RESUMO
We report here the identification of a gene associated with the hyperparathyroidism-jaw tumor (HPT-JT) syndrome. A single locus associated with HPT-JT (HRPT2) was previously mapped to chromosomal region 1q25-q32. We refined this region to a critical interval of 12 cM by genotyping in 26 affected kindreds. Using a positional candidate approach, we identified thirteen different heterozygous, germline, inactivating mutations in a single gene in fourteen families with HPT-JT. The proposed role of HRPT2 as a tumor suppressor was supported by mutation screening in 48 parathyroid adenomas with cystic features, which identified three somatic inactivating mutations, all located in exon 1. None of these mutations were detected in normal controls, and all were predicted to cause deficient or impaired protein function. HRPT2 is a ubiquitously expressed, evolutionarily conserved gene encoding a predicted protein of 531 amino acids, for which we propose the name parafibromin. Our findings suggest that HRPT2 is a tumor-suppressor gene, the inactivation of which is directly involved in predisposition to HPT-JT and in development of some sporadic parathyroid tumors.
Assuntos
Adenoma/genética , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Hiperparatireoidismo/genética , Neoplasias das Paratireoides/genética , Proteínas/genética , Adenoma/patologia , Sequência de Aminoácidos , Sequência de Bases , Cromossomos Humanos Par 1 , Éxons , Etiquetas de Sequências Expressas , Genes Supressores de Tumor , Ligação Genética , Testes Genéticos , Genótipo , Heterozigoto , Humanos , Repetições de Microssatélites , Dados de Sequência Molecular , Fases de Leitura Aberta , Neoplasias das Paratireoides/química , Neoplasias das Paratireoides/patologia , Linhagem , Proteínas/química , Síndrome , Proteínas Supressoras de TumorRESUMO
The finding of possibly contaminant tissues or cells in surgical or cytology case material can be a challenging problem in diagnostic anatomical pathology samples. The reported rates of occurrence have ranged from 0 to 8.8% (including prospective and retrospective cases). A diagnostically dissimilar tissue fragment, whether contiguous with other tissue or among other fragments within a paraffin section, and which is not incompatible with the case tissue, often requires a rigorous investigation to confirm or deny its relevance to the case. Fluorescence in situ hybridization using dual red and green DNA probes to regions of the X and Y chromosomes, respectively, were used in one case where the potential contaminant was suspected to have originated from a male patient. The putative contaminant tissue fragment was confirmed as male, with cells having one X and one Y chromosome, unlike the other tissue fragments on the slide with two X chromosomes. In a second case, DNA polymorphisms were used to compare allelic patterns that were informative not only in proving the extraneous tissue as a contaminant, but in addition, could be used to trace the latter to its original tissue source. The molecular tools of fluorescence in situ hybridization in sex-mismatched cases and of DNA microsatellite probes that are applicable to paraffin sections can provide definitive identifiers of tissues and individual cells. They are important adjuncts to histology for the anatomical pathologist when faced with the diagnostic problems of tissue contamination encountered in routine practice.
Assuntos
Artefatos , Patologia Clínica/métodos , Controle de Qualidade , Idoso , Biópsia , Gastroscopia , Humanos , Hibridização in Situ Fluorescente , Masculino , Repetições de Microssatélites , Sondas de Oligonucleotídeos , Próstata/cirurgiaRESUMO
Invasive squamous cell carcinoma (SCC) in the upper aerodigestive tract (UADT) is usually preceded by severe keratinizing dysplasia, a manifestation of intraepithelial neoplasia. Despite the presence of surface maturation (keratosis), severe keratinizing dysplasia has a higher frequency of progression to SCC than full-thickness classic carcinoma in situ (CIS) as defined in the gynecologic tract. For this reason, we recommend that severe UADT dysplasia be combined with CIS under the rubric of "squamous intraepithelial neoplasia (SIN) grade III" to convey to the clinician the prognostic importance of these two diagnoses. Microinvasive carcinoma in the UADT includes a microfocus of submucosal invasion within 1-2 mm of the overlying epithelial basal lamina that is completely surrounded by nonneoplastic tissue. This conservative definition of microinvasion has a low risk, or no risk, for regional metastatic spread. Immunohistologic demonstration of basal lamina components is often absent in severe intraepithelial neoplasia (SIN III). Paradoxically, basal lamina is often observed in invasive SCC, especially neoplasms forming large cohesive aggregates and cords of invasive tumor. This finding negates the usefulness of basal lamina to identify microinvasive carcinoma, but its presence does appear to correlate with a low rate of progression of SCC invading with large cohesive tumor cords.
