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J Albores-Saavedra

Publications and source records attributed to J Albores-Saavedra.

At least 19 recordsLinked to original sources
PubMed1997

Role of O6-methylguanine-DNA methyltransferase in the resistance of pancreatic tumors to DNA alkylating agents.

Pancreatic adenocarcinomas rarely respond to radiation or chemotherapy, indicating that a large percentage of these tumors possess complex mechanisms of resistance. The failure of alkylating agents, such as carmustine [1,3-bis(2-chloroethyl)-1-nitrosourea; BCNU], lomustine [1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea; CCNU], and streptozotocin, to yield consistent therapeutic results further suggests that one of these mechanisms may be the high expression of O6-methylguanine-DNA methyltransferase (MGMT). All 12 human pancreatic ductal adenocarcinomas assayed for MGMT activity showed unusually high levels, implying that these malignancies are efficient in repairing genotoxic O6-alkylguanine lesions induced by methylating (streptozotocin) and 2-chloroethylating (BCNU and CCNU) chemotherapeutic genotoxic agents. Immunohistochemical analysis of an additional 15 pancreatic tumors showed that high levels of MGMT protein reside in the nucleus and the cytoplasm of malignant cells. Both nuclear and cytoplasmic staining were absent in hyperplastic duct epithelium, but staining was invariably present in moderate to highly dysplastic foci and especially strong in invasive components of the tumor. With the exception of lymphocytes that were MGMT positive, acinar, ductal, and islet cells did not stain for MGMT in histologically normal pancreata. These data indicate that MGMT activity is up-regulated in dysplastic epithelium, and its expression increases during tumor progression, reaching the highest levels in the invasive components of the tumor. Resistance of pancreatic tumor cells to alkylating agents was verified with four pancreatic tumor cell lines. CAPAN-2, CFPAC-1, PANC-1, and MIAPaCa-2, having MGMT levels of 1800, 987, 700, and 880 fmol/mg protein, respectively, were resistant to BCNU, but their resistance declined sharply following pretreatment with the MGMT inhibitor O6-benzylguanine (O6-BG). On the other hand, PANC-1 and MIAPaCa-2 could not be eradicated with N-methylnitrosourea (MNU) at concentrations as high as 2 mM, even when pretreated with O6-BG. These two lines were shown to be modified genetically in microsatellite sequences by MNU and are believed to have a defective mismatch repair system, which may explain their resistance to methylating agents. Failure of pancreatic tumors to respond to nitrosoureas is related to high levels of MGMT expression and in some cases to genomic instability. However, these tumors can be sensitized to chloroethylating drugs and eradicated following the elimination of MGMT activity by O6-BG or homologous MGMT inhibitors.

Adenocarcinoma↗
PubMed1997

Macrofollicular variant of papillary thyroid carcinoma with minor insular component.

BACKGROUND: The macrofollicular variant of papillary thyroid carcinoma that is the subject of this study has only recently been characterized. Information about its morphologic spectrum and biologic behavior is limited. METHODS: The authors reviewed 29 examples, including 17 previously reported cases. The clinical and pathologic features of five patients who had the macrofollicular variant of papillary thyroid carcinoma with a minor insular component were analyzed in detail. The insular component in thyroid carcinomas has been associated with aggressive clinical behavior. RESULTS: The ages of the 5 patients ranged from 31 to 70 years; the mean age was 40 years. Three patients presented with a palpable thyroid nodule and two with a large thyroid mass of long duration. The latter two tumors, which metastasized, were the largest (8 and 11 cm) and showed extrathyroidal and blood vessel invasion. All five tumors were composed predominantly of macrofollicles (>50%) and had a minor insular component that comprised less than 5% of the tumor mass. In most tumors, the macrofollicles were lined by cells with large, clear, grooved nuclei, and all five contained areas of conventional follicular variant of papillary thyroid carcinoma. In the two that metastasized, however, the lining of many macrofollicles consisted of cuboidal cells with small, hyperchromatic, follicular-type nuclei. Only the macrofollicular component was identified in the metastatic deposits in these two patients. All five patients were alive at last follow-up, two with metastases; but follow-up for this study is limited. CONCLUSIONS: A minor insular component is an additional feature of the macrofollicular variant of papillary thyroid carcinoma that may aid in diagnosis and does not appear to have an adverse effect on the excellent prognosis of patients with these tumors.

