Resection of an Isolated Pituitary Stalk Epidermoid Cyst Through a Pretemporal Approach: Case Report and Review of the Literature.

BACKGROUND: Intracranial epidermoid cysts are congenital epidermal inclusion cysts derived from ectodermal origin with desquamated skin. The majority of these cysts occur in the cerebellopontine angle cistern. Epidermoid cyst of the pituitary stalk, however, is a rare location. To date, only 4 previous cases have been reported. CASE DESCRIPTION: A 63-year-old male presented to our clinic with migraine headaches, dizziness, increased thirst, increased urinary frequency, and impotence. Magnetic resonance imaging of the brain demonstrated a rim-enhancing cystic mass with diffusion restriction on diffusion-weighted imaging located within the pituitary stalk. The patient underwent a pretemporal approach with gross total resection of the cyst. The patient's postoperative course was uneventful with no new deficits and/or endocrinopathies. CONCLUSION: Epidermoid cyst of the pituitary stalk is an unusual and rare presentation. Four other cases treated via endoscopic approaches have been previously reported in the neurosurgical literature. To our knowledge this is the first case description of an infundibular epidermoid cyst pressing with isolated diabetes insipidus surgically treated via a transcranial pretemporal approach with gross total resection. The patient had a smooth and uneventful postoperative course with persistent diabetes insipidus.

Synchronous ipsilateral cavernous malformations of the trochlear nerve.

BACKGROUND: Cranial nerve cavernous malformations (CM) are rare benign congenital vascular anomalies, with approximately 44 preceding cases in the literature. We report the fifth case of trochlear CM, as well as the first instance of two discrete CM occurring simultaneously along the same cranial nerve. METHODS: Case report. RESULTS: A fifty-seven year-old man presented with several years of diplopia; physical examination identified a complete left trochlear nerve paralysis. MRI revealed a 1cm enhancing lesion within the left ambient cistern, and the patient underwent left pretemporal transcavernous resection. Intraoperatively, a second, discrete CM of the trochlear nerve was also discovered; wide excision of the intrinsic trochlear lesions was completed, allowing both tumors to be removed en bloc with negative margins. Pathologic analysis confirmed both to be CM of the trochlear nerve. The patient recovered with a persistent left trochlear paralysis only, and follow-up MRI was negative for residual or recurrent disease. CONCLUSION: Cranial nerve CM are rare but potentially morbid mass lesions, with the capacity to precipitate significant neuropathies. Differential diagnosis includes schwannoma and hemangioblastoma. Definitive diagnosis may not be possible preoperatively; however, resection is recommended in symptomatic patients, potentially accompanied by nerve repair.

Thyroid fine-needle aspiration cytology: performance data of neoplastic and malignant cases as identified from 1558 responses in the ASCP Non-GYN Assessment program thyroid fine-needle performance data.

BACKGROUND: Fine-needle aspiration of the thyroid is a common procedure, with an established role in reducing unnecessary thyroid surgery and identifying neoplasms and malignancies. METHODS: The study evaluated 1558 responses in the American Society for Clinical Pathology (ASCP) Non-GYN Assessment program of aspirates of thyroid neoplasms and malignancies and placed them into the following groups: group A (target or correct interpretation), group B (incorrect interpretation as a benign thyroid nodule), group C (incorrect interpretation malignant aspirate as thyroid neoplasm), and group D (malignant diagnosis with incorrect interpretation). In clinical practice, responses in groups A, C, and D would lead to surgical excision, whereas responses in group B would not. RESULTS: Of a total of 1558 responses, 78.5% of the responses were in group A, 8.5% in group B, 3.75% in group C, and 9.25% in group D. By individual diagnosis, the group rates were 86.5%, 0%, 11%, and 2.5% for anaplastic thyroid carcinoma; 83%, 5.5%, 4.25%, and 7.25% for papillary thyroid carcinoma; 79%, 7%, 6%, and 8% for medullary thyroid carcinoma; 83.5% 6.75%, 0%, and 9.75% for Hürthle cell neoplasm; and 61%, 22%, 0%, and 17% for follicular neoplasm in groups A, B, C, and D respectively. CONCLUSIONS: Fine-needle aspiration was effective in diagnosing thyroid neoplasms and malignancies and in separating thyroid nodules into surgical and nonsurgical categories. Data from a large group of cytology professionals showed good performance; however, there is room for improvement, especially in making specific diagnoses. In particular, follicular neoplasm and follicular variant of papillary thyroid carcinoma were challenging diagnoses for participants.

Expression of tissue factor in prostate cancer correlates with malignant phenotype.

