with a 3-week history of painful penile swelling and discharge. The patient was treated with cephalexin and underwent emergent circumcision for paraphimosis. The diagnosis of ALCL was made on microscopic evaluation of the foreskin along with follow-up staging studies. A literature review revealed 31 previously reported cases of penile lymphoma, one of which reported a primary penile CD30+ T-cell lymphoma similar to ours. Only one case report described a lymphoma presenting as paraphimosis. Our case is the second reported case of PC-ALCL of the penis and the first of its kind to present as paraphimosis. Lymphomas must be included in the differential diagnosis of penile lesions and paraphimosis. When present, clinicians should be able to differentiate primary cutaneous lymphoma from lymphomas with secondary skin involvement. All foreskins should be submitted to pathology for proper evaluation of penile lesions.

Potential utility of CD5 immunohistochemical staining in the diagnosis of muscle tumors.

CD5 is a 67 KD glycoprotein receptor that is present on a variety of T lymphocytes and mantle zone lymphocytes and is used routinely for the diagnosis of lymphomas and thymic carcinomas. That CD5 may be useful in diagnosis of mesenchymal tumors was an incidental finding in our sarcoma practice. This pilot study evaluated CD5 expression in benign and malignant muscle tumors in comparison to normal muscle. Search of our pathology database identified the following cases: leiomyomas (10), rhabdomyomas (3), leiomyosarcomas (33), and rhabdomyosarcomas (9). In some of these cases, non-neoplastic smooth muscle (10) and skeletal muscle (6) were identified adjacent to tumors. In addition, 3 cases were retrieved for non-neoplastic smooth muscle tissue that was unrelated to any tumor. Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded tissue blocks using a CD5 monoclonal antibody. Positive immunoreactivity to CD5 was determined as 2+ (moderate) to 3+ (strong) cytoplasmic brown staining. CD5 was strongly and diffusely expressed in non-neoplastic skeletal (6/6) and smooth (10/10) muscle adjacent to tumor. Focal areas of moderate staining were sometimes observed. CD5 was also strongly and diffusely expressed in 3 cases of smooth muscle tissue not adjacent to tumor. Immunoreactivity to CD5 was negative in rhabdomyomas (3/3), rhabdomyosarcomas (9/9), and high-grade leiomyosarcomas (27/27 cases). Leiomyomas (10/10) were CD5 positive but showed variable intensity within the same tumor. Low-grade leiomyosarcomas (6/6) exhibited variable CD5 expression. In conclusion, this pilot study suggests that CD5 staining may be used to differentiate benign muscle tissue from malignancy. Albeit our case series is limited, this study indicates potential utility of CD5 staining in diagnosis of muscle tumors.