Adult↗
PubMed1997

Signet-ring sinus histiocytosis: a reactive disorder that mimics metastatic adenocarcinoma.

BACKGROUND: Signet-ring sinus histiocytosis is a rare and distinctive reactive disorder recently observed in the axillary lymph nodes of patients with breast carcinoma. This form of sinus histiocytosis closely resembles and can easily be confused with metastatic adenocarcinoma. METHODS: To determine the incidence of this reactive process in lymph nodes from different anatomic sites, broaden its morphologic spectrum, and discuss the differential diagnosis, the authors examined lymph nodes from 316 radical prostatectomy specimens, 184 modified radical mastectomy specimens, 108 colectomy specimens, 57 gastrectomy specimens, and 27 radical hysterectomy specimens. These surgical procedures were performed to treat carcinoma of the prostate, breast, colon, stomach, and uterine cervix, respectively. A total of 9741 lymph nodes were histologically examined. The lymph nodes containing sinus signet-ring cells were stained with mucicarmine, Alcian blue, and periodic acid-Schiff stains (PAS). Immunostains for epithelial, lymphoid, and histiocytic markers were also performed. In two cases, tissue was retrieved from the paraffin block and subsequently processed for electron microscopic examination. RESULTS: Only 4 of 316 radical prostatectomy specimens (1.2%) and 2 of 184 axillary dissections (1.08%) contained lymph nodes with signet-ring sinus histiocytosis. Of 9741 lymph nodes reviewed, 37 (24 pelvic and 13 axillary lymph nodes) had signet-ring sinus histiocytosis, for an incidence of 0.38%. Microscopically, the signet-ring histiocytes lacked nuclear atypia and were mucin negative. In two cases, clusters of histiocytes with rounded, eosinophilic, diastase resistant, PAS positive cytoplasmic globules were observed. Both types of signet-ring cells showed reactivity for histiocytic markers and were negative for cytokeratin and lymphoid markers. By electron microscopy, most histiocytes were shown to have a large empty vacuole that displaced the nucleus. Granular material was observed in some of the vacuoles. Some histiocytes exhibited a rounded cytoplasmic body composed of central electron dense, granular material and a rim of microfibrils. No lipid droplets were identified. CONCLUSIONS: Signet-ring sinus histiocytosis is a rare and distinctive reactive disorder found incidentally in the pelvic and axillary lymph nodes of patients with carcinoma of the prostate and breast, respectively. Although this histiocytic reaction mimics metastatic adenocarcinoma and signet-ring cell lymphoma, it can be identified by careful cytologic analysis together with positive reactivity for histiocytic markers, negative mucin stains, and lack of reactivity for epithelial and lymphoid markers. The etiology and pathogenesis of this unusual form of sinus histiocytosis remains unclear.

Adenocarcinoma↗
PubMed1997

Transitional cell carcinoma of the endometrium and endometrial carcinoma with transitional cell differentiation.

