Lavinia P. Middleton

National Institutes of Health, Maryland, United States

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Publications (8)30.12 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Renal cell carcinoma (RCC) is the most common malignant tumor of the adult kidney, and its incidence has been steadily rising. RCC consists of several subtypes, each of which has its own clinical features, and cytogenetic and molecular characteristics. Recognizing histologic patterns of RCC is important not only for correct diagnosis, but also for providing insight into the biological behavior of the tumor and subsequent appropriate medical care for the patient. Pigments other than hemosiderin has been observed in RCC, but none of them have been proved to be melanin. Melanotic tumors, either primary or metastatic, are rare in the kidney. We present an unusual case of melanin-pigmented clear cell RCC with melanocytic differentiation, an unusual variant that may lead to errors in diagnosis and treatment.
    Human Pathlogy 03/2001; 32(2):233-6. DOI:10.1053/hupa.2001.22009 · 2.81 Impact Factor
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    ABSTRACT: Infiltrating pleomorphic lobular carcinoma (PLC) is an aggressive variant of infiltrating lobular carcinoma. Recently, in situ changes identical to PLC (PLCIS) have been described. The role of prognostic markers and their correlation with therapeutics, clinical outcome, and genetic changes is not well established in PLC. The authors examined 38 cases of this entity to understand better this tumor's biology. Immunohistochemical (IHC) analysis was performed in 21 specimens for estrogen and progesterone steroid receptors, p53, Her 2 (p185), and GCDFP-15. Genomic deoxyribonucleic acid was obtained from microdissected tumor as well as normal control cells, and loss of heterozygosity was investigated at the ESR (16q24), p53 (TP53 17p), Her 2 (17q 11-12), and BRCA 1 (17q12-25) loci. In this series, the average patient age was 57.5 years (age range, 24-92 years). Twenty-seven women were postmenopausal. Tumor size ranged from 1.2 to 25 cm. Six patients were a pathologic stage I; 19, stage II; 12, stage III; and one, stage IV. Histologically, multifocal nodular aggregates of discohesive pleomorphic tumor cells were seen interspersed in dense and fibrotic breast parenchyma. Twenty-nine percent of the specimens demonstrated associated signet ring cells. The remainder had dishesive, globoid, plasmacytoid cells with high-grade nuclear features. PLCIS was identified in 17 of 38 patients (45%), and lobular carcinoma in situ (LCIS) was noted in 8 patients (21%). IHC analysis showed estrogen immunoreactivity in 81%, progesterone in 67%, GCDFP-15 in 71%, and Her 2 in 81% (2+ to 3+ membranous staining) of specimens. Antibodies to p53 stained the tumor cell nuclei in 48% of the tumors. Loss of heterozygosity was identified in 52% of the specimens at the p53 locus, 18% at the ESR locus, 19% to 24% at the Her 2 loci, and 27% to 32% at the BRCA 1 locus. Follow-up was available in 19 patients and ranged from 12 months to 15 years (mean, 73 months). Seven patients had no evidence of disease at last examination (range, 1-15 years), three patients were alive with disease (range, 2-14 years), and nine patients were dead of disease (range, 2 months-9 years). Six patients had subsequent diagnoses of tumor in the contralateral breast. Analysis shows that PLC tends to appear in older postmenopausal women who present with locally advanced disease. PLCIS was found to be associated with PLC 45% of the time. The aggressive clinical course of patients with PLC is supported by tumor immunoreactivity with unfavorable markers Her 2 and p53. Overexpression of Her 2 in PLC may be therapeutically relevant, enabling the use of novel chemotherapeutic drugs like Herceptin. Interestingly, tumors that were Her 2 immunoreactive also maintained estrogen hormone immunoreactivity.
    American Journal of Surgical Pathology 01/2001; 24(12):1650-6. DOI:10.1097/00000478-200012000-00009 · 4.59 Impact Factor
