A comparison of the histopathologic features of thyroid carcinomas with NTRK fusions to those with other malignant fusions.

BACKGROUND: Chromosomal rearrangements involving one of the NTRK genes result in oncogenic driver mutations in thyroid carcinoma (TC) and serve as a target for therapy. We compared the clinicopathologic features of thyroid carcinomas with NTRK fusions vs. thyroid neoplasms with other malignancy associated gene fusions within our institution. MATERIALS AND METHODS: Our pathology archives were searched from 2013 to 2023 for thyroid neoplasms with gene fusions, excluding THADA fusions and medullary thyroid carcinomas. RESULTS: 55 thyroid lesions were identified: 22 with NTRK fusions (NTRK cohort) and 33 with other fusions (non-NTRK cohort). On fine needle aspiration (FNA), 54% of the NTRK cohort were classified as Category V as per Bethesda System for Reporting Thyroid Cytology (TBSRTC) and 51.5% of non-NTRK cohort as TBSRTC Category III. In the NTRK cohort, the most common reported fusion was ETV6::NTRK3 and the most common reported fusion in the non-NTRK cohort was PAX8::PPAR-gamma. On histologic examination both cohorts were most commonly diagnosed as PTC follicular variant. Invasive features were more common in the NTRK cohort in comparison to the non-NTRK cohort. Locoregional recurrence occurred in 2/22 NTRK cases and 2/33 non-NTRK cases, with average time from surgery to recurrence being 5.5 months and 21 months, respectively. The majority of patients in both groups are alive with no evidence of disease. CONCLUSIONS: Thyroid neoplasms with a malignancy associated gene fusion are likely to be diagnosed as subtype/variant of PTC. Patients whose thyroid lesions harbor NTRK fusions present with a PTC-FV that on presentation has more aggressive clinicopathologic findings and are likely to have earlier disease recurrence.

Differentiated high grade thyroid carcinomas: Diagnostic consideration and clinical features.

BACKGROUND: Differentiated high-grade thyroid carcinomas (DHGTCs) are a new diagnostic entity most recently defined in the 2022 World Health Organization's (WHO) Classification of Endocrine and Neuroendocrine Tumors. This new entity has been minimally described in the literature, and additional cases classified as such are missing. MATERIALS AND METHODS: Cases of DHGTCs diagnosed at our institution from 2012 to 2022 were identified, and the following were reviewed: cytologic and histologic diagnoses, ancillary testing, immunohistochemical staining, treatments, and patient outcomes. Immunohistochemical staining for Ki67 was performed on selected cases lacking this immunostain. A systematic literature review of the English literature on DHGTCs from 2013 to 2023 was performed using PubMed and Embase. RESULTS: Case cohort included 32 cases of DHGTCs, with an average age of 52.6 years (range 17-84 years) and a male:female ratio of 1.3:1. All cases underwent fine needle aspiration (FNA) and were categorized by The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) as follows: 14 cases as malignant (43.8 %), 10 as follicular neoplasm (31.3 %), 5 as atypia of undetermined significance (15.6 %), 2 as suspicious for malignancy (6.2 %), and 1 as non-diagnostic (3.1 %). The average tumor size was 5.15 cm, and most were papillary thyroid carcinoma (28, 87.5 %), with classic subtype being the most common. Twenty-one cases revealed tumor necrosis and the mitotic activity in lesions without necrosis averaged to 5.5 mitoses per 2 mm2 (range 0-7). The average Ki67 proliferative index was 5.6 %. Extrathyroidal extension was seen in 17, angioinvasion in 21, lymphatic invasion in 7, and perineural invasion in 1 case. Foci of solid or trabecular growth were identified in five cases. Lymph node metastases at the time of diagnosis were noted in 10 cases and 7 demonstrated distant metastases or locoregional recurrence. To date, 25 patients are alive, and one has died from disease. CONCLUSIONS: Our institutional experience demonstrates that DHGTC is a rare, but aggressive thyroid tumor subtype that requires consideration in the setting of a well-differentiated thyroid neoplasm to appropriately assess for possible disease recurrence and determination of patient prognosis.

An investigation into noninvasive follicular thyroid neoplasms with papillary-like nuclear features: does the initial proposal on noninvasive follicular thyroid neoplasms with papillary-like nuclear features behavior hold true?