BACKGROUND: Transitional cell carcinoma (TCC) is rare in the female genital tract. Although it is most common in the ovary, small series of cases in the cervix have been reported, with isolated cases described in the fallopian tube, adnexa uteri, and endometrium. METHODS: Eight cases of primary TCC involving the endometrium and 1 case of ovarian TCC metastatic to the endometrium were retrieved from the files of the Armed Forces Institute of Pathology and the University of Texas Southwestern Medical Center. Cases were selected based on the presence of endometrial TCC, whether pure or combined with other patterns, and regardless of the relative amount. Immunostaining for cytokeratins 7 and 20 was performed. RESULTS: Among the 8 women with primary endometrial tumors, the mean age was 61.6 years (range, 41-83 years). Uterine bleeding was the presenting symptom in 7 women. Macroscopically, the tumors were polypoid, and infiltrated the myometrium, although the extent of infiltration varied. Seven endometrial tumors showed a papillary component. TCC was always admixed with other patterns (predominantly squamous, but also endometrioid, papillary, and serous patterns), with the proportion of the TCC component ranging from 5% to 95% (mean, 63.8%). TCC was the main invasive pattern observed in all three of the cases that had deep myometrial invasion; these cases also had vascular invasion. Seven tumors were confined to the uterus; one was metastatic to the ovary. The ovarian TCC metastatic to the endometrium had a pure TCC pattern. Five of 7 cases of TCC had cytokeratin 7+/20- immunoreactivity; 2 cases were cytokeratin 7-/20-. Treatment of primary endometrial tumors was mainly surgical, with adjuvant radiation therapy in 4 cases or chemotherapy in 1 case. Survival ranged from 3 months to 12.9 years (mean, 5.1 years). Of five women for whom follow-up was available, three were alive with no evidence of disease, one was alive with a local recurrence, and one died of unrelated disease. CONCLUSIONS: TCC is a rare, distinct subtype of endometrial carcinoma with morphologic features of urothelial differentiation, but retention of a mullerian immunoprofile. While the overall prognosis does not appear to be worse than what might be anticipated for the stage of tumor present, TCC appears to be the more aggressive histologic subtype among the patterns with which it is admixed.

Adult↗
PubMed1997

Atypical carcinoid of the esophagus: a case report and review of the literature.

BACKGROUND: Although carcinoid tumors of the gastrointestinal tract are relatively common, their occurrence in the esophagus is exceedingly rare. The authors report a case of an atypical carcinoid presenting in the cervical esophagus of an 82-year-old woman. METHODS: The tumor was studied with routine, silver, and immunohistochemical techniques for cytokeratin, chromogranin, and various secretory products. In addition, the literature was reviewed for carcinoid tumors of the esophagus and the findings summarized. RESULTS: The esophageal tumor showed focal necrosis, atypical cytologic features, and increased mitotic activity. It stained diffusely for chromogranin and focally for serotonin; thus it was considered an atypical carcinoid. The patient was free of disease 9 months after excision. On review of the literature, 13 additional cases of esophageal carcinoid were found. The average age of the patients was 60 years with a male predominance of 6:1; the most common presenting symptoms included dysphagia and weight loss. The majority of tumors occurred in the submucosa of the lower esophagus, and ranged in size from 1 to 12 cm. All patients except one had surgical treatment, three received adjuvant radiotherapy or chemotherapy. Although follow-up was limited, survival correlated with stage; seven of ten Stage I or II patients were disease free whereas three of four Stage III or IV patients had died of disease; the fourth patient is alive with brain metastases. CONCLUSIONS: Esophageal carcinoid tumors are exceedingly rare neoplasms. They usually occur in the lower esophagus of males who present with dysphagia. Survival statistics are limited, but appear best correlated with disease stage.

Aged↗
PubMed1997

Pigmented extraadrenal paragangliomas. A clinicopathologic and immunohistochemical study of five cases.