Tissue factor (TF), apart from its established role in hemostasis, has been implicated in promoting angiogenesis and metastasis in a wide array of tumors including prostate cancer. Expression of TF was evaluated in freshly-resected prostate specimens obtained from patients with localized (n=9) and androgen ablated (n=6) disease using real-time reverse transcription-polymerase chain reaction and Western blot analysis. TF was detected in all specimens in both stages of the disease. We further analyzed for correlations between TF expression and those of several angiogenic growth factors and their receptors. TF RNA expression correlated significantly with expression of vascular endothelial growth factor-A in these specimens (s=0.621, P=0.013). Eighty-one prostate specimens from patients with benign prostatic hyperplasia (n=27), localized prostate cancer (ES, n=32), and advanced disease (n=22) were also evaluated using immunohistochemistry and findings were correlated with clinical parameters. TF expression was detected on epithelial cells of the malignant glands. Furthermore, its expression levels correlated significantly with Gleason score (s=0.58, P=0.0001) and with the stage of the disease (s=0.441, P=0.0001) in these specimens. These data support the role of TF in angiogenesis and disease progression.

Thrombin receptor expression is upregulated in prostate cancer.

BACKGROUND: Aberrant expression of protease-activated receptors (PARs) has been associated with increased angiogenesis, tumor growth, and metastasis of various cancers. We assessed the status of PAR1 expression in prostate cancer. METHODS: The study compared the abundance levels of PAR1 RNA and protein using real-time reverse-transcriptase polymerase chain reaction and immunoblotting in freshly resected prostate tissues from early localized-stage disease (n=9) to those from patients with advanced metastatic disease (n=7). PAR1 expression and localization was evaluated using immunohistochemical staining of prostate specimens with benign prostatic hyperplasia (n=27), early- (n=32) and advanced-stage (n=22) prostate cancer. Association analyses of PAR1 expression with expression of VEGF-family of growth factors, their receptors, and clinicopathological characteristics of the patients were also performed. RESULTS: PAR1 RNA expression in advanced-stage prostate was 2.39-fold higher (P=0.024) and its protein expression was 2.75-fold higher (P=5.89x10(-5)) when compared with early-stage prostate cancer. PAR1 expression was localized to endothelial cells in vascular network of prostate tumor areas. The expression of PAR1 correlated statistically significantly with advanced disease stage (P=0.0006) and pre-operative PSA levels (P=0.005) in these samples. CONCLUSIONS: These findings demonstrate that PAR1 expression is increased in prostate cancer. Its predominant expression in vascular network suggests that it may play a direct and crucial role in angiogenesis and could be a relevant target for therapeutic interventions to control or to prevent disease progression.

Identification of a homocysteine receptor in the peripheral endothelium and its role in proliferation.

BACKGROUND: Homocysteine, a risk factor for atherosclerosis, increases intimal hyperplasia after carotid endarterectomy with associated smooth muscle cell proliferation and modulation of cytokines. The N-methyl-D-aspartate receptor (NMDAr), a glutamate-gated ion channel receptor, is associated with homocysteine-induced cerebrovascular injury; however, the receptor has not been identified in peripheral vascular cells, nor has any interaction with homocysteine been clarified. Our objectives were first, to identify NMDAr in rat carotid artery and rat aorta endothelial cells (RAEC); and second, to determine whether homocysteine activates NMDAr in the endothelium. METHODS: NR1 and NR2A, two NMDAr subunits, were probed in rat carotid arteries by immunohistochemistry. RNA was isolated from RAECs, and expression of all NMDAr subunits (NR1, 2A, 2B, 2C, and 2D) were examined by RT-PCR and sequencing. For receptor protein expression, RAEC were incubated with different homocysteine concentrations and incubation times and also were treated with 50 microM homocysteine and/or preincubated with 50 microM dizocilpine MK-801, an NMDAr inhibitor. RESULTS: Both NR1 and NR2A were expressed in rat carotid arteries. All NMDAr subunits were expressed in the RAECs, and there was 92% to 100% similarity compared with rat NMDAr from the National Center for Biotechnology Information (NCBI) GenBank. Homocysteine upregulated NR1 expression and increased cell proliferation. RAEC pretreatment with MK-801 reduced homocysteine-mediated cell proliferation. CONCLUSION: This study is the first to show that NMDAr exists in the peripheral vasculature, and that homocysteine may act via NMDAr to increase intimal hyperplasia. CLINICAL RELEVANCE: Our objectives included the identification of a homocysteine receptor in the peripheral vasculature. The possible inhibition of a homocysteine receptor to prevent intimal hyperplasia rather than treat established stenosis would make a significant clinical impact. This will open further avenues of study in determining the role of homocysteine in the pathogenesis of intimal hyperplasia.