Assuntos
Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Laríngeas/patologia , Neoplasias Bucais/patologia , Membrana Basal/patologia , Humanos , Hiperplasia , Mucosa Laríngea/patologia , Leucoplasia Oral/patologia , Mucosa Bucal/patologia , Invasividade Neoplásica , Estadiamento de NeoplasiasRESUMO
This report is the second documented case of an adenomyoepithelioma arising in the breast. The neoplasm was well circumscribed and possessed cytologic features suggestive of a low-grade cancer; however, its biologic behavior remains undefined. The epithelial and myoepithelial elements are characterized ultrastructurally, and both are active participants in the neoplastic process. There are some histologic similarities of this lesion to the salivary gland epithelial-myoepithelial carcinoma; however, the growth pattern of cellular interductal proliferation of myoepithelium is unique.
Assuntos
Neoplasias da Mama/ultraestrutura , Carcinoma Adenoide Cístico/ultraestrutura , Epitélio/ultraestrutura , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
The histogenetic origin of the spindle-cell component of spindle-cell carcinoma of the head and neck mucosa remains controversial. The spindle cells have been considered a variant growth pattern of squamous-cell carcinoma, a non-neoplastic mesenchymal reaction, and a malignant admixture of epithelial and mesenchymal neoplasm. To evaluate the spindle-cell component, we studied 25 tumors (18 biphasic and seven monophasic) by utilizing the following: an avidin-biotin complex immunoperoxidase technique with a variety of antikeratin antibodies (AE1, AE3, CAM 5.2, 35BH11, and polyclonal Dako) and a monoclonal antivimentin antibody, and an avidin-biotin alkaline phosphatase double-labeling technique to detect coexpression of keratin and vimentin. The immunohistologic staining pattern was compared with electron-microscopic studies. Eight of 18 biphasic neoplasms contained immunoreactive keratin in the spindle-cell component that was distributed focally in a minority of cells in 3 tumors and diffusely throughout five of the neoplasms. Four of seven ulcerated monophasic spindle-cell tumors devoid of histologic squamous-cell carcinoma also were keratin positive, confirming epithelial differentiation. The majority of the spindle cells in all the tumors contained vimentin intermediate filaments. In three immunoperoxidase keratin positive biphasic tumors examined with alkaline phosphatase double labeling, occasional spindle cells were found that coexpressed keratin and vimentin and were interspersed with cells expressing either intermediate filament. Electron microscopy was performed on the spindle-cell component of 13 tumors, nine biphasic and four monophasic. Of the biphasic tumors, four were immunoperoxidase keratin positive; three of these showed epithelial differentiation by electron microscopy. Five biphasic tumors were keratin negative, and three tumors had epithelial differentiation by electron microscopy. Four monophasic spindle-cell tumors were immunoperoxidase keratin positive, and one of these had epithelial features by electron microscopy. Two monophasic tumors were keratin negative and without ultrastructural evidence of epithelial features. By using a combination of immunohistochemical and electron-microscopic observations, we identified evidence for epithelial differentiation in the spindled cells in 11 of 18 biphasic tumors and four of seven monophasic spindle-cell tumors.
Assuntos
Carcinoma de Células Escamosas/ultraestrutura , Carcinoma/ultraestrutura , Neoplasias de Cabeça e Pescoço/ultraestrutura , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais , Carcinoma/análise , Carcinoma/imunologia , Carcinoma de Células Escamosas/análise , Carcinoma de Células Escamosas/imunologia , Feminino , Neoplasias de Cabeça e Pescoço/análise , Neoplasias de Cabeça e Pescoço/imunologia , Humanos , Técnicas Imunoenzimáticas , Queratinas/análise , Queratinas/imunologia , Neoplasias Laríngeas/análise , Neoplasias Laríngeas/imunologia , Neoplasias Laríngeas/ultraestrutura , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Mucosa/análise , Mucosa/imunologia , Mucosa/ultraestrutura , Vimentina/análiseRESUMO
Epitheliosis is a benign intraluminal proliferation in the breast ducts and lobules that needs to be distinguished from ductal carcinoma in situ (DCIS). The histogenesis and differentiation of cells comprising epitheliosis have been the subject of some controversy. We evaluated the expression of a high-molecular-weight keratin (34 beta E12), muscle-specific actin (HHF-35), and S-100 protein immunoreactivity in formalin-fixed sections of the breast with epitheliosis and DCIS. In 28 of 30 cases of epitheliosis, there was strong HMW keratin immunoreactivity in the streaming sheetlike intraluminal proliferations. In contrast, 35 of 40 cases of DCIS (nonpapillary and papillary) were nonreactive for HMW keratin; the other five were weakly reactive. Furthermore, in 10 cases of DCIS, some ducts had isolated or small aggregates of HMW keratin-positive benign cells on the luminal aspects of the neoplastic proliferation that were reminiscent of a pagetoid pattern. Muscle actin-stained sections were analyzed to assess myoepithelial (ME) cell participation in epitheliosis. Muscle actin-positive ME cells were present at the periphery of the involved ducts but were absent or rare within epitheliosis. The distribution of ME cells--i.e., at the periphery of the spaces involved--was similar in DCIS and epitheliosis. S-100 protein was weakly but relatively consistently expressed by epitheliosis, but all cases of DCIS were negative. Six cases of atypical ductal hyperplasia included in the study were negative for HMW keratin, muscle actin, and S-100 protein. The immunohistochemical profile of epitheliosis indicates that it is primarily an epithelial proliferation with strong HMW keratin and weak S-100 protein expression but without ME cell participation. The distinct differences in HMW keratin expression of epitheliosis and intraductal carcinoma appear to reflect a consistent antigenic difference in these two biologically distinct forms of proliferation.
