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Biomedical subjects

G M Farrow

Publications and source records attributed to G M Farrow.

At least 37 records · Page 2Linked to original sources

Mesoblastic nephroma of adulthood. Report of three cases.

Mesoblastic nephroma is an uncommon congenital tumor of infancy that rarely occurs in adults. We report three patients (two were female, one was male) who had mesoblastic nephroma of adulthood and who presented at 45, 64, and 66 years of age with hematuria, flank mass, and pain. All underwent nephrectomy without postoperative adjuvant therapy. The tumors were solitary yellow-tan masses with solid and cystic areas involving the renal cortex (three cases) with extension into the renal pelvis and calyces (two) and ureter (one). Microscopically, all consisted of uniform spindle cell proliferations with entrapped dilated renal tubules. Focal necrosis was present in two, but no atypia or mitoses were identified in any case. The spindle cells displayed cytoplasmic immunoreactivity for vimentin, desmin, panmuscle actin (HHF-35), and alpha-smooth-muscle actin, but were nonreactive for keratin (AE1/AE3), epithelial membrane antigen, and S-100 protein. Electron microscopy revealed the presence of smooth-muscle differentiation in two cases and undifferentiated mesenchyme in one. All tumors were DNA diploid by flow cytometry. The patients were free of recurrence 8 months-2 years postoperatively. Because surgical excision may be curative, mesoblastic nephroma in adult patients must be differentiated from spindle cell neoplasms of the kidney that require additional therapy.

Aged↗

Human papillomavirus in penile squamous cell lesions. A comparison of an isotopic RNA and two commercial nonisotopic DNA in situ hybridization methods.

Sensitive isotopic in situ hybridization analysis of 34 paraffin-embedded penile squamous cell lesions for human papillomavirus (HPV) types 6, 11, 16, 18, and 31 revealed similar HPV detection rates, HPV-type specificity, and viral distribution patterns to those described in analogous cervical and vulvar lesions. Human papillomavirus was detected in six of six cases of condylomata acuminata (HPV type 6 [n = 4], HPV type 11 [n = 2]), in six of eight cases of squamous cell carcinoma in situ (HPV type 16 [n = 5], HPV type 31 [n = 1]), and in four of 10 cases of squamous cell carcinoma (all were HPV type 16). Interestingly, all 10 cases of penile verrucous carcinoma analyzed were HPV negative. Reevaluation of the HPV-positive penile lesions with two commercial nonisotopic HPV-typing in situ hybridization kits (Pathogene, Enzo, New York, NY; Viratype, Life Technologies, Gaithersburg, Md), revealed positive results for HPV type 6 and/or type 11 in all six cases of condylomata acuminata studied. However, only the Viratype assay detected HPV genome in the high-grade squamous cell lesions, with a relative sensitivity of 70% compared with that of the isotopic assay.

Carcinoma in Situ↗

Stage D1 prostate cancer treated by radical prostatectomy and adjuvant hormonal treatment. Evidence for favorable survival in patients with DNA diploid tumors.

BACKGROUND: Stage D1 disease is found in at least every sixth patient undergoing bilateral pelvic lymphadenectomy and radical retropubic prostatectomy (RRP) for clinically localized prostate cancer (PC). Previous recommendations for monotherapy using surgery, radiation, or systemic therapy alone for Stage D1 disease have usually been associated with a poor outcome in regard to progression and survival. Unlike other pathologic stages, D1 disease treated with RRP is mainly related to DNA ploidy pattern in regard to all end points (progression and survival) and immediate adjuvant hormonal treatment (AHT) rather than to the usual pathologic variables, including the number of positive nodes. METHODS: Complete DNA ploidy information was available in 370 patients with Stage D1 disease (age range, 40-77 years; mean, 64 years) undergoing RRP with or without AHT with a follow-up of up to 22 years (mean, 5 years). RESULTS: Overall, 80% of all DNA ploidy classes (diploid, 37%; tetraploid, 46%; and aneuploid, 17%) had AHT that highly significantly delayed progression for diploid (P less than 0.0001) more than tetraploid (P less than 0.0001) and more than aneuploid (P less than 0.0001) tumors. Significant prolongation of the disease-free interval might have improved the quality of life for tetraploid and aneuploid patients. Survival (crude and cause-specific) was significantly (P = 0.02) improved only for diploid patients who received AHT but not for tetraploid and aneuploid patients. This was due to the significantly accelerated death rate after progression in those patients with early AHT for tetraploid and aneuploid (but not diploid) tumors. Delayed (on progression only) AHT resulted in high progression rates for all DNA ploidy classes (aneuploid greater than tetraploid greater than diploid); e.g., 21 of 30 diploid patients progressed and 6 patients died from disease at a median of 31.5 months in spite of immediate hormone treatment on progression. RRP and AHT for patients with Stage D1 disease resulted in a highly significant delay in overall progression (76% at 10 years) and excellent local control, depending on DNA ploidy pattern (diploid greater than tetraploid greater than aneuploid) compared with a treatment regimen without AHT (24% overall nonprogression); only 20% of all patients with AHT are projected to die of disease at 10 years. Disease in diploid patients (37%) treated with AHT rarely progressed and those patients are unlikely to die of disease in 10 years or less; delayed (on progression) hormone treatment for diploid patients seemed ineffective. Inclusion of values for prostate specific antigen led to a higher failure rate on progression, and this is dependent on DNA ploidy class (diploid greater than tetraploid greater than aneuploid). CONCLUSION: Only patients with nondiploid tumors should be entered into prospective studies using innovative adjuvant treatment protocols to improve survival.

