Fadi W. Abdul-Karim

Bone metastasis from gynecologic carcinomas: A clinicopathologic study

Between 1948 and 1984, autopsies were performed on 305 patients with primary carcinomas of the cervix, endometrium, ovaries, fallopian tubes, vulva, and vagina. Skeletal metastases were detected premortem and at autopsy in 49 cases (16.1%): cervix, 20 (40.8%); endometrium, 17 (34.7%); ovary, 7 (14.3%); vulva, 4 (8.2%); fallopian tube, 1 (2%). There were no cases of osseous metastasis from vaginal carcinoma. The incidence and sites of metastasis from these gynecologic carcinomas were correlated with their clinical and histopathologic classifications. This clinicopathologic study, based on autopsy data, demonstrates that osseous metastases are not uncommon, are significantly greater than clinically appreciated, and correlate with advanced anatomic stage and histopathologic type and grade.

Expression pattern of two Frizzled-related genes, Frzb-1 and Sfrp-1, during mouse embryogenesis suggests a role for modulating action of Wnt family members.

Wnt proteins have been implicated in regulating growth and pattern formation in a variety of tissues during embryonic development. We previously identified Frzb‐1, a gene which encodes a secreted protein with homology in the ligand binding domain to the Wnt receptor Frizzled, but lacking the domain encoding the putative seven transmembrane segments. Frzb‐1 has recently been shown to bind to Wnt proteins in vitro, and to inhibit the activity of Xenopus Wnt‐8 in vivo. We report now that mFrzb‐1 and Wnt transcripts display both complementary and overlapping expression patterns at multiple sites throughout embryonic development. By Northern analysis, the expression of mFrzb‐1 in the developing mouse embryo is greatest from 10.5 to 12.5 days postcoitum (dpc). In the early embryo, mFrzb‐1 is expressed in the primitive streak, presomitic mesoderm, somites, and brain. Later, mFrzb‐1 exhibits sharp boundaries of expression in the limb bud, branchial arches, facial mesenchyme, and in cartilaginous elements of the appendicular skeleton. We conclude from these experiments that Frzb‐1is expressed at a time and location to modulate the action of Wnt family members during development of the limbs and central nervous system. Dev. Dyn. 1998;212:364–372.

Open quiz solution: Case report 736

This 50-year-old woman presented with progressive pain in the left thigh. Radiographs showed a 9 x 6 cm soft-tissue mass located at the lateral border of the left femur. Magnetic resonance (MR) examination showed an eccentric, nonhomogeneous, soft-tissue mass abutting the femur. The preoperative differential diagnosis was schwannoma, low-grade neurogenic tumor, large periosteal ganglion, or fibroma. At operation, the cut surface of the specimen had features of an organizing hematoma with recent remote hemorrhage and areas of fibrosis. Histopathological examination confirmed the presence of polarizable foreign body material in a background of foreign body reaction. The specimen represented a retained surgical sponge which had been present since the patients surgery for a comminuted fracture 35 years earlier. Gossypiboma, or cotton balloma, is a term used to describe a mass within the body composed of cotton matrix. Radiopaque markers are now present on surgical sponges, and their appearances have been well documented. The gossypiboma, however, may still present a diagnostic problem if the marker is distorted by folding, twisting, or disintegration over a period of time. Without the radiopaque markers, retained sponges are difficult, if not impossible, to diagnose, as was the situation in this case.

Osteogenic sarcoma: Malignant fibrous histiocytoma subtype

A distinctly different entity from the now well‐delineated malignant fibrous histiocytoma (MFH) of bone is the MFH histopathologic subtype of osteogenic sarcoma. Although uncommon, recently the authors have encountered six cases of this neoplasm, in each of which the soft tissue component was devoid of bone elements and was microscopically indistinguishable from MFH of bone or soft tissue. Neoplastic osteoid and woven bone were present in the osseous component of each tumor, however. Radiologically, the lesions generally were osteoblastic but focally osteolytic with features typical of osteogenic sarcoma. Pain was the most common presenting symptom. There was no age or sex predilection. Immunocytochemical staining showed strong positivity with alpha‐1‐antichymotrypsin within malignant bizarre giant cells and occasional neoplastic osteoblasts in five cases. The biological behavior followed a very aggressive course. Four of the six patients developed pulmonary metastases 6 to 12 months after initial surgery; one patient presented initially with pulmonary metastases. Adequate tumor sampling as well as optimal correlation with clinical and radiographic information are required to distinguish the MFH subtype of osteogenic sarcoma from MFH of bone, both being high‐grade neoplasms, however.

Comparative Immunohistochemical Study of Insulin-like Growth Factor II and Insulin-like Growth Factor ReceptorType 1 in Pediatric Brain Tumors