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    ABSTRACT: Our objective was to determine the frequency of allelic loss at 8p21 in sporadic epithelial ovarian cancer. We recently described allelic loss at this locus in 7/9 ovarian cancers from patients with BRCA1 gene mutations. We anonymously obtained and examined 40 unselected invasive epithelial ovarian cancers and 5 low-malignant-potential (LMP) ovarian tumors for loss of heterozygosity (LOH) at 8p12-22. Pure epithelial and stromal cell populations were procured selectively by laser capture microdissection and extracted DNA was amplified with polymorphic microsatellite markers spanning the region of interest. LOH was highest (50%) at marker D8S136 located at 8p21 with 15 of 30 informative cases exhibiting an allelic deletion. None of the LMP tumors evaluated showed LOH at 8p12-22. A trend toward more frequent LOH at 8p12-22 was identified with increasing disease aggressiveness from LMP to early stage invasive ovarian cancer to advanced stage invasive ovarian cancer (Lehman's test, P2 < 0.024). Fifty percent allelic loss at the distal portion of 8p21 has not been reported to date for sporadic epithelial ovarian carcinomas. The higher rate of loss in our cohort, in contrast to previous allelotyping studies, is due likely to analysis from homogenous cell populations. These results, in concert with our previous study of BRCA1 mutation-positive patients, suggest a tumor suppressor gene locus at 8p21 for epithelial ovarian cancer.
    Gynecologic Oncology 08/1999; 74(1):98-102. DOI:10.1006/gyno.1999.5439 · 3.69 Impact Factor
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    ABSTRACT: Infiltrating micropapillary carcinoma of the breast is a recently described and poorly recognized aggressive variant of infiltrating ductal carcinoma for which the clinical significance and role of prognostic markers are not fully described. In 14 cases of infiltrating micropapillary carcinoma, we studied histologic characteristics; immunohistochemical expression of c-erbB-2, p53, and MIB-1; hormonal expression of these tumors; and genetic alterations on the p53 locus. We correlated these results with clinical outcome. Patient ages ranged from 37 to 58 years (mean, 50 yr). Nine patients presented with a palpable tumor, one with an axillary mass. Three patients had abnormal mammograms. Five patients (36%) presented with Stage II disease, eight (57%) with Stage III, and one (7%) with Stage IV. The tumors were a modified Bloom-Richardson Grade II in nine cases (64%) and Grade III in 5 (36%). Mitoses ranged from 1 to 12 per 10 high power fields. Necrosis was uniformly absent. Psammoma bodies were present in 9 cases (64%) and lymphatic invasion in 10 (71%). In all of the cases, c-erbB-2 was identified immunohistochemically, and MIB-I was positive, staining 30 to 60% of the tumor cells. The cells were immunoreactive for p53 in six (75%) of eight cases, and, when present, stained 20 to 50% of the tumor cells. Loss of heterozygosity on locus 17p13.1 (p53) was identified in 4 of 5 informative samples. Molecular and immunohistochemical analyses had an 80% concordance. Follow-up was available in 11 patients, of whom 9 had recurrence in the skin and chest wall (average time of recurrence, 24 mo). Recognition of this distinctive and aggressive variant of infiltrating carcinoma is important because of its unfavorable prognosis and specific pattern of local recurrence. Its aggressive nature is supported by its advanced stage at presentation and expression of unfavorable prognostic markers.
    Modern Pathology 06/1999; 12(5):499-504. · 6.36 Impact Factor
  • The Journal of Urology 01/1999; 162(5). DOI:10.1097/00005392-199904010-00786 · 3.75 Impact Factor
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    ABSTRACT: Adnexal tumours of probable Wolffian origin are rare low-grade malignant neoplasms that have been previously described in the broad ligament, ovaries and retroperitoneum of females. All are characterized by small, bland epithelial cells growing in a diffuse, trabecular, or tubular pattern. The majority of the cases reported have pursued a benign clinical course. However, recurrences and distant metastases have been described. We present a case of a male adnexal tumour of probable Wolffian origin occurring in the left seminal vesicle of a 29-year-old man with 23 years of follow-up. The diagnosis is supported by immunohistochemical and electron microscopic findings: The tumour cells were immunoreactive for cytokeratin and vimentin while smooth muscle antigen and S100 protein were uniformly negative. By electron microscopy cells were arranged in an acinar pattern and surrounded flocculent, electron-dense material. Individual cells contained numerous dense bodies and free ribrosomes. The patient had recurrences at 14 and 23 years after initial diagnosis. This is the first report of this entity in a male. The literature on this unusual tumour is reviewed and the clinicopathological, immunohistochemical and ultrastructural features are described. The differential diagnosis of this seemingly indolent tumour is discussed with genitourinary tumours having a more aggressive clinical course.