Stage-specific characterization of the vascular endothelial growth factor axis in prostate cancer: expression of lymphangiogenic markers is associated with advanced-stage disease.

PURPOSE: The vascular endothelial growth factor (VEGF) family plays a critical role in tumor angiogenesis and lymphangiogenesis. We characterized, at the mRNA and protein levels, the expression of VEGF-A and VEGF-D and their cognate receptors, VEGFR-1, VEGFR-2, and VEGFR-3 in early- and advanced-stage prostate cancer specimens. EXPERIMENTAL DESIGN: The levels of VEGF-A and VEGF-D mRNA in early- and advanced-stage specimens were compared using an angiogenic gene array and were confirmed by quantitative real-time PCR. Receptor protein levels and activation status were determined by immunoblotting. Spatial expression of the proteins was evaluated using immunohistochemistry with fresh and archival tissues from benign prostatic hypertrophy specimens, early-stage prostate specimens, and advanced-stage metastatic specimens. Circulating plasma levels of these growth factors were measured using ELISAs. RESULTS: We observed that expression patterns of VEGF isotypes corresponded to the prostate cancer stage: high expression of angiogenic growth factor VEGF-A was observed in early-stage prostate specimens, whereas high expression of lymphangiogenic growth factor VEGF-D was associated with advanced-stage metastatic disease. All VEGF receptors were present at variable levels in all specimens, but their activation states varied in a stage-specific manner. VEGFR-1 and, to a limited extent, VEGFR-2 were activated in early-stage specimens, whereas VEGFR-2 and VEGFR-3 were activated in advanced-stage specimens. CONCLUSIONS: Our results suggest that lymphangiogenic markers, such as VEGF-D and VEGFR-2 and VEGFR-3, may be better than angiogenic markers as targets of therapeutic intervention in advanced-stage prostate disease.

Diagnostic value of GLUT-1 immunoreactivity to distinguish benign from malignant cystic squamous lesions of the head and neck in fine-needle aspiration biopsy material.

The distinction of cystic squamous-cell carcinoma (SCC) from benign cystic squamous lesions (BCSLs) of the head and neck can be problematic on fine-needle aspiration biopsy (FNAB) material, particularly when BCSLs display epithelial reactive atypia or when SCC is well differentiated. Glucose transporter 1 (GLUT-1), a facilitative cell surface glucose transport protein, is aberrantly expressed in many cancers including oral and hypopharyngeal SCC. We evaluated the expression of GLUT-1 by immunochemistry on FNAB material to determine its value in distinguishing cystic SCC from BCSL of the head and neck. A 5-yr retrospective review of all head and neck cystic squamous lesions having FNAB specimens with cell block material, radiological studies, and histological confirmation was performed at our institution. Cell block material from 24 cystic squamous lesions, including 8 (33%) BCSL (7 branchial cleft cysts and 1 thyroglossal duct cyst[TDC]) and 16 (67%) metastatic SCCs with cystic/liquefactive degeneration, was retrieved and immunostained with anti-GLUT-1. GLUT-1 expression was considered positive when at least 10% of squamous cells exhibited distinct cell membrane reactivity. Positive GLUT-1 immunostaining was detected in all 16 SCCs and in none of the 8 BCSLs. In the carcinoma cases, the majority of malignant cells exhibited GLUT-1 reactivity; only a minor population of well-differentiated SCC cells displaying keratinization and arranged as squamous pearls did not express GLUT-1. GLUT-1 expression in cell block material can help to distinguish cystic SCCs from BCSLs of the head and neck. In conjunction with clinical and radiological correlation, GLUT-1 immunoreactivity can be an important diagnostic aid when the cytological findings are ambiguous.

Diffuse giant inflammatory polyposis: a challenging clinicopathologic diagnosis.

Giant inflammatory polyposis of the colon is an uncommon manifestation of inflammatory bowel disease. We report a unique case of localized diffuse giant inflammatory polyposis in a 58-year-old white man, which was characterized by recurrence following initial surgical resection. The patient presented with symptoms of abdominal pain and passing blood per rectum. Colonoscopic examination revealed a near-obstructing, "fungating" mass in the sigmoid colon, which clinically was thought to represent colon carcinoma. Histology of several colon biopsies revealed marked acute inflammation with microabscess formation of the polyps and the adjacent mucosa. There was no evidence of dysplasia or malignancy. Because malignancy was strongly suspected and to relieve the obstructive symptoms, the patient underwent a segmental colectomy. The histologic features of the resected mass showed giant polyps with acute inflammation diagnostic of giant inflammatory polyposis. Again, there was no evidence of malignancy. Seven months later, following an uneventful initial postoperative recovery, the patient developed a recurrence of the mass with obstructive symptoms and required further surgical resection. The gross and histologic features of the lesion were similar to the previous findings. This case highlights the varied presenting symptoms and deceptive gross colonoscopic and radiologic features of localized diffuse giant inflammatory polyposis. Finally, the presence of inflammation at the resection margins appears to predict recurrence or persistence of the disease.

