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Biomedical subjects

M Brandwein

Publications and source records attributed to M Brandwein.

At least 19 recordsLinked to original sources
PubMed2001

Significance and management of thyroid lesions in lymph nodes as an incidental finding during neck dissection.

BACKGROUND: The incidental discovery of thyroid lesions in lymph nodes during a lymph node dissection performed for a separate primary head and neck tumor is an unusual clinical entity. Its discovery has led to controversy regarding its significance and management. METHODS: We identified five patients over the years 1991-1999 with this finding. All five patients were subsequently treated with a total thyroidectomy and a level VI lymph node dissection. RESULTS: Pathological examination revealed three papillary carcinomas and level VI lymph node metastases in the two patients who had carcinoma in their thyroid glands. All five patients are presently free of their primary and thyroid disease on follow-up examinations. CONCLUSIONS: These patients should be addressed with additional work-up and surgery if metastatic thyroid cancer is documented in the lymph node. We offer a diagnostic algorithm that may aid in further work-up and treatment in these unusual cases.

Adult↗
PubMed2001

Ramification amplification: a novel isothermal DNA amplification method.

We have developed a novel isothermal DNA amplification method with an amplification mechanism quite different from conventional PCR. This method uses a specially designed circular probe (C-probe) in which the 3' and 5' ends are brought together in juxtaposition by hybridization to a target. The two ends are then covalently linked by a T4 DNA ligase in a target-dependent manner, producing a closed DNA circle. In the presence of an excess of primers (forward and reverse primers), a DNA polymerase extends the bound forward primer along the C-probe and displaces the downstream strand, generating a multimeric single-stranded DNA (ssDNA), analogous to the "rolling circle" replication of bacteriophages in vivo. This multimeric ssDNA then serves as a template for multiple reverse primers to hybridize, extend, and displace downstream DNA, generating a large ramified (branching) DNA complex. This ramification process continues until all ssDNAs become double-stranded, resulting in an exponential amplification that distinguishes itself from the previously described nonexponential rolling circle amplification. In this report, we prove the principle of ramification amplification. By using a unique bacteriophage DNA polymerase, Ø29 DNA Polymerase, that has an intrinsic high processivity, we are able to achieve significant amplification within 1 hour at 35 degrees C. In addition, we applied this technique for in situ detection of Epstein-Barr viral sequences in Raji cells.

Cell Line↗
PubMed2000

Lymphatic malformation: predictive factors for recurrence.

OBJECTIVE: Although lymphatic malformations are often found to be well circumscribed when surgery is undertaken in early childhood, complete surgical excision can be difficult when the lesion is infiltrative. This study retrospectively evaluates these patients in an attempt to identify prognostic factors that may predict recurrence. STUDY DESIGN AND SETTING: A retrospective chart review was conducted covering the years 1991 to 1998. Seventeen patients were identified having undergone 32 surgical resections of tumors described as lymphatic malformations. Data abstracted from the charts included the site of the lesion, surgical and histologic assessment of encapsulation, and status at follow-up examination. RESULTS: Six of 17 patients developed a recurrence after surgery. Correlation between recurrence and histologic or operative impressions of encapsulation was significant by chi(2) analysis (P<0.01). CONCLUSION: On the basis of the findings of this case series, lymphatic malformations that are found to be nonencapsulated and infiltrative by intraoperative or histologic assessment are more likely to recur.

Adolescent↗
PubMed2000

A clinicopathological study of sinonasal neuroendocrine carcinoma and sinonasal undifferentiated carcinoma.