Adult↗

Cytogenetic analysis of six renal oncocytomas and a chromophobe cell renal carcinoma. Evidence that -Y, -1 may be a characteristic anomaly in renal oncocytomas.

Renal oncocytomas are benign tumors whose morphologic features may sometimes be confused with those of certain low-grade malignant neoplasms of the kidney, e.g., chromophobe cell and granular cell variants of renal carcinoma. The presence of a specific genetic abnormality might help differentiate these tumors. Because very few cytogenetic studies of renal oncocytomas have been published, we investigated a consecutive series of six such tumors. We also performed chromosome analysis on a chromophobe cell carcinoma because cytogenetic analyses of this tumor have not been previously reported. Tumor cell metaphases were analyzed after mechanical and enzyme disaggregation, in situ culture, and robotic harvesting. Clonal abnormalities were present in five of the six oncocytomas, and loss of chromosome 1 with loss of the Y chromosome occurred in two. Review of the literature disclosed four other renal oncocytomas with the 44,X,-Y,-1 karyotype. In the chromophobe cell carcinoma, we noted an abnormal clone with a del(11)(p12p15.1); similar anomalies were not observed in the renal oncocytomas. We conclude that renal oncocytomas have clonal chromosome abnormalities and that a subgroup of these tumors may be specifically associated with loss of chromosomes 1 and Y. Because this is a small series, further investigation may help establish whether cytogenetic studies can provide diagnostic and pathogenic information about renal oncocytomas.

Adenoma↗

The clinical significance of nuclear DNA ploidy pattern in 184 patients with pheochromocytoma.

Flow cytometric nuclear DNA analysis was performed on paraffin-embedded tissue samples taken from 184 patients with pheochromocytoma and paraganglioma treated between 1960 and 1987. The Hedley technique was used for measurement of nuclear DNA content. Thirty-five percent of the tumors were DNA diploid, 33% showed a DNA tetraploid pattern, and 32% had DNA aneuploid pattern. Familial pheochromocytoma and associated endocrine or neoplastic disorders were more common among patients with DNA nondiploid tumors. Eighty-four percent of the tumors that invaded blood vessels and all patients with regional or distant metastases had tumors classified as DNA tetraploid or DNA aneuploid. Of 22 patients who had disease progression, 21 (95%) had tumors with abnormal DNA ploidy pattern (P less than 0.001). All 12 patients who died of cancer-related disease had abnormal DNA ploidy; none of the patients with DNA diploid tumor (n = 64) have died of pheochromocytoma (P less than 0.01). These results suggest that nuclear DNA ploidy pattern is an important and independent prognostic variable for patients with pheochromocytoma and paraganglioma.

Adrenal Gland Neoplasms↗

Pathology of carcinoma in situ of the urinary bladder and related lesions.