Assuntos
Doenças Mamárias/patologia , Neoplasias da Mama/patologia , Carcinoma in Situ/patologia , Carcinoma Intraductal não Infiltrante/patologia , Actinas/análise , Biomarcadores Tumorais , Feminino , Humanos , Hiperplasia/patologia , Técnicas Imunoenzimáticas , Queratinas/análise , Proteínas S100/análiseRESUMO
Positive staining with Hale's colloidal iron stain, or modifications thereof, is considered a diagnostic feature for chromophobe renal cell carcinoma and has been used as a discriminatory feature to differentiate it from other renal tumors. We studied colloidal iron staining in 62 cases encompassing a wide histologic spectrum of renal neoplasms (14 chromophobe renal cell carcinomas, 19 renal oncocytomas, 11 each of granular variants and conventional clear cell renal cell carcinomas, and 7 eosinophilic variants of papillary renal cell carcinoma) to investigate the specificity of the stain for chromophobe renal cell carcinoma. In cases of chromophobe renal cell carcinoma, sections from two different areas were stained to ascertain whether there was any spatial variation in staining. Influence of staining techniques on the results also was investigated by staining each case of chromophobe renal cell carcinoma using two different methods: the traditional Hale's and a modified Mowry's technique, which treats sections with 3% acetic acid before adding the colloidal iron. Our results show that positive staining with colloidal iron stain is not limited to chromophobe renal cell carcinoma, however, a diffuse and strong, reticular staining pattern was observed only in cases of chromophobe renal cell carcinoma (14 of 14). The staining patterns were less consistent in all other renal neoplasms and differed from the reaction observed in chromophobe renal cell carcinoma. Most renal oncocytomas (16 of 19) had focal and weak, fine dustlike positivity, and all clear cell carcinomas showed focal, coarse, dropletlike positive staining (22 of 22), in addition to a focal, coarse, bubbly pattern in 5 of 11 clear cell subtypes. Although all seven cases of the eosinophilic variant of papillary renal cell carcinoma showed strong, coarse, dropletlike staining, most of the positivity was coincident with the Perl's (prussian blue) reaction, indicating that the staining was due to hemosiderin, which is frequently present in this histologic subtype of renal cell carcinoma. Staining intensity did not vary considerably among different areas of chromophobe renal cell carcinoma, but the modified Mowry's method yielded brighter and sharper reticular staining, as compared with the Hale's method. Our results show that in the appropriate morphologic context diffuse and strong reticular positivity using the modified Mowry's colloidal iron stain method is highly characteristic for chromophobe renal cell carcinoma. Treatment of sections with 3% acetic acid before adding the colloidal iron gives technically superior staining results.
Assuntos
Carcinoma de Células Renais/diagnóstico , Histocitoquímica/métodos , Ferro , Neoplasias Renais/diagnóstico , Coloração e Rotulagem/métodos , Adenocarcinoma de Células Claras/diagnóstico , Adenoma Oxífilo/diagnóstico , Carcinoma Papilar/diagnóstico , Coloides , Diagnóstico Diferencial , HumanosRESUMO
Clear cell tumors of the lung (CCTL) are rare neoplasms of uncertain differentiation. A previous study of eight CCTL demonstrated a lack of epithelial features, but their exact nature remained unknown. In the current study of nine CCTL, immunohistochemistry using preliminary enzymatic digestion showed strong reactivity with the antimelanocytic markers HMB-45 (seven cases) and HMB-50 (six cases) and focal positivity for S-100 (nine cases), neuron-specific enolase (three cases), synaptophysin (one case), and Leu-7 (one case). Staining for cytokeratin, epithelial membrane antigen, chromogranin, and glial fibrillary acid protein was uniformly negative. Frozen-section immunoreactivity for vimentin and the antimelanocytic monoclonal preparation NKI/BETEB was noted in the one CCTL for which snap-frozen tissue was available. Ultrastructural examination of three glutaraldehyde-fixed CCTL showed rare neoplastic cells containing the full spectrum of melanosomes in two, one of which also contained neurosecretory-type granules. Aberrant melanosomal forms were identified in the third case. Melanosomes were not identified in the remaining five CCTL studied from formalin- or paraffin-retrieved material. The findings indicate that CCTL exhibits melanocytic differentiation. This feature may be of considerable value in distinguishing CCTL from other clear cell neoplasms.