BACKGROUND: Pigmented extraadrenal paragangliomas are unusual neoplasms that have rarely been reported in the literature. METHODS: The clinical, pathologic, and immunohistochemical features of five cases of pigmented extraadrenal paragangliomas were reviewed. RESULTS: The patients were 2 women and 3 men within the ages of 17 and 56 years (mean age: 36.5). Two neoplasms were located in the lumbar spine, one in the urinary bladder, one in the anterior mediastinum, and one in the retroperitoneum. Clinically, one patient with spinal paraganglioma presented with symptoms of numbness and weakness of the lower extremities whereas the second patient had low back pain of several weeks' duration. The paraganglioma of the bladder occurred in a pregnant woman who had symptoms of dysuria and microscopic hematuria whereas the patient with an anterior mediastinal tumor presented with chest pain. No clinical history was obtained from the patient with the retroperitoneal tumor. None of the patients had a history of hypertension. Grossly, the tumors were described as well-circumscribed, soft, and slightly hemorrhagic, and measured from 2 to 9 cm in greatest dimension. Histologically, the five tumors displayed characteristics similar to those described in these tumors, mainly the presence of an organoid or zellballen growth pattern. In addition, they contained moderate amounts of intracellular melanin pigment that focally obscured the true nature of the lesion. Immunohistochemically, four cases were positive for chromogranin whereas S-100 protein was detected in the sustentacular cells in four cases. Follow-up information ranging from 6 months to 18 years for 3 patients revealed that the patients were alive and well without recurrence or metastasis. One patient with spinal paraganglioma was lost to follow-up, and the patient with mediastinal paraganglioma was a recent case and therefore the behavior of the paraganglioma could not be assessed. CONCLUSIONS: The current study expands the morphologic spectrum of extraadrenal paragangliomas and emphasizes the need to consider these tumors in the differential diagnosis of pigmented neoplasms. These findings suggest that the presence of melanin pigment does not alter the behavior of these neoplasms.

Adolescent↗
PubMed1997

K-ras mutations and allelic loss at 5q and 18q in the development of human pancreatic cancers.

CONCLUSION: Our findings have implications for early diagnosis and for the identification of patients at increased risk. BACKGROUND: Invasive cancers of the pancreas frequently are preceded by and associated with a spectrum of preneoplastic changes. We investigate the presence of K-ras mutations and allelic loss at 5q and 18q loci in preneoplastic lesions associated with nine cases of invasive pancreatic ductal carcinomas. METHODS: We precisely microdissected 115 foci of normal, preinvasive, and invasive foci from paraffin-embedded sections. RESULTS: 1. K-ras mutations occur early in the pathogenesis of pancreatic adenocarcinoma. Mutations were identified in multiple preneoplastic foci associated with al six cases in which ras mutations were present in the corresponding invasive cancers, including nearly all foci of mucous cell and atypical hyperplasia, in some cases of papillary hyperplasia (40%), and in one example of morphologically normal epithelium. 2. Ras mutations in preneoplastic foci are widespread, occur distant from the invasive tumor, and may present multiple mutations. Two, and in one case three, different types of K-ras mutations were found in separate preneoplastic foci from three individual cases. 3. Evidence for a "second hit" in the ras gene (i.e., loss of wild-type allele or amplification of the mutant allele) was present in some tumors and may be associated with the invasive process. 4. In contrast to ras mutations, limited data suggest that loss of heterozygosity (LOH) at 5q and 18q are relatively late events.

Alleles↗
PubMed1997

Pancreatic mucinous cystic neoplasm with sarcomatous stroma: a report of three cases.

Three patients with pancreatic mucinous cystic neoplasms having a sarcomatous stroma are reported. The tumors occurred in two women and one man, aged 48, 66, and 67 years, respectively. Symptoms included epigastric pain or a palpable abdominal mass or both. Radiographically, all the tumors were large, multicystic, and located in the tail of the pancreas. Histologically, the cystic component was lined by mucin-producing, columnar to cuboidal epithelium composed of benign to atypical to overtly malignant cells (cystadenocarcinoma). Immunohistochemistry showed the epithelial component of all three tumors to be positive with cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, and the pancreatic epithelial mucin antibodies CA 19-9 and DUPAN 2. In all three cases, an undifferentiated malignant spindle cell (sarcomatous) stroma was intimately associated with the epithelial component. The sarcomatous component showed variable reactivity with vimentin (all three cases), muscle-specific and smooth-muscle actin (all three cases), S-100 protein (1/3), Leu-7 (one case), and estrogen and progesterone receptors (in two cases). Two patients died with widespread abdominal disease within 15 months of diagnosis, one of whom had an omental metastasis entirely composed of the sarcomatous stroma. The third patient was alive and free of disease at 16 months after diagnosis. Our findings document the existence of a sarcomatous component in pancreatic mucinous cystic neoplasms; this component appears to be responsible for the highly malignant behavior of the tumors.