In the United States, nearly all cases of bladder cancer are of the transitional cell type, and epidemiological evidence indicates that among these, approximately 80% present initially as more or less well-differentiated, superficial papillary neoplasms with a tendency for multifocal or diffuse involvement of the urothelial surface and/or recurrent tumor episodes, but with limited potential for invasive growth or a lethal outcome. Bladder tumors with lethal potential generally begin as poorly differentiated, sessile growths that are usually invasive at first diagnosis. Carcinoma in situ is a change that must be elicited among intact surface cells before progressive proliferation results in a tumor mass. Evidence for such an association is both temporal and spatial. Since most transitional cell carcinomas begin as well-differentiated tumors, i.e., resembling normal urothelium, recognition of early neoplastic alteration before a papillary structure forms is unlikely and most of the evidence is spatial based upon urothelial changes adjacent to papillary tumors. The morphologic definition of carcinoma in situ is arbitrary and generally defined as a total replacement of the urothelial surface by cells which bear morphologic features of carcinoma, but which lack architectural alteration other than an increase in the number of cell layers, i.e., a flat lesion. The Union Internationále Contra Cancer/American Joint Committee on Cancer (UICC/AJCC) staging scheme for bladder cancer distinguishes non-invasive papillary growths as Ta and carcinoma in situ as Tis. Because detection of carcinoma in situ, either by cytology or biopsy, depends upon recognizable malignant morphologic characteristics, studies of the lesion tend to be limited to the higher grade or more anaplastic examples.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗

Prognostic profile for patients with pheochromocytoma derived from clinical and pathological factors and DNA ploidy pattern.

Eighty-eight patients with pheochromocytoma and paraganglioma treated over a 28 year period (1960-1987) were studied. Based on clinical course, they were divided into three prognostic groups: benign (n = 57); multiple (n = 12); and metastatic (n = 19). Using clinical data, histopathologic findings, and tumor nuclear DNA content a prognostic profile for each group was constructed. The following variables were studied: age, familial pheochromocytoma, associated endocrine or neoplastic disorders, number and location of the lesion at diagnosis, size of the tumor, and the nuclear DNA ploidy pattern. Of these prognostic factors the most significant to predict a future malignant clinical course were large size and local tumor extension at time of surgery. Family history of pheochromocytoma, associated endocrine disorders, and young age at presentation predicted multiplicity. Old age, absence of familial pheochromocytoma or related endocrine disorders and DNA diploid tumors seem to be favorable findings. Using these variables in combination may be helpful for early identification of patients with malignant, multiple, or benign pheochromocytoma and paraganglioma.

Adrenal Gland Neoplasms↗

Nuclear deoxyribonucleic acid content measured by static cytometry: important prognostic association for patients with clinically localized prostate carcinoma treated by external beam radiotherapy.

To determine if relative nuclear deoxyribonucleic acid (DNA) content is an important prognostic parameter for patients with clinically localized prostate carcinoma treated by external beam radiotherapy, we performed static DNA cytometry on archival paraffin embedded prostate needle biopsy specimens obtained before treatment. DNA content was measured with the Zeiss IBAS 2000 Image Analyzer and the Feulgen staining method. Tumor samples from 65 patients with clinically localized carcinoma of the prostate treated with at least 6,000 cGy. from 1974 to 1980 were studied. Patients and tumors were divided into 2 groups: group 1 - 31 patients with relative DNA content less than 1.5 times normal and group 2 - 34 patients with relative DNA content greater than 1.5 times normal. The prostate cancer nonprogression rate at 10 years was 64% for group 1 and 11% for group 2. Prostate cancer cause specific survival at 10 years was 73% for group 1 and 20% for group 2. These differences are highly significant (p less than 0.0001). By contrast, stratification and analysis according to tumor clinical stage, Mayo histological nuclear grade or Gleason score proved not to be as significant. Cox multivariate analysis also identified DNA content as the most important independent variable for cancer specific survival and progression. Nuclear DNA content measured by static cytometry appears useful in identifying those patients with clinically localized prostate carcinoma who may have a favorable probability of long-term disease control by external beam radiotherapy.

Aged↗

Small cell anaplastic carcinoma of the prostate: a clinical, pathological and immunohistological study of 27 patients.

Because small cell anaplastic carcinoma of the prostate is an uncommon tumor, it has remained a poorly defined entity. To elucidate further the clinical, pathological and immunohistochemical characteristics of this cancer the 27 patients who presented to the Mayo Clinic from 1960 to 1990 were reviewed. Of these patients 18 (67%) presented with pure small cell anaplastic carcinoma, and 9 (33%) were diagnosed with small cell anaplastic carcinoma and adenocarcinoma of the prostate. Twenty-six patients (96%) had either stage C or D disease at the time of diagnosis. Two patients presented with a paraneoplastic syndrome, including 1 man with inappropriate antidiuretic hormone secretion and 1 who suffered from thyroxine intoxication. Of 24 men with long-term followup 22 (92%) died of small cell anaplastic carcinoma of the prostate despite antiandrogen therapy and the remaining 2 are alive with active, progressive disease. The median survival time following diagnosis was 17.1 months (range 2 to 90 months). All tumors with tissue available for immunohistochemical staining reacted positive for neuron-specific enolase, indicating that small cell anaplastic carcinoma of the prostate is most likely a neuroendocrine neoplasm. No tumor stained positive for either prostatic acid phosphatase or prostate specific antigen. Pathologically, small cell anaplastic carcinoma of the prostate appears to be similar to oat cell carcinoma of the lung. This series of 27 patients emphasizes that small cell anaplastic carcinoma of the prostate is highly malignant, is frequently of advanced stage at presentation, responds poorly to antiandrogen therapy and has a poor prognosis.