OBJECTIVE: Sinonasal undifferentiated carcinoma (SNUC) and sinonasal neuroendocrine carcinoma (SNEC) are relatively newly recognized, rare entities requiring further clinicopathological analysis to advance our understanding and determine prognostic distinctions between them. STUDY DESIGN: Retrospective chart review. METHODS: Cases were retrieved from the Copath system. One patient was seen in consultation from an outside institution. Histological and immunohistochemical findings, patient demographics, treatment regimens, and outcomes were analyzed and compared. RESULTS: Ten patients (7 men, 3 women) ranging in age from 17 to 58 years (mean age, 44.7 y) were included. Four patients were classified with SNEC, six as having SNUC. The predominant site was the superior nasal cavity or ethmoids (seven cases), followed by the maxilla (four cases). Disease in four patients was clinically staged as N1 (three with SNUC, one with SNEC), and in six patients as NO (three with SNEC, three with SNUC). Of the nine patients who were treated initially with surgical resection, seven received postoperative radiation therapy alone, one received postoperative radiation and chemotherapy, and one had only limited postoperative chemotherapy. One patient was treated with radiation therapy and chemotherapy alone, without surgical resection. Follow-up was obtained ranging from 6 to 108 months (mean period, 26.4 mo). Three patients died of disease 10, 14, and 41 months, respectively, after diagnosis. Three patients had persistent disease at 6, 9, and 21 months, respectively, two of them with distant metastases. Four patients were disease free after 6, 18, 31, and 108 months, respectively. CONCLUSIONS: SNUC and SNEC are both aggressive tumors, usually presenting in middle age as a nasal mass. Both tumors have the capacity to metastasize locally and distantly, and both can result in poor outcomes. This small series precludes a demographic or prognostic distinction between the two groups.

Adolescent↗
PubMed1999

Malignant melanomas of the parotid: comparison of survival for patients with metastases from known vs unknown primary tumor sites.

BACKGROUND: Malignant melanoma (MM) rarely affects the parotid, and usually this diagnosis will herald a search for a primary skin neoplasm. Occasionally, no primary tumor is ever found, raising questions regarding prognosis and the issue of primary melanoma of the parotid. OBJECTIVE: To evaluate retrospectively the clinical and histological features of MM involving the parotid in 19 patients. DATA SOURCES: Pathology and hospital files at 3 tertiary care university hospitals. STUDY SELECTION: Patients with MM within the parotid with adequate histopathologic and immunohistochemical documentation, as well as clinical information regarding patient outcome. DATA EXTRACTION: In 6 patients, no extraparotid MM was ever identified. After parotidectomy, 5 patients (including 1 patient who died of other causes) were melanoma free at a mean of 4.2 years (range, 14 months to 7.5 years). Only 1 patient died of disease after 17 months. An extraparotid primary tumor was present in 13 patients, 10 with dermal and 3 with mucosal sites. At follow-up, only 1 of these patients was disease free after 2 years. Nine patients died of melanoma after a mean of 2.6 years (range, 10 months to 5 years); the other 3 had evidence of metastatic disease at a mean of 4.3 years (range, 3-6 years). Nondermal sites of primary tumors were the nasal cavity, sclera, and conjunctiva. DATA SYNTHESIS: Patients with metastatic MM from unknown primary tumors have a longer disease-free survival than those with metastases from known primary disease. CONCLUSIONS: Although rare, MM should be considered in the differential diagnosis of parotid tumors. Unusual mucosal or ocular sites should be considered in the search for possible primary tumor sites to avoid treatment delay. These data support the idea that patients with metastatic MM from unknown primary tumors may follow a more improved course than that of patients with metastases from known primary disease.

Adult↗
PubMed1999

Granular cell tumor of the parotid.

A case of granular cell tumor of the major salivary glands is presented. This tumor appeared as an expansive multinodular mass that arose from facial nerve trunks. The presenting symptoms of facial pain and paresis and the intraoperative findings of tumor adhesion to nerves led to the clinical impression of malignancy. At intraoperative consultation, the tumor resembled an acinic cell carcinoma. Pathologists should be aware that granular cell tumors may involve the major salivary glands and that it should be considered in the diagnostic differential diagnosis.

Female↗
PubMed1999

Sialoblastoma: clinicopathological/immunohistochemical study.