Aged↗
PubMed1997

Ectopic prostatic tissue in the uterine cervix.

This is the first reported case of ectopic prostatic tissue in the uterine cervix, diagnosed in a 38-year-old woman. A cluster of benign prostatic glands with cribriform and papillary patterns and focal squamous metaplasia occupied the superficial endocervical stroma. The glands were immunoreactive for prostatic specific antigen and prostatic specific acid phosphatase. This lesion, which could be confused with microglandular hyperplasia, mesonephric rests, or adenocarcinoma in situ may represent an embryonic rest.

Acid Phosphatase↗
PubMed1996

Low grade salivary duct carcinoma. A distinctive variant with a low grade histology and a predominant intraductal growth pattern.

BACKGROUND: Salivary duct carcinoma (SDC) has been established as a morphologically distinct and highly aggressive (HG) malignancy of the major salivary glands. However, a low grade (LG) or intermediate grade salivary duct neoplasm has not been described. METHODS: We report the clinicopathologic findings of 10 cases believed to represent the (LG) counterpart of SDC. Immunoperoxidase stains were performed on five cases, and electron microscopy on three. RESULTS: All of the tumors occurred in adult patients with no sex predilection, and presented as slow growing parotid gland lesions. Four cases involved the superficial lobe, one the deep lobe, and one arose within an intraparotid lymph node. The exact location of the tumor within the parotid gland was not stated in four cases. The size of the tumors ranged from 0.7 to 4 cm in greatest dimension, with most measuring between 1 and 2 cm. The gross appearance was focally to predominantly cystic. Microscopically, the tumors were characterized by intraductal proliferative lesions exhibiting three main patterns: (1) cystic ducts with micropapillary, tufted, and plaque-like intraluminal projections; (2) ducts distended by a solid or pseudocribriform (fenestrated) cellular proliferation, with varied cystic dilatation; and (3) ducts exhibiting architectural atypia. The three patterns coexisted and merged in most tumors, in varying proportions. All tumors shared bland to LG cytologic features, with the exception of one that had focal high-grade cytologic ductal atypia. Despite gross circumscription, there was microscopic multifocality, and in one case, stromal invasion. By immunohistochemistry, the neoplastic cells expressed the conventional ductal and glandular epithelial cell markers in addition to strong positivity for S-100 with coexpression for CK-903. Electron microscopy confirmed the ductal phenotype of the tumors and supported an in situ process evidenced by the presence of native myoepithelial cells. Nine patients underwent total parotidectomy and one superficial parotidectomy. One patient received radiation therapy following total parotidectomy. Follow-up for 6 cases ranged from 2 to 12 years and revealed no evidence of disease. CONCLUSIONS: LG-SDC represents the LG end of the spectrum of salivary duct malignant neoplasms and exhibits differentiation towards an intercalated duct-like cell phenotype. Its relationship to HG-SDC should be further explored.

Adult↗
PubMed1996

Physiologic versus neoplastic C-cell hyperplasia of the thyroid: separation of distinct histologic and biologic entities.