Current management of patients with noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) is lobectomy with close clinical follow-up. Because this entity is still young, we present our 5-year institutional experience with NIFTP since that time. Cases of NIFTP diagnosed from 2017 to 2022 were identified. Data points including patient demographics, radiology, cytologic and pathologic diagnoses, molecular profiles, and clinical follow-up were documented. A literature review of NIFTP case series was performed. A total of 379 cases were included (mean age: 52 years, female:male ratio 3.3:1). Ultrasound findings were available for 260 patients, and 247 underwent fine-needle aspiration (FNA). The FNA diagnoses per the Bethesda System for Reporting Thyroid Cytology were nondiagnostic (n = 2), benign (n = 16), atypia of undetermined significance/follicular lesion of undetermined significance (n = 119), follicular neoplasm/suspicious for follicular neoplasm (n = 68), suspicious for malignancy (n = 31), and malignant (n = 11). Molecular testing was performed in 179 cases. Lobectomy was performed for 183, total thyroidectomy for 192, and nodulectomy for 4 cases. The average size of NIFTP was 2.3 cm, and 232 cases had additional nodules (including benign and malignant neoplasms). Multifocal NIFTP occurred in 32 patients. Lymph nodes were evaluated in 196 cases with metastatic carcinoma in 29 cases (all with concurrent diagnoses of carcinoma). Most patients were alive at follow-up, 100 were lost to follow-up, and three died from other causes. Literature review revealed 2870 NIFTP cases with similar patient demographics and pathologic findings. We confirm that NIFTP is a low-risk neoplasm with indolent clinical behavior, which can be managed conservatively.

Carcinogenesis in human skin grafted to SCID mice.

To directly examine a multistage carcinogenesis model and the role of UV light in human tissues, we grafted human skin onto mice with severe combined immunodeficiency disease. We found that the maximum dose of UV radiation in the B range (UVB; 280-320 nm) tolerated by these grafts was 500 J/m2 three times weekly. One hundred fifty-one grafted mice were then randomized and observed for a median of 9 months in five groups: no treatment, chemical initiation alone, UVB as a complete carcinogen, initiation plus UVB promotion, and initiation plus UVB and phorbol ester promotion. Actinic damage and squamous atypia were found in grafts of all groups receiving UV treatment; unequivocal human squamous carcinomas developed in two of these. Species origin was verified by human-specific bisbenzimide staining and in situ hybridization for human-specific Alu segment. Overall basal proliferation, measured immunohistologically, was reduced in UV-treated grafts, but foci of hyperproliferation were seen in conjunction with the dedifferentiated expression of cytokeratins 1, 10 and 5, 8. Murine tumors also developed frequently, confirming the biological relevance of the carcinogenic strategies tested. These findings demonstrate that development of malignant human tumors can be experimentally accelerated in human tissue.

Expression of prolactin and its receptor in human breast carcinoma.

The growth regulatory effects of PRL on the human breast are mediated by its receptor (PRLr), a member of the cytokine receptor family. Recent reverse transcriptase-PCR studies by our laboratory and others have shown PRL expression within breast tissues at the RNA level. To confirm the role of this growth factor-receptor complex in normal and malignant breast tissues, the expression of PRL and PRLr was examined in parallel with the estrogen receptor (ER) and progesterone receptor (PR). Sixty-nine cases of primary invasive breast carcinoma were examined for PRL and PRLr expression by in situ hybridization and immunohistochemical technique, respectively. These data revealed widespread expression of PRL and its receptor in the breast cancers studied (>95%) and in the normal breast tissues (>93%), with no association between the expression of PRL-PRLr and ER or PR. These findings stand in contrast to prior RIA-based studies that detected the PRLr in only 20-60% of breast carcinomas, most commonly in ER-PR-positive cells. These results confirm prior data indicating the presence of an autocrine/paracrine loop for the PRL-PRLr complex within human breast tissues. Given the widespread expression of PRL-PRLr in breast cancer, pharmacological interventions aimed at the inhibition of function of this growth regulatory receptor complex may be of considerable utility in the therapy of this disease.

Fetal akinesia deformation sequence (Pena-Shokeir phenotype) associated with acquired intrauterine brain damage.

An infant with Pena-Shokeir phenotype was born to a cocaine-using mother. The pathologic findings included polyhydramnios, facial anomalies, arthrogryposis, camptodactyly, pulmonary hypoplasia, and tetralogy of Fallot. The neuropathologic findings were diffuse brainstem and spinal cord neuronal degeneration and focal cerebral infarction, consistent with acquired intrauterine ischemic damage.