    Histopathology 10/1998; 33(3):269-74. DOI:10.1046/j.1365-2559.1998.00473.x · 3.30 Impact Factor
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    ABSTRACT: Epithelioid sarcomas are soft tissue tumors with an indolent, but potentially aggressive, clinical behavior. Distinction from other benign and malignant entities may be a diagnostic dilemma. In this study, we evaluate the presence of loss of heterozygosity (LOH) of chromosome 22q in tumor DNA from 13 epithelioid sarcomas, four epithelioid angiosarcomas, and two epithelioid hemangioendotheliomas, and investigate its possible role in diagnosis. LOH was detected in 6 of 10 (60%) of the informative epithelioid sarcomas. No allele loss was detected in the informative vascular tumors, three angiosarcomas, and two hemangioendotheliomas. Chromosome 22q carries the locus of a tumor suppressor gene, the neurofibromatosis 2 (NF2) gene, which has been shown to be lost or mutated in some NF2-related tumors, sporadic meningiomas, and vestibular schwannomas, as well as a few other tumors. Our data suggest that a region of chromosome 22q may be the locus of a tumor suppressor gene involved in the tumorigenesis of these neoplasms. Genetic alterations of yet-unknown tumor suppressor genes in this region, or even the NF2 tumor suppressor gene, may play a role in epithelioid sarcomas tumorigenesis. The fact that LOH was only detected in epithelioid sarcomas and not in the vascular tumors studied suggests a possible role for this marker in diagnosis.
    Human Pathlogy 07/1998; 29(6):604-8. DOI:10.1016/S0046-8177(98)80010-5 · 2.81 Impact Factor
  • Lavinia P. Middleton, Paul H. Duray, Maria J. Merino
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    ABSTRACT: Hemangiopericytoma (HPC) is an uncommon vascular neoplasm thought to be derived from pericytes. Prediction of patient outcome is difficult based what is currently known about these tumors and histological parameters alone. We compiled 27 cases of HPC and evaluated the spectrum of histological features to investigate whether there was any correlation between histology, immunostaining, prognostic markers, and patient outcome. The following parameters were evaluated: vasculature, histological pattern (solid, myxoid, trabecular, alveolar), degree of cellular pleomorphism, necrosis, mitoses, and giant cell content. Immunohistochemistry was performed to determine the reactivity for CD 31, CD34, vimentin, actin, cytokeratin, S100, actin, and SMA. Proliferative rate was analyzed using antibodies to PCNA and MIB1. Patient's age ranged from 8 months to 75 years (mean, 35; median, 31). Twenty of 27 cases were located in the extremities. The tumors were grossly described as lobulated and well circumscribed (n=12) and nonencapsulated (n=15). By histology, the characteristic ramifying or staghorn vasculature pattern was seen in all cases. A solid histological pattern was mixed with an alveolar pattern in three cases, trabecular pattern in six cases, and myxoid pattern in two cases. Tumor cells were uniform, polygonal to spindle-shaped, often with vesicular nuclei. Tumor giant cells were present in 9 of 27 cases; necrosis, in 11 of 27. Mitoses ranged from 0 to 14 per 10 high-power fields (HPF). Cellular pleomorphism was 1+ in nine cases, 2+ in 12 cases, and 3+ in six cases. Immunohistochemistry showed reactivity for CD34 and vimentin in all cases. Actin was focally positive in one case, and SMA was focally positive in another. CD 31, cytokeratin, and S100 were uniformly nonreactive. Proliferative index measured by PCNA and MIBI ranged between less than 1% and 40% of tumor cells. Follow-up was available in 22 cases and ranged from 1 year to 15 years. Seven patients had metastases, and two recurred locally. Thirteen patients had no evidence of disease at last checkup. Parameters associated with recurrences or metastases include a trabecular pattern, the presence of necrosis, mitoses, vascular invasion, and cellular pleomorphism. Features associated with an aggressive biological behavior can be identified histologically. There was some, but not total, correlation between proliferative markers and tumor aggressiveness.
    Human Pathlogy 07/1998; 29(6):636-40. DOI:10.1016/S0046-8177(98)80015-4 · 2.81 Impact Factor

Publication Stats

257 Citations
30.12 Total Impact Points


  • 1998–2001
    • National Institutes of Health
      • Laboratory of Pathology
      Maryland, United States
    • National Cancer Institute (USA)
      • Laboratory of Pathology
      Maryland, United States
    • University of Texas MD Anderson Cancer Center
      • Department of Pathology
      Houston, Texas, United States