BACKGROUND: Although hyperplasia of C-cells has been described in association with various pathologic and physiologic conditions, criteria for its diagnosis are poorly defined. Both neoplastic and physiologic C-cell proliferations have been lumped together under the umbrella designation of C-cell hyperplasia (CCH), creating considerable confusion among clinicians and pathologists. METHODS: in order to compare the morphologic and immunohistochemical characteristics of the two major types of CCH, we examined thyroid sections of 17 patients with familial forms of C-cell hyperplasia and/or neoplasia and tissue sections of 19 thyroid glands known to have reactive or physiologic CCH (at least 50 C-cells per one low power field, 100X). Hematoxylin and eosin (H & E) stained sections and immunohistochemical stains for calcitonin were assessed in each case. RESULTS: Physiologic or reactive CCH was not recognized with certainty on H & E stains in any of the cases due to morphologic similarities between C-cells and adjacent follicular cells. Detection of this form of hyperplasia, which was predominantly diffuse, required calcitonin immunostains and quantitative analysis. Conversely, nodular and diffuse neoplastic CCH was easily identified with conventional H & E stains at the periphery of 11/12 (92%) familial medullary thyroid carcinomas (MTC). In the other five cases, neoplastic C-cell hyperplasia was the only pathologic finding on thyroidectomy performed for elevated serum calcitonin levels detected via provocative biochemical screening or identification of the mutated RET proto-oncogene by genetic analysis. The C-cells in this neoplastic form of CCH were large, mildly to moderately atypical, and confined within the basement membrane of thyroid follicles. Moreover, these cells were cytologically indistinguishable from those of invasive MTC cells. CONCLUSIONS: Physiologic and neoplastic CCH are biologically and morphologically distinct entities. The former cannot be recognized with certainty with conventional stains and requires immunohistochemistry and quantitative analysis for diagnosis. The latter consists of mildly to moderately atypical C-cells that can be identified with H & E stained sections. Consequently, the number of C-cells is of no importance for the diagnosis of neoplastic CCH which is considered to be the precursor (medullary carcinoma in situ) of invasive medullary carcinoma.

Adolescent↗
PubMed1996

p53 protein overexpression in gallbladder carcinoma and its precursor lesions: an immunohistochemical study.

Gallbladder carcinoma is one of the most frequent neoplasms diagnosed in Chile. Although the premalignant lesions have been extensively studied and are well characterized, there is only limited information about the genetic abnormalities that might be important in the pathogenesis of gallbladder carcinoma or that might have prognostic implications. The present study evaluates the immunohistochemical expression of p53 protein in premalignant lesions and invasive carcinoma of the gallbladder, and correlates the p53 expression with histological type, grade of differentiation, and level of invasion of the tumor. The authors studied the immunohistochemical p53 protein overexpression in 52 gallbladder carcinomas, 47 carcinomas in situ (CISs), 34 dysplasias, and 10 specimens with chronic cholecystitis containing normal and metaplastic epithelium. A semiquantitative scoring system was used to assess the p53 reactivity. p53 overexpression was found in 34 of 52 (65.4%) carcinomas, 21 of 47 (44.7%) CISs, and 11 of 34 (32.4%) dysplasias. There were no significant differences in p53 expression in premalignant lesions associated with invasive carcinoma and those that were not. Normal and metaplastic epithelium did not overexpress p53 protein. In adenocarcinomas, no correlation was found between p53 protein overexpression and histological subtype, grade of differentiation, or level of invasion. The high incidence of p53 overexpression in gallbladder carcinoma and its presence in dysplasia, even in specimens without invasive carcinomas, suggests that this abnormality is an important and early event in the pathogenesis of the tumor. The progressively increasing incidence of p53 overexpression observed from premalignant lesions to invasive tumor provides additional support to the view that this is the usual route for the development of infiltrating gallbladder carcinoma.

Carcinoma↗
PubMed1996

Loss of heterozygosity and microsatellite alterations in p53 and RB genes in adenoid cystic carcinoma of the salivary glands.

Adenoid cystic carcinomas (ACC) constitute approximately 20% of malignant salivary gland tumors. Several histological types of ACC are recognized and may coexist in a single tumor. The authors divided ACC into lower grade (tubular and cribriform subtypes) and higher grade (trabecular and solid) subtypes. A preliminary analysis of 10 ACCs showed a relatively high incidence of loss of heterozygosity (LOH) at the p53 and RB genes and low or absent K-ras mutations and LOH at chromosomal loci 3p, 5q, 8p, and 9p. From 21 tumors, the authors carefully microdissected and analyzed 36 subtype foci. Three interrelated pieces of evidence indicate that the relatively poor prognosis higher grade subtype arises from one or more of the lower grade subtypes via progression events associated with mutations in the p53 or RB genes. First, the number of mutations (both LOH and microsatellite alterations) at either gene is greater in higher grade foci than in lower grade foci; second, multiple mutations (two and occasionally three) are present in only higher grade foci; and third, when lower and higher grade foci are present in the same tumors, identical mutations plus other mutations are present in the corresponding higher grade foci. These findings suggest that molecular analyses of ACCs may provide information of prognostic importance.