Epstein-Barr virus-associated hepatic smooth muscle neoplasm in a cardiac transplant recipient.

Host immunosuppression is increasingly recognized as a significant risk factor for the development of a primary neoplasm. Chronic immunosuppressive therapy, as used in organ transplantation, may perturb the immunosurveillance ability of the host, making the patient more susceptible to virus-associated malignancies. We have taken care of a care of a child who received an orthotopic heart transplant and who then developed both a generalized lymphoproliferative disorder and a leiomyoma of the liver a year later. Epstein-Barr virus DNA was detected in a lymph node initially and the hepatic tumor cells subsequently. The former responded to a reduction in the immunosuppressive medications and the latter responded to surgical resection. This is the first report of a hepatic smooth cell neoplasm occurring following cardiac transplant and the development of two sequential Epstein-Barr virus-associated disorders in an immunosuppressed patient.

A recent decrease in the time to development of monomorphous and polymorphous posttransplant lymphoproliferative disorder.

We have noted a decrease in the time to development of posttransplant lymphoproliferative disorder (PTLD) over the last two and one-half years in our multiorgan transplant program. From February 1965 until December 1990, 1622 transplants were performed including 1489 kidneys (KTxp), 87 livers (LTxp), and 46 pancreata. Between February 1965 and July 1988 (group 1), there were 1260 transplants performed and nine cases of either monomorphous PTLD (M-PTLD, n = 8) or polymorphous PTLD (P-PTLD, n = 1) were diagnosed. The mean time to development of PTLD was 163 +/- 128 weeks, all after KTxp. Five of these nine patients received haploidentical living-related grafts. All patients had presented with advanced disease, none had transplant nephrectomy, and all died of their disease. Between July 1988 and December 1990 (group 2), 362 transplants were performed, and four cases of M-PTLD and three cases of P-PTLD were recognized. Of the seven cases of PTLD in group 2, six developed within 90 days posttransplant (early PTLD). The mean time to development of PTLD was 11 +/- 16 weeks. This was significantly earlier than group 1 (P less than .01). Four of the five cases after KTxp had a 1 or 2 DR-matched donor. Five of these seven patients had serological evidence of recent Epstein-Barr Virus infection, and four of these five had received OKT3 and then developed early PTLD. In group 2, three patients are alive 7-15 months after KTxp nephrectomy, the remaining four have died. We hypothesize that risk factors for the development of PTLD may include heavy immunosuppression, including the use of OKT3, good DR matching, and active EBV infection. Treatment should include graft removal, if applicable, and reduction or cessation of immuno-suppression.

Reduction in immunosuppression as initial therapy for posttransplant lymphoproliferative disorder: analysis of prognostic variables and long-term follow-up of 42 adult patients.

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is an Epstein-Barr virus-associated malignancy that occurs in the setting of pharmacologic immunosuppression after organ transplantation. With the increased use of organ transplantation and intensive immunosuppression, this disease is becoming more common. We explore reduction in immunosuppression as an initial therapy for PTLD. METHODS: We analyzed our organ transplant patient database to identify patients with biopsy-proven PTLD who were initially treated with reduction of their immunosuppressive medications with or without surgical resection of all known disease. RESULTS: Forty-two adult patients were included in this study. Thirty patients were treated with reduction in immunosuppression alone. Twelve patients were treated with both reduction in immunosuppression and surgical resection of all known disease. Thirty-one of 42 patients (73.8%) achieved a complete remission. Of those patients who were treated with reduction in immunosuppression alone, 19 of 30 (63%) responded with a median time to documentation of response of 3.6 weeks. Multivariable analysis showed that elevated lactate dehydrogenase (LDH) ratio, organ dysfunction, and multi-organ involvement by PTLD were independent prognostic factors for lack of response to reduction in immunosuppression. In patients with none of these poor prognostic factors, 16 of 18 (89%) responded to reduction in immunosuppression in contrast to three of five (60%) with one risk factor and zero of seven (0%) with two to three factors present. The analysis also showed that increased age, elevated LDH ratio, severe organ dysfunction, presence of B symptoms (fever, night sweats, and weight loss), and multi-organ involvement by PTLD at the time of diagnosis are independent prognostic indicators for poor survival. With median follow-up of 147 weeks, 55% of patients are alive with 50% in complete remission. CONCLUSIONS: Reduction in immunosuppression is an effective initial therapy for PTLD. Clinical prognostic factors may allow clinicians to identify which patients are likely to respond to reduction in immunosuppression.