A morphologic and statistical comparative study of small-cell carcinoma and non-Hodgkin's lymphoma in fine-needle aspiration biopsy material from lymph nodes.

Small-cell carcinoma (SmC) and high-grade non-Hodgkin's lymphoma (NHL) are aggressive neoplasms that require prompt diagnosis and treatment. An immediate diagnosis can be obtained using fine-needle aspiration biopsy (FNAB) material from lymph nodes (LNs), which are clinically or radiologically suspicious for tumor involvement. However, in aspirates from LNs, the cytologic distinction of SmC from NHL can be challenging. The purpose of this study was to evaluate the usefulness of various cytologic features that can be used during a rapid on-site evaluation to differentiate these two entities. Twenty-seven metastatic SmC and 50 NHLs cases diagnosed by FNAB of LNs were reviewed. All NHL diagnoses (neck, 29; abdomen, 9; axilla, 6; groin, 5; and parotid, 1) were confirmed with tissue sections, flow cytometry, or immunohistochemistry. These cases were classified as follicular, 21 (42%); diffuse large B cell, 13 (26%); small lymphocytic, 7 (14%); mantle cell, 4 (8%); anaplastic large cell, 2 (4%); and 1 each (2%), Burkitt, lymphoplasmacytic, and peripheral T-cell lymphomas. Immunochemistry confirmed the cytologic diagnoses of all SmC cases (neck, 16; mediastinum, 9; abdomen, 1; and axilla, 1) with either positive chromogranin or synaptophysin. All specimens were reviewed independently by three cytopathologists who were unaware of the original diagnoses. The presence and proportion of single (noncohesive) tumor cells, lymphoglandular bodies, nuclear fragments, paranuclear blue inclusions, nuclear molding, evenly dispersed fine-granular chromatin, crush artifact, and composition of cell clusters (monomorphic vs. polymorphic) were statistically evaluated. The presence of evenly dispersed fine-granular chromatin, paranuclear blue inclusions, and nuclear fragments was each statistically significant in differentiating SmC when compared with NHL (P < 0.01). The remaining features were not significant in distinguishing SmC from NHL in LN aspirates. The identification of distinct cytologic findings such as evenly dispersed fine-granular chromatin, paranuclear blue inclusions, and nuclear fragments can be a valuable aid to accurately diagnose and differentiate metastatic SmC from NHL in FNAB preparations from LNs.

Malignant melanoma metastatic to the liver. A cytomorphologic comparative study to identify reproducible diagnostic criteria.

OBJECTIVE: To establish cytomorphologic criteria that might facilitate the identification of malignant melanoma (MM) cells with epithelioid (nevoid) morphology, in fine needle aspiration biopsy material from the liver. STUDY DESIGN: Aspirated material from 18 cases of MM with epithelioid features and 24 cases of benign liver lesions (BLL) were examined. The cases were selected based on the availability of corresponding tissue biopsies, adequate cell block material or sufficient number of direct smears to perform immunocytochemical staining. The presence or absence of 7 cytologic criteria were reviewed, and the results were evaluated by multivariate regression analysis. RESULTS: All evaluated criteria were significant for identifying MM cells and differentiating them from reactive hepatocytes (P < .001). Uniform atypia, cell dyscohesion, eccentric nuclei and irregular nuclear membranes supported MM, whereas, monolayered sheets or cordlike arrangement; coarse, granular cytoplasm; and occasional transgressing endothelium in true tissue fragments were evidence of BLL. CONCLUSION: A systematic evaluation of the cytomorphologic features described in this study, in conjunction with the clinical and radiologic findings, can be used to render an immediate, confident and accurate diagnosis of MM metastatic to the liver.

Expression of peroxisome proliferator-activated receptor gamma in salivary duct carcinoma: immunohistochemical analysis of 15 cases.