Adenocarcinoma↗

Idiopathic myelofibrosis with myeloid metaplasia involving the renal pelves, ureters and bladder.

Myeloid metaplasia associated with idiopathic myelofibrosis most commonly involves the reticuloendothelial organs, such as the spleen, liver and retroperitoneal lymph nodes. We report on a patient with myeloid metaplasia (extramedullary hematopoiesis) of the renal pelves, ureters and bladder. The pathogenesis, clinical characteristics, treatment and prognosis of this condition are discussed.

Adult↗

Penile verrucous carcinoma: a clinicopathologic, human papillomavirus typing and flow cytometric analysis.

The relationship of various verruciform squamous cell proliferations of the penis such as verrucous carcinoma, with or without anaplasia and giant condyloma, is uncertain. We conducted clinicopathologic, flow cytometric, and HPV typing studies on 15 cases of penile verrucous carcinoma to investigate its place in the spectrum of genital squamous proliferations. The results show a high degree of morphologic uniformity with respect to Ackerman's original diagnostic criteria, as well as to several other histopathologic features evaluated. The latter include polygonal squamous cells with glassy cytoplasm, centrally located vesicular nuclei, intercellular edema, well-formed cellular bridges, and absence or paucity of koilocytes, true fibrovascular cores, and keratohyalin granules. Intraepithelial abscesses and crust-formation were present in many cases. Four cases contained microscopic foci of cellular anaplasia. These hybrid verrucous-squamous carcinomas presented and behaved similarly to the pure verrucous carcinomas. Tumor recurrence was correlated with extent of initial surgical management. DNA ploidy analysis by flow cytometry performed on eight pure and two hybrid tumors showed uniform diploid populations with similar G1/G2 fractions in both groups. Eight pure and two hybrid tumors evaluated for HPV by isotopic in situ hybridization were uniformly negative for HPV types 6, 11, 16, 18, and 31. The results show that penile verrucous carcinoma demonstrates characteristic and uniform morphologic features and does not contain the HPV types typically associated with condyloma acuminatum, giant condyloma of Buschke-Löwenstein, and condylomatous carcinoma.

Adult↗

Renal cell carcinoma in young and old patients. Comparison of prognostic pathologic variables (cell type, tumor grade and stage, and DNA ploidy pattern) and their impact on disease outcome.

A group of 41 young patients (age less than or equal to 40 years; mean, 35.7 years) and a group of 34 old patients (age greater than or equal to 80 years; mean, 82.4 years) who underwent operation for renal cell carcinoma between 1970 and 1986 were compared. Sex, grade, and DNA ploidy pattern distributions were similar between the groups. Granular cell and papillary cancers with lower stages at presentation were more common among the young. In patients with high-stage disease, 73 percent of the older group but none of the younger had DNA diploid tumors. Low-stage clear cell carcinoma caused cancer death only in the young. Stage I nondiploid clear cell carcinomas were associated with death (33%) only in the young. Overall, death rates seem similar for both groups but among the young most (63%) occurred with low-stage disease and a nondiploid pattern only; among the old, 88 percent occurred with high-stage disease and independent of DNA ploidy pattern.

Adult↗

Non-germ cell tumors of testis.

Testicular tumors of non-germ cell origin represent from 5 percent to 10 percent of all testicular neoplasms. Included in this group are sex cord/gonadal stromal tumors, most originating from Leydig or Sertoli cells, mixed tumors, and tumors of mesenchymal or hematopoietic origin. In addition, various miscellaneous lesions, tumor-like conditions, and secondary testicular tumors may be classified as non-germ cell tumors. This review covers the presentation, diagnosis, and treatment of these rare lesions.

Humans↗

Adenocarcinoma of the prostate involving 2 cell types (prostate specific antigen producing and carcinoembryonic antigen producing) with selective metastatic spread.