Assuntos
Neoplasias Pulmonares/patologia , Melanócitos/patologia , Anticorpos Monoclonais/metabolismo , Antígenos de Diferenciação/metabolismo , Antígenos CD57 , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/ultraestrutura , Melanócitos/metabolismo , Melanócitos/ultraestrutura , Proteínas de Membrana/metabolismo , Microscopia Eletrônica , Fosfopiruvato Hidratase/metabolismo , Proteínas S100/metabolismo , SinaptofisinaRESUMO
Abundant granular eosinophilic cytoplasm is a common feature of renal oncocytoma, chromophobe renal cell carcinoma, eosinophilic variant of papillary renal cell carcinoma, and the granular variant of clear cell renal cell carcinoma (RCC). Each of these entities has a unique architectural pattern and a distinctive molecular or cytogenetic profile. The chief reason for their distinction from one another is the difference in their biologic behavior. Careful and thorough light microscopic examination distinguishes most cases based on individual characteristic architectural and cytomorphologic features. However, precise characterization may be difficult in some cases because of overlapping morphologic features. We evaluated the antimitochondrial antibody 113-1 in an attempt to ascertain differences in immunostaining patterns in 57 cases of granular renal tumors, including 20 renal oncocytomas, 15 chromophobe RCCs, 13 granular variants of clear cell RCC, and nine eosinophilic variants of papillary RCC. Distinctive, and nearly exclusive, staining patterns were observed among the groups, with chromophobe RCC showing peripheral accentuation of coarse cytoplasmic granules (15 of 15), renal oncocytoma with diffuse and fine granularity (20 of 20), and granular variant of clear cell RCC with irregular cytoplasmic distribution of coarse granules (11 of 13). Staining was most intense in the eosinophilic variant of papillary RCC and was generally coarsely granular and diffuse. Staining patterns also differed in clear cell areas within chromophobe RCC and the granular variant of clear cell RCC. Although clear cells in the former group showed granular staining with peripheral accentuation, most of the clear cells in the latter lacked any staining. We conclude that, in addition to distinct cytoarchitectural features, immunostaining patterns with antimitochondrial antibody 113-1 appear to be a useful discriminatory adjunct in the complex differential diagnosis of granular renal cell tumors.
Assuntos
Adenoma Oxífilo/diagnóstico , Autoanticorpos/análise , Carcinoma de Células Renais/diagnóstico , Neoplasias Renais/diagnóstico , Mitocôndrias/imunologia , Adenoma Oxífilo/patologia , Carcinoma de Células Renais/patologia , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Rim/patologia , Neoplasias Renais/patologia , Coloração e RotulagemRESUMO
Ber-EP4 is a recently characterized monoclonal antibody directed against a cell surface glycoprotein that is putatively present on human epithelial cells but lacking on the mesothelium. To investigate the diagnostic efficacy of Ber-EP4 in distinguishing adenocarcinoma from mesothelioma, we studied formalin-fixed, paraffin-embedded sections from well-documented cases of adenocarcinoma (120 cases), adenomatoid tumor (nine cases), and malignant mesothelioma (49 cases). Of the 120 adenocarcinomas, 103 (86%) showed membranous Ber-EP4 positivity, with diffuse reactivity noted in 82 cases and focal staining in 21 cases. Reactivity with Ber-EP4 was also observed in two of nine adenomatoid tumors (22%) and 10 of 49 mesotheliomas (20%). Staining in the mesotheliomas was restricted to epithelioid areas and generally focal. In one mesothelioma, however, Ber-EP4 stained the majority of neoplastic cells. In contrast to previous reports, we conclude that positivity with Ber-EP4 does not exclude the diagnosis of mesothelioma. Nonetheless, most Ber-EP4-positive mesotheliomas exhibit only focal positivity, as opposed to the extensive staining commonly observed in adenocarcinomas. Ber-EP4 has diagnostic utility in the discrimination of mesothelioma from adenocarcinoma, but it is best utilized in an antibody panel that includes other markers of carcinomatous differentiation.
Assuntos
Adenocarcinoma/diagnóstico , Anticorpos Monoclonais , Mesotelioma/diagnóstico , Adenocarcinoma/patologia , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Mesotelioma/patologiaRESUMO
In this study of 40 cases of basaloid squamous cell carcinoma, 83% arose in the pyriform sinus, base of tongue, tonsil, and larynx. The 35 men and five women ranged in age from 27 to 88 years (median 62). In patients for whom social habits were recorded, 24 of 26 patients were smokers and 22 of 25 drank ethanol. Most presented with stage III or IV disease. Twenty-seven patients had regional metastases at the time of presentation and 15 developed distant metastases. Seventeen patients died with disease (median survival 18 months). The tumors were composed of moderately pleomorphic basaloid cells forming nests, cords, and frequent cribriform patterns. Squamous dysplasia of surface mucosa, focal squamous differentiation within invasive basaloid squamous cell carcinoma, or foci of conventional squamous cell carcinoma were present, alone or in combination. All studied neoplasms were immunohistochemically positive for keratins with the 34 beta E12 antibody. Approximately 80% were immunoreactive using AE1/AE3 or CAM 5.2. Epithelial membrane antigen, carcinoembryonic antigen, and S100 protein were found in 83%, 53%, and 39%, respectively, of the cases. Diffuse, weak immunoreactivity for neuron-specific enolase was seen in 75% of tumors. Synaptophysin, chromogranin, muscle-specific actin, and glial fibrillary acidic protein were absent. Basaloid squamous cell carcinoma has been confused with adenoid cystic carcinoma and small cell undifferentiated carcinoma, but is usually distinguishable in routine hematoxylin and eosin-stained sections, or, in rare problematic cases, with the aid of immunohistochemical studies. Distinction is warranted because the biologic behavior of basaloid squamous cell carcinoma differs from that of both of these lesions.