Sialoblastoma is an extremely rare salivary tumor diagnosed at birth or shortly thereafter with significant variability in histologic range and clinical course, so that for an individual case it may be difficult to predict the most appropriate therapy. We detail the case of a toddler noted to have a firm 1-2-cm mass in the left cheek at 21 months. Parotidectomy was performed at 26 months, revealing a sialoblastoma; the resection margins were positive. During the next 10 months, the mass recurred or persisted, necessitating numerous procedures. The tumor was composed of basaloid cells with fine chromatin and other more mature cuboidal epithelial cells. Ductules and solid organoid nests with some tendency toward peripheral pallisading were also noted. There was no perineural invasion; necrosis initially was sparse but increased over time. The mitotic rate also increased from 6 to 7/10 high-power fields in the first resection to 20/10 high-power fields in the last resection. Nuclear pleomorphism increased with time. The MiB1 proliferative index revealed a dramatic increase in the number of labeled nuclei: from 3 cells/10 high-power fields in the first specimen to 94 cells/10 high-power fields for the last specimen. Cytokeratin accentuated the ductal structures. S-100 showed a diffuse staining pattern, with darker staining of the spindled myoepithelial cells. The Her-2-neu protein showed moderate cytoplasmic staining, whereas the p53 showed only occasional labeling of nuclei. This is the first case of sialoblastoma with evidence of increasing anaplasia based on increasing proliferative capacity. Therefore, the distinction between benign and malignant sialoblastomas may not be as well defined as previously thought. The patient's prognosis is likely to be determined by the tumor grade as well as the stage at presentation and the extent of resection.

Biomarkers, Tumor↗
PubMed1999

The back door: venous-mediated metastasis into cervical lymph nodes as an alternative metastatic pathway for oropharyngeal squamous cell carcinoma.

Circulating lymphocytes may home to lymph nodes (LNs) via paracortical postcapillary venules, high-endothelial venules (HEVs) that recognize circulating lymphocytes, enabling them to migrate into nodal cortical/paracortical regions. Our goal was to find any histologic, immunohistochemical, or in vitro evidence to support the hypothesis that squamous cell carcinoma (SCC) may gain access to LNs via an alternative venolymphatic pathway. Slides from 67 neck dissections with SCC were studied. Standard criteria for lymphatic-mediated metastasis were used; criteria for evidence ofvenolymphatic metastasis were tumor nests localized to the paracortical regions, directly contiguous to HEVs but not marginal sinuses. Cases in which LN architecture was obliterated by metastases were excluded. A modified Stamper-Woodruff assay, which assesses HEV binding, incubated cell lines from oral carcinomas and lung adenocarcinomas with fresh frozen LN sections. Double-blinded cell counts were performed by two observers and analyzed by Student's t test. Immunohistochemical examination was undertaken on 19 paraffin-embedded cases with the monoclonal antibody, MoAb CD44v6, to discover whether expression of this adhesion molecule correlated with metastatic pattern. Twenty-nine cases (66%) revealed evidence only for the LN route of metastasis; 4 cases (9%) were classified as venolymphatic metastasis; 11 cases (25%) showed evidence for both pathways. The Stamper-Woodruff assay confirmed that SCC cells preferentially bound to HEV within cervical LN sections more than did adenocarcinoma cells (P = .02). Strong staining to MoAb CD44v6 was seen in 18 (95%) of 19 SCCs with a membranous pattern. Occasionally, CD44v6 highlighted tumor emboli adjacent to HEVs, but no overall correlation could be made between CD44v6 expression and pattern of spread. Tumor metastasis via lymphatic channels is the predominant mode of metastatic spread, but the venolymphatic route is a plausible alternative pathway. The preferential attachment of SCC cells to HEVs supports this theory.

Cell Adhesion↗
PubMed1998

Amplification of target-specific, ligation-dependent circular probe.

We describe a novel polymerase chain reaction (PCR)-based gene amplification method utilizing a circularizable oligodeoxyribonucleotide probe (C-probe). The C-probe contains two target complementary regions located at each terminus and an interposed generic PCR primer binding region. The hybridization of C-probe to a target brings two termini in direct apposition as the complementary regions of C-probe wind around the target to form a double helix. Subsequent ligation of the two termini results in a covalently linked C-probe that becomes 'locked on to' the target. The circular nature of the C-probe allows for the generation of a multimeric single-stranded DNA (ssDNA) via extension of the antisense primer by Taq DNA polymerase along the C-probe and displacement of downstream strand, analogous to 'rolling circle' replication of bacteriophage in vivo. This multimeric ssDNA then serves as a template for multiple sense primers to hybridize, extend, and displace downstream DNA, generating a large ramified (branching) DNA complex. Subsequent thermocycling denatures the dsDNA and initiates the next round of primer extension and ramification. This model results in significantly improved amplification kinetics (super-exponential) as compared to conventional PCR. Our results show that the C-probe was 1000 times more sensitive than the corresponding linear hemiprobes for detecting Epstein-Barr virus early RNA. The C-probe not only increases the power of amplification but also offers a means for decontaminating carryover amplicons. As the ligated C-probes possess no free termini, they are resistant to exonuclease digestion, whereas contaminated linear amplicons are susceptible to digestion. Treatment of the ligation reaction mixture with exonuclease prior to amplification eliminated the amplicon contaminant, which could also have been co-amplified with the same PCR primers; only the ligated C-probes were amplified. The combined advantages of the C-probe and thermocycling have a broad applicability for the detection of both DNA and RNA. Finally, we described a novel isothermal amplification method, ramification extension amplification, utilizing circular nature of C-probe and displacement activity of DNA polymerase.