Insulin-like growth factor (IGF)-II is an important growth factor in development of the central nervous system. The purpose of this study was to evaluate expression of IGF-II and IGF receptor type 1 (IGFR1) in various pediatric brain tumors. Immunohistochemistry for IGF-II and IGFR1 was performed on 15 choroid plexus papillomas (CPPs) including 1 atypical CPP, 2 choroid plexus carcinomas (CPCs), 5 anaplastic ependymomas, 7 nonanaplastic ependymomas (simply referred to as “ependymoma”), 5 medulloblastomas, 1 cerebral neuroblastoma, and 1 atypical teratoid/rhabdoid tumor (ATRT) along with 10 non-neoplastic choroid plexus and 3 non-neoplastic ependymal linings. All non-neoplastic choroid plexus, CPPs, CPCs, anaplastic ependymomas, ATRT, 71% of ependymomas, and 67% of non-neoplastic ependymal linings showed cytoplasmic positivity for IGF-II, whereas all medulloblastomas and the cerebral neuroblastoma were negative for IGF-II. In addition to cytoplasmic positivity for IGFR1, membranous positivity was observed in 73% of CPPs, both CPCs, the ATRT, 22% of non-neoplastic choroid plexus, 80% of anaplastic ependymomas, and 29% of ependymomas, but not in any medulloblastoma, cerebral neuroblastoma, or non-neoplastic ependymal lining. IGF-II and IGFR1 may play roles in the pathogeneses of CPP, CPC, anaplastic ependymoma, ependymoma, and ATRT. Immunohistochemical testing for IGF-II and IGFR1 may be useful in differentiating ATRT, CPC, and anaplastic ependymoma from medulloblastoma and cerebral neuroblastoma.

Histological Study of Injected Autologous Fascia in the Paralyzed Canine Vocal Fold

Objective Several methods have been used for the treatment of the unilateral paralyzed vocal fold. Teflon injections have been used e‐tensively but not without complications. The ideal substance for injection is yet to be determined. Injected autologous fascia has been reported as a means of achieving glottic closure. In review of the literature, there are no long‐term results described using autologous fascia in this way. The purpose of this study was to e‐amine the histological changes of the laryn‐ after injection of autologous fascia into a paralyzed vocal fold.

Isolated appendiceal metastasis in early ovarian carcinoma

The appendix was identified as the only site of extrapelvic metastatic ovarian carcinoma at the time of primary surgical staging. Isolated appendiceal metastasis has not been previously reported in comprehensively staged early stage ovarian carcinoma. Routine appendectomy during surgical staging of ovarian carcinoma should be considered. J. Surg. Oncol. 64:246–247, 1997

Pulmonary sequelae of intraparenchymal bismuth subgallate

Bismuth subgallate (BSG) is a heavy metal compound which is effective in lowering the incidence of hemorrhage after adenotonsillectomy and has been demonstrated to activate Factor XII. In a minority of children, the paste has been suctioned from the cuffless oral endotracheal tube after adenotonsillectomy. No pulmonary sequelae have been noted in these patients. To assess the effect of BSG aspiration, 75 rats were divided into groups receiving either intratracheal BSG or saline. Early and late parenchymal effects were documented at 5 and 30 days following administration. Although there were no differences in the general well‐being, activity level, or weight in these rats, acute pneumonia followed by a histiocytic, foreign‐body response was noted in a significant number of rats in the BSG group. Although no clinical pulmonary sequelae of BSG use have been noted in our patients, this information should alert clinicians to the risks of BSG use in the pulmonary‐compromised patient, and encourage them to either employ all methods of preventing aspiration in such patients when using BSG, or to use another hemostatic modality for the utmost safety.

Ribonucleotide reductase inhibition restores platinum-sensitivity in platinum-resistant ovarian cancer: a Gynecologic Oncology Group Study

BackgroundThe potent ribonucleotide reductase (RNR) inhibitor 3-aminopyridine-2-carboxyaldehyde-thiosemicarbazone (3-AP) was tested as a chemosensitizer for restored cisplatin-mediated cytotoxicity in platinum-resistant ovarian cancer.MethodsPreclinical in vitro platinum-resistant ovarian cancer cell survival, RNR activity, and DNA damage assays were done after cisplatin or cisplatin plus 3-AP treatments. Six women with platinum-resistant ovarian cancer underwent four-day 3-AP (96u2009mg/m2, day one to four) and cisplatin (25u2009mg/m2, day two and three) infusions every 21u2009days until disease progression or adverse effects prohibited further therapy. Pre-therapy ovarian cancer tissues were analyzed by immunohistochemistry for RNR subunit expression as an indicator of cisplatin plus 3-AP treatment response.Results3-AP preceding cisplatin exposure in platinum-resistant ovarian cancer cells was not as effective as sequencing cisplatin plus 3-AP together in cell survival assays. Platinum-mediated DNA damage (i.e., γH2AX foci) resolved quickly after cisplatin-alone or 3-AP preceding cisplatin exposure, but persisted after a cisplatin plus 3-AP sequence. On trial, 25 four-day overlapping 3-AP and cisplatin cycles were administered to six women (median 4.2 cycles per patient). 3-AP-related methemoglobinemia (range seven to 10%) occurred in two (33%) of six women, halting trial accrual.ConclusionsWhen sequenced cisplatin plus 3-AP, RNR inhibition restored platinum-sensitivity in platinum-resistant ovarian cancers. 3-AP (96u2009mg/m2) infusions produced modest methemoglobinemia, the expected consequence of ribonucleotide reductase inhibitors disrupting collateral proteins containing iron.Trial registryClinicalTrials.gov NCT00081276

Case report 664

A 9-year-old male child presented with a 2-month history of a painful mass over the left scapula. No antecedent t rauma was reported. He denied fever, chills, anorexia, weight loss, or constitutional symptoms. He had experienced an unusually prolonged, severe case of varicella infection at age 6 years which resolved without antiviral therapy. Physical examination was unremarkable except for an ill-defined, tender, nonfluctuant, soft-tissue