Carcinoma, Adenoid Cystic↗
PubMed1996

Anaplastic variant of spermatocytic seminoma.

Four examples of spermatocytic seminoma with a predominant anaplastic component occurred in men 33 to 43 years of age, without histories of cyptorchidism. The seminomas presented with painless testicular masses recognized 3 to 18 months before orchiectomy. Preoperative serum measurements of human chorionic gonadotropin and alpha-fetoprotein were negative. All tumors contained areas (10% to 30% of the tumor) in which the three cell types characteristic of conventional spermatocytic seminoma could be identified under light microscopy. The predominant anaplastic component also contained the three cell types, but the nuclei had prominent nucleoli with granular and filamentous chromatin. In addition, sheets of cells with vesicular nuclei and prominent nucleoli superficially resembling embryonal carcinoma were found. There were numerous large mononuclear and multinucleated giant cells with bizarre nuclei and prominent nucleoli, but no sarcomatous elements. Many normal and abnormal mitotic figures were present. Tunical and vascular invasion and extensive necrosis were constant features. Immunohistochemistry documented p53 protein overexpression in two tumors, but neoplastic cells were negative with immunostains for placenta-like alkaline phosphatase, leukocyte common antigen, neuron-specific enolase, alpha-fetoprotein, human chorionic gonadotropin, vimentin, and cytokeratins. Ultrastructural examination of the anaplastic component showed large rope-like nucleoli, but the cytoplasmic features were similar to those of conventional spermatocytic seminoma. Despite the presence of a major anaplastic component, no patient has developed metastasis. Larger series and longer follow-up are needed to understand the natural history of these neoplasms.

Adult↗
PubMed1996

Mutations associated with carcinomas arising from pleomorphic adenomas of the salivary glands.

Pleomorphic adenoma (PA) is the most common benign tumor of salivary glands. Carcinomas in pleomorphic adenomas (CPAs) may arise by malignant transformation of the epithelial components of PAs. Occasionally, transitional zones containing cells with histological features intermediate between those of the benign PA and carcinomatous components of CPA are identified. After careful microdissection of archival microslides, the authors studied 12 cases of CPAs and their attendant adenomatous and transitional areas for mutations in the p53, RB, and K-ras genes, and at chromosomal loci 5q and 9p. The authors failed to find mutations in the K-ras gene or 9p locus. A relatively high rate of mutations (loss of heterozygosity [LOH] and microsatellite alterations) at the p53 gene were detected in CPAs (58%), and at somewhat lower frequencies at the RB gene (33%) and chromosomal location 5q (17%). Mutational frequency in the associated transitional and adenomatous areas were slightly lower than in the corresponding CPAs. No mutations were detected in adenomatous or transitional areas unless they also were present in the corresponding CPAs. Mutations of these three genes were absent in four cases of CPA, and in seven PAs without malignant change. These findings indicate that most CPAs arise from adenomas as the result of mutations in the three genes, especially p53. In addition, other, as yet unidentified genes may also be involved both in the development of PA and in its malignant progression to CPA. Mutational analysis of PAs may provide information of prognostic importance.

Adenocarcinoma↗
PubMed1996

High yields of K-ras mutations in intraductal papillary mucinous tumors and invasive adenocarcinomas induced by N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine in the pancreas of female Syrian hamsters.