Of 3 patients with clinically localized adenocarcinoma of the prostate 2 were treated by radical prostatectomy and 1 was treated with radiation therapy. Serum prostate specific antigen (PSA) values were elevated before therapy. After treatment the PSA levels were decreased to zero. All 3 patients later had evidence of metastatic tumor spread to the liver with elevation of serum carcinoembryonic antigen but not PSA. Immunohistochemical staining of the 2 primary tumors from the prostatectomy specimens identified 2 cell clones, one immunoreactive to PSA and prostatic acid phosphatase (PAP) and nonimmunoreactive to carcinoembryonic antigen, and the other immunoreactive to carcinoembryonic antigen but not PSA or PAP. Biopsy of a hepatic metastasis in 2 patients confirmed anaplastic carcinoma of the carcinoembryonic antigen-producing cell type. Immunohistochemical staining of a lymph node metastasis identified the PSA-producing cell type only. Such results suggest selective metastatic spread of each cell type to its own organ tropic site. Occasional carcinoembryonic antigen-producing prostate cancers may metastasize to the liver. Serum carcinoembryonic antigen measurements occasionally may be useful in the management of certain prostate adenocarcinoma patients.

Adenocarcinoma↗

Radical prostatectomy for stage A adenocarcinoma of the prostate: staging errors and their implications for treatment recommendations and disease outcome.

Of 148 patients with clinical stage A1 (32) or A2 (116) disease who had radical prostatectomy only 63% and 62%, respectively, had pathological stage A disease. Although 25% of those with clinical stage A1 and 9% of those with clinical stage A2 disease had no cancer at radical prostatectomy, 12% and 29%, respectively, had pathological stage C disease or higher. Clinical Mayo grade 1 was never associated with extracapsular disease but 60% of those with grade 3 or higher tumor did have extracapsular disease. Over-all survival was comparable to the expected survival. Clinical stage A2 cancer was associated with a significantly higher progression rate (when prostate specific antigen values were considered, p = 0.0011) and cancer death rate (p less than 0.045) than stage A1 disease, whereas pathological stage was not significantly related to disease outcome, possibly because of the use of adjuvant treatment (hormonal or radiation) for some patients with pathological stage C or higher disease. The vagaries of clinical staging associated with stage A disease, as well as the previously documented progression on long-term followup (8 to 10 years) in younger (60 years old or less) patients with stage A1 prostate cancer make radical prostatectomy with its limited morbidity an acceptable treatment choice.

Adenocarcinoma↗

The incidence of multicentricity in renal cell carcinoma.

We established the frequency of cancer multicentricity in kidneys removed for renal cell carcinoma by examining 100 intact, formalin preserved kidneys with a diameter of less than 80 mm. (1987 to 1989). The mean diameter of the predominant tumors was 51 mm. (range 15 to 80 mm). After the capsules were removed the kidneys were serially sectioned at 3 mm. intervals, and cortical and intraparenchymal nodules were removed for histological examination. A total of 3 kidneys had multiple tumors found previously on routine pathological examination. In addition, we discovered another 11 nodules in 10 other kidneys. Four nodules had histological features consistent with carcinoma. The size of the nodules ranged from 2 to 5 mm. The rest of the nodules consisted of 3 adenomas, 1 adrenal rest, 1 oncocytoma coexisting with an adenoma and 1 carcinoma permeating through the lymphatic vessels. The mean size of the predominant tumors in the kidneys bearing multiple nodules was 49 mm. Therefore, we observed a 13% incidence of small renal nodules and a 7% multicentricity of renal cell carcinoma in kidneys from patients who underwent nephrectomy.

Carcinoma, Renal Cell↗

Squamous cell carcinoma of the scrotum: long-term followup of 14 patients.

Squamous cell carcinoma of the scrotum was diagnosed in 14 patients from 1945 to 1990. Patient age at diagnosis ranged from 40 to 73 years, with the mean age of 62 years. The most common presentation was a solitary skin lesion but inguinal adenopathy was noted in 5 patients (36%). The mean delay to diagnosis for all patients was 22 months, with a range of 2 months to 10 years. Predisposing factors included psoriasis treated with coal tar or arsenic, human papillomavirus infection and multiple cutaneous epitheliomas. The primary lesion was treated by local or wide local excision in all 14 patients. In addition, 4 patients underwent inguinal lymphadenectomy and 3 underwent radiotherapy to the pelvic and inguinal lymph nodes. Mean followup for all patients was 6 years. However, 11 patients were disease-free with a mean followup of 7 years. Improved prognosis was noted in patients with locally confined disease or carcinoma in situ only. There was no correlation between grade of tumor and survival. All patients with stages A1 and B disease treated with wide local excision and/or inguinal lymphadenectomy have done well on followup. Radiotherapy does not appear to impact on survival for patients with high stage disease.

Adult↗