Binding Sites↗
PubMed1998

Benign intratracheal thyroid: a possible cause for preoperative overstaging.

We report a rare case of intratracheal thyroid ectopia in the setting of papillary thyroid carcinoma, resulting in the preoperative clinical impression of an aggressive, high-stage tumor. A 24-year-old opera singer presented with complaints of a gagging or choking sensation. The results of computed tomography revealed a mass in the left thyroid lobe with multiple small calcifications consistent with papillary thyroid carcinoma as well as a soft tissue mass in the adjacent left tracheal lumen thought to be direct invasion by the thyroid tumor. A total thyroidectomy was performed including excision of half of the first and second tracheal cartilages and the lower portion of the hemicricoid cartilage. The final histological findings revealed that the intratracheal component was composed of benign thyroid tissue and strands of benign thyrocytes coursed through the first tracheal membrane. Intratracheal thyroid ectopia is a rare symptomatic occurrence with a striking female predisposition. We have identified 23 cases of intratracheal thyroid ectopia from the literature. They occur most often at the level of the cricoid, usually posteriorly with a slight predisposition for the left side. Continuity between the intratracheal component and the thyroid lobe may be seen. Clinicians and pathologists must be aware of this entity to avoid mistaking it for evidence of thyroid invasion by a malignant neoplasm.

Adult↗
PubMed1998

Clinical and molecular pathology of aggressive Schneiderian papilloma involving the temporal bone.

BACKGROUND: Inverting papilloma is a benign but locally aggressive sinonasal tumor that rarely involves the middle ear or temporal bone. METHODS: A report of a case and the molecular pathology of the tumor is presented. RESULTS: A 35-year-old woman with a history of recurrent inverting papilloma of the left paranasal sinuses was found to have evidence of extension through the eustachian tube and extensive involvement of the temporal bone. Surgical management resulted in the patient being disease-free at 14 months. Molecular pathology studies of the resected tumor suggest an association with human papillomavirus. CONCLUSIONS: Direct extension of the sinonasal tumor through the eustachian tube may represent the pathologic mechanism involved in the development of inverting papilloma involving the middle ear and temporal bone.

Adult↗
PubMed1997

Synchronous lingual granular cell tumor and squamous carcinoma. A case report and review of the literature.

Granular cell tumor (GCT) is a benign lesion with a preference for subcutaneous sites. Marked pseudoepitheliomatous hyperplasia, seen in 10% of GCTs, might be misdiagnosed as squamous cell carcinoma (SCC), and GCT in the oral tissues has been referred to as a medical curiosity in the literature. We report the clinicopathologic, immunohistochemical, and ultrastructural findings in a case of coexistent SCC and GCT in the tongue. There is no evidence in this case that suggests malignant transition of the GCT to carcinoma. To the best of our knowledge, this is the first report of synchronous GCT and SCC in the oral cavity.

Adult↗
PubMed1997

Adenosquamous carcinoma of the facial bones, skull base, and calvaria: CT and MR manifestations.

A 62-year-old woman had proptosis of the right eye, decreased visual acuity of the left eye, and no other focal neurologic deficits. She had a grand mal seizure 1 month before admission. The CT and MR studies showed extensive bone destruction of the margins of the right orbit, the floor of the middle cranial fossa, the right cavernous sinus, and much of the calvaria. There was considerable dural disease and tumor in the right orbit, paranasal sinuses, and scalp, as well as mucoceles of the left ethmoidal sinus with desiccated secretions. The diagnosis was adenosquamous carcinoma, an aggressive tumor related to both squamous cell carcinoma and adenocarcinoma.