Ductal adenocarcinoma, the most common form of pancreatic cancer in humans, is associated with activation of the K-ras oncogene in approximately 90% of cases. In contrast, K-ras mutations are found in < 50% of the relatively rare intraductal papillary mucinous tumor (IPMT), which arises in the main pancreatic ducts. Since both adenocarcinomas and IPMTs are believed to arise from ductal cells and progress through similar sequences of morphological changes (i.e. flat hyperplasia, papillary hyperplasia, atypia and carcinoma in situ), it is clear that such progression may not always necessitate activation of the ras oncogene. Experimentally ductal adenocarcinomas of the pancreas can be induced in the hamster model by a brief treatment with N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP), while IPMTs can be induced by a combined treatment with HPOP and orotic acid (OA) in an initiation/promotion schedule. Since animals are exposed to the carcinogen only once, initiated normal epithelium is expected to give rise to a wide spectrum of neoplastic and preneoplastic lesions, progression of which will depend on the extent of mutagenesis induced at initiation in the targeted cells. In order to investigate the role of K-ras in progression of IPMTs as compared with adenocarcinomas we have examined the presence of K-ras mutations in the above two types of experimentally induced pancreatic cancers, as well as in associated and preneoplastic lesions. K-ras mutations at codons 12, 13 and 61 were determined by a designed restriction fragment length polymorphism method using mismatched nested primers in 77 neoplastic and preneoplastic foci microdissected from 20 pancreases. Mutations were found in all foci of atypical hyperplasia, in carcinomas in situ and invasive cancer, whether such lesions originated in lobular tissue or in the main pancreatic duct. Mutations were also found in papillary hyperplasia and flat hyperplasia in small ducts and also in the main duct at high frequency. With one exception, all ras mutations were G-->A transitions at the second base of codon 12. Mutations were occasionally accompanied by excessive presence of the mutant ras allele or loss of the wild-type ras allele, events that were more frequent in atypical hyperplasia (5/17), carcinomas in situ (5/14), IPMTs (2/5) and invasive adenocarcinomas (2/5) than in flat hyperplasia (0/6) or papillary hyperplasia (2/18). Our results demonstrate that: (i) K-ras mutations, predominantly G-->A transitions, are present in all experimentally induced hamster tumors; (ii) the incidence of K-ras mutations in IPMTs is lower in humans than in the hamster model; (iii) advanced lesions in both adenocarcinomas and IPMTs were frequently associated with an excess of the mutant over the wild-type K-ras allele. It is likely that both adenocarcinomas and IPMTs induced chemically in the hamster model arise by mechanisms which involve early activation of K-ras. Such a mechanism seems to be applicable only in a fraction of human IPMTs.

Adenocarcinoma, Mucinous↗
PubMed1996

Carcinosarcoma arising in eccrine spiradenoma of the breast. Report of a case and review of the literature.

Although the vast majority of eccrine spiradenomas behave in a benign fashion, 23 cases of malignant transformation have been reported to date. We describe a unique example of malignant eccrine spiradenoma that arose in the right breast of a 68-year-old woman. The quiescent mass, which was present for approximately 50 years, experienced sudden enlargement with erythematous changes of the overlying skin and nipple discharge. Microscopically, the tumor showed the typical features of an eccrine spiradenoma with areas of adenocarcinoma, squamous cell carcinoma, and sarcoma. The sarcomatous component consisted of rhabdomyosarcoma and osteosarcoma. The immunoperoxidase staining revealed p53 protein expression only in the carcinomatous and sarcomatous components. This suggests that accumulation of p53 protein may be an important event in the malignant transformation of spiradenomas. Because of its location and biphasic nature, this malignant eccrine spiradenoma should be distinguished from metaplastic breast carcinoma. To our knowledge, this represents the first carcinosarcomatous transformation of eccrine spiradenoma in the breast. This case led us to conclude that breast tissue, which often undergoes apocrine metaplasia and gives rise to apocrine neoplasms, is also capable of originating benign and malignant tumors with eccrine sweat duct phenotype.

Adenocarcinoma↗