Gholam R. Hafez

Treatment of severe Epstein-Barr virus-induced lymphoproliferative syndrome with ganciclovir: Two cases of after solid organ transplantation

A lymphoproliferative syndrome following organ transplantation has been described that results from infection with the Epstein-Barr virus (EBV) [1,2]. EBV infection in the immunosuppressed host can induce B-cell proliferation and clinical disease that varies from benign infectious mononucleosis to a fulminant polyclonal or monoclonal lymphoid proliferation [2-51. Successful treatment has been accomplished by reducing immunosuppression and initiating therapy with acyclovir [2,6-81. Recently, anti-B-cell antibodies have also been successfully employed in two children after HLA-mismatched bone marrow transplantation [9]. Despite the use of these modalities, treatment failures have occurred, especially if the lymphoproliferation is monoclonal [lo]. Ganciclovir, 9-(1,3-dihydroxy-2-propoxymethyl) guanine, is a powerful inhibitor of herpes viruses including herpes simplex virus, cytomegalovirus, varicella-zoster virus, and EBV [ll-141. In vitro assays have demonstrated that ganciclovir is more potent than acyclovir in inhibiting EBV virus and may be more effective in the treatment of this infection [13]. Experience with ganciclovir in patients with cytomegalovirus infections has demonstrated the drug’s efficacy and low incidence of side effects [15-181. To our knowledge, the use of ganciclovir in patients with the lymphoproliferative syndrome has not been reported. We describe two cases of a severe lymphoproliferative disorder with EBV infection following transplantation. Both patients received ganciclovir after a poor initial response to intravenous acyclovir and reduction of immunosuppression.

Schwann Cell Features in Neurotropic Melanoma

Schwann cell features were found on ultrastructural examination of a neurotropic melanoma (de novo type) of the lip. A neurotropic pattern of growth was retained in metastatic tumors in lymph nodes and lung. Melanin was not demonstrable in extra‐epidermal tumor cells.

Significance of apparent intratympanic meningiomas

Meningioma is the most common tumor of the central nervous system, but it has only been reported in 79 patients to involve the temporal bone. The 4 cases presented here show striking clinical similarity to a subgroup of 20 meningiomas reported to be entirely intratympanic; however, in each instance the extent, origin, and potential of the disease was not initially evident.

Anaplastic carcinoma of the thyroid with osteoclast‐like giant cells

An unusual malignant thyroid neoplasm with a morphologic resemblance to giant cell tumor of the bone is reported in a patient who presented with a rapidly growing thyroid mass and a history of pre‐existing goiter. The light and electron microscopic studies disclosed areas of differentiated follicular carcinoma with gradual transition to undifferentiated carcinoma. Pleomorphic spindle‐shaped cells and giant cells were accompanied by numerous osteoclast‐like multinucleated giant cells. Desmosomes and interdigitating cell surfaces were apparent in the differentiated as well as undifferentiated areas on electron microscopy. These findings support an epithelial rather than a mesenchymal origin for this neoplasm. Cancer 52:2122‐2128, 1983.

Angiosarcoma outcomes and prognostic factors: a 25-year single institution experience.

Objective:Angiosarcoma is an aggressive malignancy with endothelial differentiation and notoriously poor prognosis despite aggressive therapy. Limited data are available to guide management decisions. To address this limitation, we present a large retrospective analysis of angiosarcoma patients treated at a single institution over a 25-year period. Methods:To identify factors that impact angiosarcoma outcomes, we reviewed demographic, tumor, and treatment characteristics of angiosarcoma patients evaluated at the University of Wisconsin Hospital between 1987 and 2012. Results:The cohort included 81 patients diagnosed at ages 19 to 90 years (median, 67 y). Fifty-five (68%) patients presented with localized disease, whereas 26 (32%) presented with metastases. The primary sites were visceral/deep soft tissue (42%), head and neck/cutaneous (37%), breast (16%), and limbs in the setting of Stewart-Treves (5%). The 5-year overall survival was 40% with a median of 16 months. By univariate analysis, significant adverse predictors of survival included metastases at presentation, visceral/deep soft tissue tumor location, tumor size>5 cm, tumor necrosis, and the absence of surgical excision. A trend toward prolonged survival was observed with radiation therapy and for chemotherapy in patients with metastases. Age, sex, and prior radiation showed no correlation with survival. Conclusions:Our large single institution series confirms the poor prognosis of angiosarcoma, supports a central role for surgical excision in management, and highlights the need for novel therapies particularly in patients who present with metastatic disease.