Cortactin localization in actin-containing adult and fetal tissues.

Cortactin is a tyrosine kinase substrate that binds to filamentous actin. It represents a highly conserved family of perimembrane signaling proteins. The human homologue of cortactin is encoded by gene EMS1, which is amplified in some human breast, head, and neck carcinomas. This study shows that cortactin is preferentially localized to the apical surfaces of the polarized epithelium, specifically, to the terminal web of small bowel epithelium and to apical surfaces of the proximal renal tubules, thyroid follicles, and bronchiolar epithelium. Cortactin is also seen in cell and tissue types with actin-based contractile capacities, including smooth and striated muscle and myoepithelium.

Ret oncogene activation in papillary thyroid carcinoma: prevalence and implication on the histological parameters.

The Ret proto-oncogene is known to be rearranged in papillary carcinoma of the thyroid. The aim of this study was to investigate the in situ expression of Ret mRNA in thyroid tumors. Formalin-fixed, paraffin-embedded tissue specimens from 45 thyroid lesions were examined by in situ hybridization using manual capillary action technology (MicroProbe Staining System) and a 52-base synthetic biotinylated oligonucleotide probe complementary to the tyrosine-kinase domain of Ret proto-oncogene. The clinicopathological features of these patients with thyroid lesions also were noted. Ret was noted in 17 (43%) of 40 papillary carcinomas. In contrast, none of the three follicular carcinomas, follicular adenoma, nodular hyperplasia, and normal thyroids, showed evidence of Ret mRNA. Our results showed that, in papillary thyroid carcinoma, there is an important role of Ret activation. The Ret staining could be a useful marker for papillary carcinoma.

Diagnosis of posttransplantation lymphoproliferative disorder by endomyocardial biopsy in a cardiac allograft recipient.

Posttransplantation lymphoproliferative disorder is a serious complication of organ transplantation. This disorder has been linked to Epstein-Barr virus infections and can involve the transplanted organ. In the past the diagnosis of posttransplantation lymphoproliferative disorder in heart transplant recipients involving the transplanted organ was made primarily at autopsy. A case of a patient with posttransplantation lymphoproliferative disorder in whom the diagnosis was made initially by endomyocardial biopsy with confirmation by application of molecular techniques on mediastinal lymph node tissue and who was subsequently treated successfully is reported.

Rapid method for detection of Aspergillus 5S ribosomal RNA using a genus-specific oligonucleotide probe.

Ribosomal RNA (rRNA) is present in all prokaryotic and eukaryotic cells. Although sequences are conserved, variations in nucleic acid composition are known to be species specific. Formalin or Bouin's fixed, paraffin-embedded tissue specimens from 17 cases of culture proven Aspergillus sp infections were studied by a rapid (< 30 minutes) in situ hybridization procedure using a biotinylated oligonucleotide DNA probe complementary to nucleic acids 1-22 of Aspergillus sp 5S rRNA sequence. Positivity was noted within fungal organisms in all 17 cases and was identified in both hyphal forms and within fruiting bodies. Signal was weak or absent within the center of Aspergillus abscess cavities with increasing signal located toward the periphery of the cavity, suggesting that rRNA in situ hybridization may detect viable fungal forms. In situ hybridization with the oligonucleotide probe on tissues containing several different organisms including Candida sp, Histoplasma capsulatum, Cryptococcus neoformans, Pneumocystis carinii, Pseudallescheria boydii, Fusarium sp, and Mucor were negative. Use of site specific oligonucleotide probes specific for a variety of rRNA sequences may aid in the diagnosis of several medically important bacterial, fungal, and protozoal pathogens.

Sensitivity and specificity of antibodies on necrotic tumor tissue.

Immunohistochemistry occasionally is used to determine the lineage of entirely necrotic tumors. However, the sensitivity and specificity of antibodies on necrotic tissue are unknown. To determine the usefulness of immunohistochemistry with necrotic lesions, a series of 24 known tumors consisting of 14 carcinomas, 2 lymphomas, 2 melanomas, and 6 sarcomas (all with extensive necrosis) was examined for reactivity with 6 cytokeratin antibodies, S100, and LCA. Carcinomas stained positively with at least 1 cytokeratin antibody in 78% of the cases. The cytokeratin antibodies with the highest sensitivity were AE1, AE1/3, S903, and PANCK. These antibodies also retained specificity for epithelial differentiation; no reactivity was observed in the 10 necrotic nonepithelial tumors. LCA retained its reactivity with necrotic lymphoma, but S100 reacted with only one third of the necrotic lesions. Unexpectedly, reactivity for LCA and S100 occurred in some necrotic carcinomas. Keratin markers can be used on necrotic tissue to determine epithelial differentiation, but the results obtained with S100 and LCA on necrotic tissue should be interpreted with caution.