Assuntos
Carcinoma Basoescamoso/patologia , Neoplasias de Cabeça e Pescoço/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno Carcinoembrionário/análise , Carcinoma Basoescamoso/química , Carcinoma Basoescamoso/diagnóstico , Diagnóstico Diferencial , Feminino , Neoplasias de Cabeça e Pescoço/química , Neoplasias de Cabeça e Pescoço/diagnóstico , Humanos , Imuno-Histoquímica , Queratinas/análise , Masculino , Glicoproteínas de Membrana/análise , Pessoa de Meia-Idade , Mucina-1 , Proteínas S100/análiseRESUMO
Verruciform xanthoma is a rare clinicopathologic entity of uncertain etiology that occurs primarily in the oral mucosa. Aggregates of foam cells in the submucosal stroma or papillary dermis in association with verrucous epithelial hyperplasia are the hallmark of this lesion. Extraoral (cutaneous) occurrence of verruciform xanthoma is much rarer and has been reported mostly in the genital skin. Five cases of extraoral cutaneous verruciform xanthoma (three from the scrotum, one from the penis, and one from the nose) and one histologic "simulant" (from skin of the nose) were studied. The lesions were solitary, raised, or polypoid with cup-shaped craters filled with parakeratotic cells that blended into keratinocytes of an acanthotic and papillomatous epidermis. There was a neutrophilic infiltrate of varying intensity between plump parakeratotic cells and keratinocytes, near the surface of the epidermis. Aggregates of foam cells were present in the papillary dermis, which was highly vascular. A plasma cell predominant infiltrate was seen at the base in a bandlike fashion. Despite the architectural resemblance of verruciform xanthoma to verrucous mucocutaneous lesions related to human papillomavirus infection, it was not detected by either immunohistochemistry, in situ hybridization, polymerase chain reaction, or Southern blot analysis in any case. The foam cells were weakly positive for cytokeratin and for Factor XIIIa but negative for S-100 protein. The KP1 and Mac 387 immunostain showed focal weak staining in foam cells. We postulate that a cascade of events pursue after initial keratinocytic damage attracting neutrophils, with subsequent phagocytosis of necrotic keratinocytic debris by dermal dendrocytes, eventually leading to the ultimate manifestation of the lesion as verruciform xanthoma. The etiologic agent remains elusive, but based on our findings, we conclude that verruciform xanthoma is most likely not a human papillomavirus-associated squamoproliferative lesion and that the foam cells, a histologic hallmark of the lesion, are most likely derived from dermal dendritic cells.
Assuntos
Doenças dos Genitais Masculinos/patologia , Doenças Nasais/patologia , Xantomatose/patologia , Adulto , Idoso , Biomarcadores/análise , Feminino , Doenças dos Genitais Masculinos/virologia , Humanos , Imuno-Histoquímica , Hibridização In Situ , Queratinas/análise , Ceratoacantoma/patologia , Ceratoacantoma/virologia , Masculino , Pessoa de Meia-Idade , Doenças Nasais/virologia , Papillomaviridae/isolamento & purificação , Reação em Cadeia da Polimerase , Psoríase/patologia , Psoríase/virologia , Transglutaminases/análise , Xantomatose/virologiaRESUMO
On light microscopic examination, the morphologically overlapping features of granular eosinophilic cytoplasm in renal oncocytoma and the eosinophilic variants of chromophobe renal cell carcinoma and conventional (clear cell) renal cell carcinoma may pose difficulties in diagnosis. We investigated the ultrastructure of 5 renal oncocytomas, 7 eosinophilic variants of chromophobe renal cell carcinoma, and 5 eosinophilic variants of conventional (clear cell) renal cell carcinoma. Special attention was paid to mitochondria and microvesicles and interrelations thereof. The electron microscopic features were correlated with the light microscopic findings. All of the tumors had abundant mitochondria. Although abundant microvesicles were present in all of the chromophobe renal cell carcinomas, scant numbers of microvesicles were also sometimes present in renal oncocytomas (2 of 5) and in the eosinophilic variant of conventional (clear cell) renal cell carcinoma (1 of 5). The mitochondria in all three types of renal neoplasms studied differed in morphology, being predominantly uniform and round with predominantly lamellar cristae in renal oncocytoma, variable in shape and size with predominantly tubulocystic cristae in chromophobe renal cell carcinoma, and swollen and pleomorphic with rarefied matrix and attenuated cristae in the eosinophilic variant of conventional (clear cell) renal cell carcinoma. Variable numbers of mitochondria in all of the chromophobe renal cell carcinomas had outpouchings of the outer membranes, some of which carried parts of inner membrane within them. These outpouchings closely resembled the nearby cytoplasmic microvesicles, as did the tubulocystic cristae of the mitochondria. Some microvesicles contained homogeneous, electron-dense, finely granular matrix, similar to that seen in mitochondria. In one of seven chromophobe renal cell carcinomas, microvesicles were present in rough endoplasmic reticulum, and in two others, mitochondria were present within some vesicles. These features strongly suggest a close relationship between the microvesicles and mitochondria. Based on the role of vesicle formation in normal mitochondriogenesis, and some of our observations, we propose that defective mitochondriogenesis may be the source of microvesicles in chromophobe renal cell carcinomas.