Biopsy↗
PubMed1997

Sialoblastoma (embryoma): MR findings of a rare pediatric salivary gland tumor.

We report the findings in a 21-month-old girl who had a noninfiltrating mass in the left cheek, just anterior to the masseter muscle, which, at surgery, proved to be a sialoblastoma. Sialoblastoma has a histologic appearance reminiscent of a primitive state of salivary gland development; that is, it shows an arrested state of salivary maturation. MR imaging in this case showed that the lesion was isointense with muscle on T1-weighted images, had a high-intermediate signal intensity similar to that of fat on T2-weighted images, and enhanced sparsely and nonhomogeneously.

Adenoma↗
PubMed1996

Noninvasive and minimally invasive carcinoma ex mixed tumor: a clinicopathologic and ploidy study of 12 patients with major salivary tumors of low (or no?) malignant potential.

We studied 12 histologically malignant salivary tumors that showed complete encapsulation or only limited microscopic invasion. Most cases were histologically characterized by atypical and mitotically active luminal cells forming dilated, angular, variably sized glands in the subcapsular region, varying proportions of nonluminal tumor cells, and a background of central fibrosed hyalinized stroma. The appearance is that of a low-grade carcinoma. Focal higher grade carcinoma was superimposed on this histologic data in three cases. Neither recurrences nor metastases were seen in 11 of 12 patients after surgical resection with a follow-up of 1.2 to 13 yrs (mean, 4.2 years). Ploidy studies were performed on the paraffin-embedded tissue in 11 cases and yielded results for 7 cases. Aneuploid cell populations were found in five tumors; two had normal diploid populations; and the ploidy results are not predictive of tumor behavior. This type of salivary gland tumor fits diagnostically within the category of noninvasive and minimally invasive carcinoma ex pleomorphic adenoma (also referred to as in situ and low-grade malignant mixed tumors), a class that requires additional awareness and precise recognition as it signifies a good prognosis after surgical resection.

Adenoma, Pleomorphic↗
PubMed1996

Epstein-Barr virus reactivation in hairy leukoplakia.

Hairy leukoplakia, often seen in patients with acquired immunodeficiency syndrome, is strongly associated with Epstein-Barr virus (EBV) infection and questionably associated with human papillomavirus (HPV) infection. To date, most in situ hybridization (ISH) studies suggest that the EBV is localized only to the superficial squamous layers, favoring the theory of lingual infection by saliva rather than by reactivation of latent lingual infection. We describe 11 formalin-fixed, paraffin-embedded specimens from patients with lingual hairy leukoplakia that we examined for the presence of the EBV, HPV, cytomegalovirus, and human immunodeficiency virus. We used standard DNA ISH for the EBV and cytomegalovirus and polymerase chain reaction ISH for the EBV, HPV, and human immunodeficiency virus. The EBV was present in all 11 specimens according to polymerase chain reaction ISH studies but in only seven specimens according to conventional DNA ISH. Polymerase chain reaction ISH localized the EBV to the basal and parabasal layers in addition to the strong localization in the upper epithelial layers. No evidence for HPV or cytomegalovirus DNA was found. The human immunodeficiency virus was focally localized to rare superficial squamous cells in seven specimens. The presence of EBV DNA in basal and parabasal lingual cells, as well as localization of latency-associated proteins in these layers, suggests that hairy leukoplakia in patients with acquired immunodeficiency syndrome might represent a reactivation of latent lingual infection accompanied by a dramatic increase in viral copy number in the more mature, superficial, squamous cells. The human immunodeficiency virus was also found in seven specimens, but the significance of this new finding is uncertain and requires further study. There is no evidence to suggest that the HPV is involved in the development of hairy leukoplakia.

Herpesviridae Infections↗
PubMed1996

The role of imaging in the diagnosis of giant cell tumor of the skull base.

An expansile temporal bone lesion above the temporomandibular joint (TMJ) in a 55-year-old woman was initially diagnosed as pigmented villonodular tenosynovitis. Preoperative embolization of the tumor had resulted in excessive tumoral hemorrhagic pigment. The surgical and CT findings suggested that the TMJ was not involved, and a final diagnosis of giant cell tumor was made.

Diagnosis, Differential↗