Hepatosplenic gamma-delta T-cell lymphoma as a late-onset posttransplant lymphoproliferative disorder in renal transplant recipients.

We report 2 cases of renal transplant recipients in whom hepatosplenic gamma-delta T-cell lymphoma (gamma-delta HSTCL) developed 5 and 10 years after transplantation. Both patients had marked hepatosplenomegaly, B symptoms (weight loss, fever, and night sweats), and abnormal peripheral blood findings, including anemia in both, thrombocytopenia and leukoerythroblastic changes in 1, and leukocytosis in the other. Markedly atypical lymphoid infiltrate of intermediate to large cells was observed in the spleen, liver, and bone marrow. The malignant cells showed typical immunophenotype of gamma-delta T cells (CD2+, CD3+, CD4-, CD8-, CD7+, gamma-delta T-cell receptor-positive, and alpha-beta T-cell receptor-negative) with clonal T-cell receptor gene rearrangement and were of the V-delta-1 subset. In addition, the cells contained a cytolytic granule-associated protein, TIA-1, and Fas ligand, indicating cytotoxic T-cell differentiation. The malignant T cells in both cases were of host tissue origin. Both cases were negative for Epstein-Barr virus genome using Southern blot analysis. The patients did not respond to reduction of immunosuppression. Despite initial response to chemotherapy, both patients died within 6 months of diagnosis. Our findings indicate that gamma-delta HSTCL can occur as a late complication in transplant recipients.

Characterization of natural occurring Pneumocystis carinii pneumonia in pigs by histopathology, electron microscopy, in situ hybridization and PCR amplification.

Macroscopic, histologic, ultrastructural, microbiologic, in situ hybridization (ISH) and PCR detection results in three 8-week-old pigs naturally infected with Pneumocystis carinii (PC) are described. All animals had a nonsuppurative interstitial pneumonia and intra-alveolar Pneumocystis organisms with foamy eosinophilic and PAS positive appearance. Ultrastructurally, PC trophozoites and cysts were observed in pigs No. 2 and No. 3, with the former being much more numerous. PC organisms were located on the alveolar surface or within the alveolar septa. Trophozoites had numerous filopodia and were thick-walled. Cysts had no or few filopodia, were thick-walled and contained intracystic bodies. Using non-isotopic ISH on formalin-fixed, paraffin-embedded lung tissue sections, PC DNA from pigs No. 2 and No. 3 hybridized with a probe specific for PC ribosomal RNA (rRNA). Using primers specific for mitochondrial rRNA gene (pAZ102-E/pAZ102-H), and for the internal transcriber spacers of ribosomal gene of PC, PCR methods amplified a product in the lung of pigs No. 2 and No. 3 using either frozen or formalin-fixed and paraffin-embedded lung tissue. DNA from Pig No. 1 samples did not amplify with any primer. This is the first time that molecular biology techniques (in situ hybridization and PCR) have been applied to the study of porcine pneumocystosis.

Analysis of Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder after lung transplantation.

BACKGROUND: Epstein-Barr virus (EBV)-associated posttransplantation lymphoproliferative disorder (PTLD) is a serious complication of lung transplantation. Besides immunosuppression the risk factors for PTLD development are largely unknown. METHODS: The incidence of PTLD was ascertained in a lung transplant population consisting of 45 patients. Nine patients (20%) experienced PTLD. The clinical, histologic, and human leukocyte antigen (HLA) data were collected on all patients. The incidence of EBV infection in lymphoid tissue taken at the time of engraftment was studied by using EBV in situ hybridization. RESULTS: All patients with PTLD had polymorphous lymphoproliferations, seven of which were polymorphous B-cell hyperplasias and two of which were polymorphous B-cell lymphomas. EBV was identified in all lesions. All patients with polymorphous B-cell hyperplasias had clinically unsuspected disease, five of which were identified at autopsy. The two polymorphous B-cell lymphoma lesions were monoclonal and regressed with immunosuppression reduction. EBV in situ hybridization on donor or recipient lymph nodes obtained at engraftment from the 45 transplant recipients showed no difference in the number of EBV positive cells in patients with and without PTLD. Cyclosporine and PTLD and azathioprine dosages and cyclosporine levels were similar between patients with and without PTLD. PTLD was seen in patients with high cumulative doses of antilymphocyte globulin. Analysis of HLA status showed a predominance of HLA A2 and DR7 in the donors of the patients with PTLD, whereas donor HLA B7 was more common in patients without PTLD> CONCLUSIONS: Detailed studies are necessary to further elucidate the risk factors for PTLD development in the lung transplant population.