Assuntos
Adenocarcinoma de Células Claras/ultraestrutura , Adenoma Oxífilo/ultraestrutura , Carcinoma de Células Renais/ultraestrutura , Eosinófilos/patologia , Neoplasias Renais/ultraestrutura , Mitocôndrias/ultraestrutura , Vacúolos/ultraestrutura , Adenocarcinoma de Células Claras/patologia , Adenoma Oxífilo/patologia , Carcinoma de Células Renais/patologia , Núcleo Celular/ultraestrutura , Vesículas Revestidas/ultraestrutura , Citoplasma/ultraestrutura , Humanos , Neoplasias Renais/patologia , Microscopia EletrônicaRESUMO
Apocrine features occurring in sclerosing adenosis (apocrine adenosis), atypical ductal hyperplasia (ADH), and non-comedo ductal carcinoma in situ (DCIS) often add to diagnostic difficulty. We have evaluated the usefulness of DNA content determined by image analysis in apocrine metaplasia and hyperplasia, apocrine adenosis, ADH, DCIS, lobular carcinoma in situ, invasive ductal carcinoma, and infiltrating lobular carcinoma as a potential diagnostic aid in some of these problematic breast lesions with apocrine features. Infiltrating ductal carcinoma and DCIS were further subdivided into high- or low-grade category based on nuclear features. Microscopic fields containing 63 lesions were identified in slides from breast excisions. From each selected area 100 cells in corresponding fields in paired Feulgen-stained sections were digitized for computerized ploidy analysis with lymphocyte nuclei in the same slides serving as internal diploid controls. Aneuploidy was assessed using combined DNA index and modified Auer histogram criteria for DNA content abnormalities. There was strong association between the assessment of nuclear grade and ploidy (Fisher's exact test, P < .00001). All but one of the benign and low-grade malignant lesions (97%) were in the diploid range (six of seven apocrine metaplasia cases, three of three apocrine adenosis cases, 14 of 14 ADH cases, 10 of 10 low-grade DCIS cases, two of two lobular carcinoma in situ cases, and two of two infiltrating lobular carcinoma cases). In contrast, 24 of 25 (96%) of the high-grade malignant lesions were aneuploid (10 of 10 DCIS cases and 14 of 15 infiltrating ductal carcinoma cases). We conclude that DNA ploidy status does not offer additional diagnostic information to light microscopy in distinguishing among benign apocrine proliferations, ADH, and low-grade DCIS since these proliferations share a diploid range DNA content.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , DNA de Neoplasias/análise , Carcinoma in Situ/genética , Carcinoma in Situ/patologia , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Humanos , PloidiasRESUMO
The immunohistologic distribution of the basement membrane components, type IV collagen and laminin, was evaluated in 57 alcohol-fixed, paraffin-embedded tissue sections which demonstrated immunostaining patterns with antigen preservation similar to that of frozen tissue sections. Normal and hyperplastic squamous mucosa, a spectrum of intraepithelial neoplasia, and invasive squamous cell carcinomas of the upper aerodigestive tract were evaluated by this technique. Prominent and continuous basement membrane staining characterized normal and reactive hyperplastic squamous mucosa. The basement membrane varied greatly with epithelial dysplasia and was usually prominent and continuous in mild to moderate dysplasias. In severe dysplasia/carcinoma in situ, the basement membrane was often thinned and occasionally discontinuous. The distribution of basement membrane in invasive carcinomas was also varied. Basement membrane was usually present in invasive tumors with well-defined tumor host borders and cohesive patterns of stromal invasion which were interpreted as foci of histologic differentiation. In contrast, invasive carcinomas with irregular cords or single tumor cells distributed through the host stroma invariably lacked basement membrane at the tumor-stromal interface; this was interpreted as a decreased expression of histologic differentiation. We conclude that 1) severe intraepithelial neoplasia is often associated with irregularities of basement membrane and that the absence of basement membrane does not necessarily define invasive cancer; 2) immunolocalization of basement membrane in invasive carcinomas is common in areas displaying histologic differentiation; and 3) the association of basement membrane distribution and histologic pattern of tumor invasion suggests that squamous cell carcinomas are capable of undergoing focal histologic differentiation after invasion has occurred.
Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Membrana Basal/patologia , Carcinoma in Situ/patologia , Humanos , Técnicas ImunoenzimáticasRESUMO
The distinction between serous neoplasms of the peritoneum in women and conventional mesothelioma can be difficult. In order to determine any significant immunohistochemical differences, formalin-fixed, paraffin-embedded sections of 10 peritoneal serous tumors (PST), 10 ovarian serous tumors (OST), and 10 epithelial mesotheliomas were evaluated with a panel of 10 antibodies directed against carcinoembryonic antigen (CEA: polyclonal, monoclonal), high molecular weight keratin (34 beta E12), low molecular weight keratin (35 beta H11), Leu-M1, TAG-72 (monoclonal antibody B72.3), human milk fat globulin (HMFG-2), vimentin, placental alkaline phosphatase (PLAP), and S-100 protein. The antibodies CEA, Leu-M1, and B72.3 had the most discriminatory value in differentiating serous tumors from mesothelioma. Eighty-five percent of PSTs and OSTs (17 of 20) were positive with CEA, Leu-M1, and/or B72.3. None of the mesotheliomas stained for CEA or Leu-M1; three mesotheliomas had very focal positivity with B72.3 (1% or less). Vimentin, PLAP, HMGF-2, keratin, and S-100 had no significant discriminatory value. Epithelial mucin was present in 80% of serous tumors, while the mesotheliomas lacked epithelial mucin. Leu-M1, CEA, and/or B72.3 positivity in a peritoneal tumor supports a diagnosis of serous tumor. However, since some PST do not stain for any of the three antibodies and the focal nature of positive reactions in some cases may be difficult to interpret, exclusion of mesotheliomas is enhanced by the use of mucin stains.
Assuntos
Mesotelioma/patologia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fosfatase Alcalina , Anticorpos , Antígenos de Diferenciação Mielomonocítica/biossíntese , Antígenos de Neoplasias/biossíntese , Diagnóstico Diferencial , Feminino , Proteínas Ligadas por GPI , Expressão Gênica , Glicoproteínas , Humanos , Isoenzimas/biossíntese , Queratinas/biossíntese , Glicoproteínas de Membrana/biossíntese , Mesotelioma/metabolismo , Pessoa de Meia-Idade , Mucina-1 , Mucinas/biossíntese , Neoplasias Ovarianas/metabolismo , Neoplasias Peritoneais/metabolismo , Neoplasias Pleurais/metabolismo , Neoplasias Pleurais/patologia , Proteínas S100/biossíntese , Vimentina/biossínteseRESUMO
Selected papillary squamous tumors of the upper aerodigestive tract (UADT) mucosa in adult patients do not have well-defined histologic criteria and the clinical behavior is poorly understood. To better characterize this spectrum of neoplasms, UADT papillary neoplasms were evaluated by routine histology, determination of cellular DNA content using Feulgen-stained tissue sections, and the typing of human papillomavirus (HPV) by in situ hybridization. Solitary papillomas were studied in two patients; there was no recurrence in either case, both had normal DNA content, and one was typed as HPV-6 while the other was typed as HPV-11. Seven adult patients with recurrent papillomatosis and at least one biopsy with dysplasia/atypia were identified (mean age at diagnosis, 13.3 years; mean age at last contact, 42.7 years). Six of seven patients had abnormal DNA cellular content in foci of epithelial atypia. In all biopsies evaluated, the papillomas of the seven patients were consistently typed as either HPV-6 or HPV-11. Six patients with malignant papillary neoplasms also had abnormal DNA cellular content, but none revealed evidence of HPV type 6, 11, 16, or 18 by in situ hybridization of tissue sections. In many of the recurrent papillomas, the degree of epithelial atypia encountered was pronounced and was commonly misdiagnosed as carcinoma in situ or papillary carcinoma. The aneuploid DNA content of these foci of atypia reflected the abnormal cellular appearance and partially explained the overdiagnosis of malignancy. However, none of the seven patients were treated for malignant disease and none progressed to invasive carcinoma, with an average follow-up period of almost 30 years. We conclude that histologic and cytologic atypia in HPV-containing papillomatosis may be appreciable. The aneuploid DNA content may represent premalignant conditions and the patient may be at an increased risk for the subsequent development of squamous cancer. However, none of the seven patients with recurrent papillomatosis developed any evidence of malignancy. In addition, none of the patients with papillary carcinomas had previous recurrent papillomatosis.