Screening for occult nodal metastasis in squamous cell carcinoma of the vulva.

Metastases to inguinofemoral lymph nodes in patients with carcinoma of the vulva alter the prognosis and treatment of this disease. Our goal was to determine if immunohistochemical staining could reveal occult metastatic nodal disease not detected with routine hematoxylin and eosin staining. We retrospectively examined a total of 110 lymph nodes from 10 patients who had undergone lymph node dissection and found to have all negative nodes. Paraffin embedded lymph nodes were immunostained with a monoclonal antibody directed against multiple low-and high-molecular weight cytokeratins. Micrometastases were not detected in any lymph nodes examined with immunohistochemistry. All positive and negative controls yielded satisfactory results. It is concluded that immunohistochemistry with cytokeratin antibodies does not provide greater sensitivity than routine hematoxylin and eosin staining for the detection of nodal metastases in vulvar carcinoma.

Expression of angiopoietin-TIE system components in angiosarcoma.

Angiosarcoma is an aggressive malignancy of endothelial differentiation. Potential roles of the endothelial angiopoietin-tunica interna endothelial cell kinase (ANGPT-TIE) system in angiosarcoma diagnosis, pathogenesis, prognosis and treatment are undefined. To examine the expression and prognostic significance of angiopoietin-1, angiopoietin-2, TIE1 and TEK (TIE2) proteins in angiosarcoma, we immunohistochemically evaluated clinically annotated human angiosarcoma samples. Correlations of protein expression with overall survival and pathological features were explored. The cohort included 51 patients diagnosed with angiosarcoma at the age of 30–86 years (median 67). The 5-year overall survival was 45% with a median of 26 months. Moderate to strong expression of angiopoietin-1, TIE1 and TEK (TIE2) was identified in the majority of angiosarcomas and moderate to strong expression of angiopoietin-2 was observed in 42% of angiosarcomas. Increased angiopoietin-1 expression correlated with improved survival. Non-significant trends toward longer survival were also observed with increased TIE1 and TEK (TIE2) expression. Increased expression of angiopoietin-2, TIE1 and TEK (TIE2) was associated with vasoformative architecture. No differences in expression of these proteins were observed when patients were segregated by age, gender, presence or absence of metastases at diagnosis, primary tumor location, radiation association or the presence of necrosis. We conclude that components of the ANGPT-TIE system are commonly expressed in angiosarcomas. Reduced expression of these proteins is associated with non-vasoformative and clinically more aggressive lesions.

Acral lentiginous melanoma simulating "clear cell sarcoma of tendon and aponeuroses".

Clear cell sarcoma was closely mimicked in metastatic tumor deposits from two patients with acral lentiginous malignant melanoma. A subcutaneous deposit composed of glycogen‐laden spindle cells dominated the presenting clinical picture in one patient. In the other, primary acral melanoma resembled a histiocytic tumor and metastatic tumor simulated clear cell sarcoma. The cases illustrate the pleomorphism that may be encountered in malignant melanoma.

Extension of recurrent rectal carcinoma through sciatic foramen: Diagnosis by computed tomography

Abstract An elderly man presented with a gluteal mass and features of sciatic nerve compression 7 yr after a “curative” abdominoperineal resection for adenocarcinoma of the rectum. Computed tomography demonstrated local recurrence of the rectal carcinoma which extended through the sciatic foramen and resulted in these unusual presenting symptoms. The efficacy of computed tomography in the evaluation of local recurrence from rectal malignancy is emphasized.

Case of the season

A 20-YEAR-OLD healthy woman presented with a 6-week history of gradually enlarging left posterior shoulder mass. She denied pain or functional problems associated with the mass. She denied history of trauma or of any other lesions. On physical examination, there was a large, nontender, mobile soft-tissue mass measuring 5 × 2 cm in size lateral to the upper thoracic spine and just medial to the superior scapula. The overlying skin was normal without erythema or warmth. No lymphadenopathy was appreciated. The neurovascular examination in the left upper extremity was normal. Shoulder had full range of motion. Ultrasound examination is shown in Figure 1, and magnetic resonance imaging (MR1) is shown in Figure 2.