Detection of Aspergillus ribosomal RNA using biotinylated oligonucleotide probes.

Aspergillosis continues to be a devastating disease entity that results in significant mortality in immunosuppressed patients. Rapid diagnosis is often required to initiate appropriate therapy. Although the histopathologist may be able to visualize fungal organisms in tissue specimens, the histology of Aspergillus species may overlap with a variety of fungi, so diagnosis often relies on fungal cultures that can take weeks to complete. Recently, an in situ hybridization assay targeting Aspergillus 5S ribosomal RNA (rRNA) was reported. This assay proved to be useful when fungal cultures were negative or not performed but when fungi compatible with Aspergillus species were identified in tissue sections. That study was performed to compare the probe described in the previous study (5S-1 probe) with two other probes specific for Aspergillus. Two customly designed 21- and 23-base oligonucleotide probes complementary to 5S (5S-2 probe) and 18S (18S-1 probe) rRNA of Aspergillus were synthesized and labeled with multiple biotin moieties at the 3' termini. By GenBank analysis, the sequence of the 18S-1 probe was shown to have 90% to 100% homology to Aspergillus fumigatus group, Aspergillus flavus, Aspergillus niger, Aspergillus terreus, Aspergillus parasiticus, Aspergillus tamarii, and Aspergillus glaucus group; the 5S-2 probe was homologous to Aspergillus flavus, Aspergillus niger, Aspergillus nidulans, Aspergillus awamori, and Aspergillus wentii. In situ hybridization was performed on 43 cases of Aspergillus infection including 41 localized aspergillomas in the lung, brain, sinonasal tract, and ear, and 2 cases of invasive aspergillosis involving pleura and soft tissue of the scapular region. The results were compared with those obtained using a previously reported 5S-1 probe. In situ hybridization was positive in 38, 38, and 40 cases with the 5S-1, 5S-2, and 18S-1 probes, respectively. The 18S-1 probe was most useful because of a wider detection spectrum. In situ hybridization for Aspergillus rRNA provides a useful means for rapidly and accurately identifying Aspergillus in tissues and may be useful if fungal organisms suggestive of Aspergillus species are present but if cultures are negative or have not been performed.

Chromosome analysis and comparison of the benign cystic and malignant squamous component of an ovarian teratoma.

Teratoma, the most common ovarian germ-cell tumor, presumably arises from a single germ cell and is composed of tissues representing all germ layers (ectoderm, mesoderm, and endoderm). Benign cystic teratomas (dermoid cyst) represent over 95% of ovarian teratomas and are comprised of entirely mature adult tissues. When malignant, almost all mature teratomas contain squamous carcinoma. We report for the first time the karyotypic comparison of an ovarian teratoma in a 36-year-old female with tissue separately taken from the benign cystic and malignant squamous components. The malignant squamous component revealed two distinct karyotypic populations: one diploid and the other polyploid. Both, however, demonstrated two common markers. The polyploid population also demonstrated numerous additional abnormalities with multiple copies of chromosome 20. Though many of the chromosomal aberrations were unique to the benign component, several karyotypes showed the same markers noted in the malignant squamous component. The significance of this finding is that it may serve to identify those histologically benign teratomas destined to undergo malignant transformation.

Cervical thorium dioxide granuloma ('thorotrastoma').

An elderly woman had an expanding cervical mass that entrapped and compressed the adjacent cranial nerves, blood vessels, and muscles. The mass was dense on radiographs, extended from the skull base to low neck in the prevertebral and parapharyngeal tissues, and showed mixed intensity on MR. A previous direct carotid arteriogram with thorium dioxide as the contrast agent suggested the histologically proved diagnosis of a cervical thorium dioxide granuloma ("thorotrastoma").