Assuntos
Carcinoma Papilar/patologia , Neoplasias Laríngeas/patologia , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/patologia , Papiloma/patologia , Infecções Tumorais por Vírus/patologia , Adulto , Idoso , Carcinoma Papilar/microbiologia , DNA Viral/análise , Feminino , Humanos , Neoplasias Laríngeas/microbiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/microbiologia , Invasividade Neoplásica , Neoplasias Orofaríngeas/microbiologia , Neoplasias Orofaríngeas/patologia , Neoplasias Palatinas/microbiologia , Neoplasias Palatinas/patologia , Papiloma/microbiologia , Papillomaviridae/análise , Infecções Tumorais por Vírus/microbiologia , Úvula/patologiaRESUMO
Two synchronously arising primary squamous cell carcinomas (SCC) originating from separate sites in the anterior floor of mouth (FOM) and the pyriform sinus (PS) were evaluated by karyotype and fluorescence in situ hybridization (FISH) to determine whether they were of common or independent ancestry. The primary tumors were designated Henry Ford Hospital (HFH)-SCC-8a (FOM) and HFH-SCC-9a (PS), and the respective recurrent tumors after chemotherapy and radiation were designated -8b and -9b. HFH-SCC-8a and -8b were cultured and had closely related hypotetraploid karyotypes of monoclonal origin. Karyotypes could not be obtained from the second primary tumor HFH-SCC-9a or its recurrence -9b. However, we used karyotypes from HFH-SCC-8a and -8b as a guide to select FISH probes for the histological evaluation of genetic markers in tumor sections. Fluorescence in situ hybridization on metaphase chromosomes from the cell cultures was useful in modifying the tumor karyotypes. Fluorescence in situ hybridization identified a chromosome Y rearrangement that was not obvious from the HFH-SCC-8a and -8b karyotypes, and this Y rearrangement served as a unique clonal marker. Using two probes for the Y chromosome we showed that all four tumors shared the same Y rearrangement with loss of Yq (DYZ1) and retention of Ycen (DYZ3). Furthermore, FISH showed that all four tumors had the same aneuploidy patterns for chromosomes X, Y, 7, 9, 15, 16, and 17. From karyotypic and FISH analysis disomy for X and 9 centromere regions and the rearranged Y were all predicted and observed in the tumor tissue sections. Tetrasomy and trisomy for 7, 15, 16, and 17 were predicted from the karyotypes and this also was observed using FISH in all four tumors. These FISH aneuploidy patterns and the presence of a clonal Y marker in all four tumor samples indicate that the synchronous primaries and their recurrences were of monoclonal origin.
Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias de Cabeça e Pescoço/genética , Hibridização in Situ Fluorescente , Cariotipagem , Neoplasias Primárias Múltiplas/genética , Adulto , Aneuploidia , Carcinoma de Células Escamosas/patologia , Células Clonais , Rearranjo Gênico , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Neoplasias Primárias Múltiplas/patologia , Células Tumorais Cultivadas , Cromossomo YRESUMO
Mouse monoclonal antibodies (MoAbs), IKH-1 and IKH-2, were produced against cloned human melanoma cells, KHm-6, which were cultured with 12-O-tetradecanoylphorbol-13-acetate (TPA) and processed by formalin fixation and alcohol dehydration (FFAD). According to the biochemical analysis, antigenic substances which reacted with IKH-1 were 34.0-60.0 kDa glycoproteins, and those which reacted with IKH-2 were 33.5, 34.5 and 36.0 kDa glycoproteins. Immunoelectron microscopy revealed that reaction products of IKH-1 were seen in some membranous vesicles, premelanosomes and cell membrane of TPA-treated KHm-6 cells, while IKH-2 recognized only premelanosomal structures. Immunohistochemical tests revealed that IKH-1 and IKH-2 have a high sensitivity (94.0% and 85.0%, respectively) to formalin-fixed, paraffin-embedded (FFPE) tissue sections of malignant melanomas. IKH-1 had a high specificity and IKH-2 and 100% specificity to FFPE tissue sections of melanocytic lesions.
Assuntos
Anticorpos Monoclonais/análise , Biomarcadores Tumorais/análise , Melanoma/imunologia , Animais , Anticorpos Monoclonais/imunologia , Antígenos de Neoplasias/análise , Antígenos de Neoplasias/imunologia , Biomarcadores Tumorais/imunologia , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/patologia , Ensaios Clínicos como Assunto , Formaldeído , Humanos , Hibridomas/química , Hibridomas/imunologia , Hibridomas/patologia , Imuno-Histoquímica , Melanoma/química , Melanoma/patologia , Melanoma Experimental/química , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Camundongos , Microscopia Imunoeletrônica , Parafina , Acetato de Tetradecanoilforbol/farmacologia , Fixação de Tecidos/métodos , Células Tumorais Cultivadas/imunologia , Células Tumorais Cultivadas/patologia , Células Tumorais Cultivadas/ultraestruturaRESUMO
In this cost-conscious era, quality assessment activities in anatomic pathology are required not only to assure that quality practices result in satisfaction of accreditation standards but also to focus quality management to improve services in an economically competitive manner. Selected high yield monitoring activities that provide comparison to reference databases for benchmarking performance and adoption of practice variables effective in the best laboratories are recommended.