Salivary duct carcinoma is a rare but highly aggressive tumor of the salivary glands that has poor prognosis. There is no effective cure for this tumor. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear receptor family with diverse biological functions that include mediation of adipocyte differentiation, regulation of the monocyte-macrophage anti-inflammatory activity, and inhibition of tumor cell proliferation. Natural (prostaglandin J2, PG-J2) and synthetic (thiazolinediones) PPARgamma ligands with anti-proliferative agonist activity have been identified. The expression of PPARgamma has been demonstrated in human colorectal, pancreas, breast, and prostate cancers but has never been explored in salivary duct carcinoma. The aim of our study was to investigate the expression patterns of PPARgamma in salivary duct carcinoma, a finding that may provide a mechanism for treating patients with this highly aggressive tumor. Archival formalin-fixed tissues from 15 salivary duct carcinoma cases were analyzed for PPARgamma expression by an immunohistochemical staining method using a monoclonal antibody against the PPARgamma. The tissue sections were subjected to antigen retrieval by a steam heat method. All the cases of salivary duct carcinoma originated from the parotid gland. Immunohistochemistry analyses showed positive expression of PPARgamma in 12 (80%) cases, whereas 3 (20%) were negative. Of the positive cases, 9 (75%), 2 (17%) and 1 (8%) showed strong, moderate, and weak staining, respectively. All staining was cytoplasmic. Nuclear staining was not observed. We conclude that PPARgamma is frequently (80%) expressed in salivary duct carcinoma, often at high levels, and is topographically located in the cytoplasm. The high-level expression of PPARgamma may provide a potential molecular target for the treatment of salivary duct carcinoma using agonist ligands.

Concomitant loss of mitochondria and the DNA repair protein hOGG1 in clear cell carcinoma of the kidney.

The kidney is subjected to DNA oxidative damage from reactive oxygen species generated by free radicals and toxic metabolites, leading to formation of DNA base lesions. One such DNA lesion is 8-oxoguanine, which, if not sufficiently removed, is potentially mutagenic because it can cause G:C to T:A transversion in subsequent DNA replication. The human 8-oxoguanine DNA glycosylase 1 (hOGG1) gene on chromosome 3, a region (3p25-26) that shows frequent loss of heterozygosity in clear cell renal cell carcinoma (CC-RCC), encodes for a DNA repair enzyme capable of excision repair of 8-oxoguanine. Of the known isoforms of the hOGG1 enzyme (types Ia, Ib, Ic, Id, and II), only 1, Ia, is found in the nucleus, whereas the rest show a mitochondrial distribution. We investigated, by an immunohistochemical staining method, the expression of hOGG1 protein in 40 cases of CC-RCC, using archival formalin-fixed tissue. To localize the hOGG1 enzyme in normal and tumor tissue, immuno-staining against cytochrome c, a specific mitochondrial enzyme, was also performed. The results showed marked reduction in hOGG1 expression in the majority of tumors, with complete loss of staining seen in 26 (65%) and moderate and weak positive staining present in 9 (22.5%) and 5 (12.5%) of the cases, respectively. Strong hOGG1 protein expression was present in normal tubular epithelium, located in the mitochondria. The results correlated with the expression patterns of cytochrome c. The findings indicate that loss of hOGG1 expression may have a role in development or progression of CC-RCC.

The p16 (CDKN2a/INK4a) tumor-suppressor gene in head and neck squamous cell carcinoma: a promoter methylation and protein expression study in 100 cases.

The p16 (CDKN2a/INK4a) gene is an important tumor-suppressor gene, involved in the p16/cyclin-dependent kinase/retinoblastoma gene pathway of cell cycle control. The p16 protein is considered to be a negative regulator of the pathway. The gene encodes an inhibitor of cyclin-dependent kinases 4 and 6, which regulate the phosphorylation of retinoblastoma gene and the G1 to S phase transition of the cell cycle. In the present study, p16 gene promoter hypermethylation patterns and p16 protein expression were analyzed in 100 consecutive untreated cases of primary head and neck squamous cell carcinoma by methylation-specific PCR and immunohistochemical staining. The p16 promoter hypermethylation and apparent loss of p16 protein expression were detected in 27% and 74% of head and neck squamous cell carcinoma, respectively. By chi(2) test, history of alcohol or tobacco use was significantly correlated with the loss of p16 protein expression (P =.005 and.05, respectively). When patient follow-up data were correlated with various clinical and molecular parameters, tumor size and nodal and clinical stage were the strongest prognostic predictors for disease-free survival (tumor recurrence) and for cause-specific and overall survival in patients with head and neck squamous cell carcinoma. Neither p16 promoter hypermethylation nor apparent loss of p16 protein expression appears to be an independent prognostic factor, although loss of p16 protein may be used to predict overall patient survival in early-stage head and neck squamous cell carcinoma.

Induced expression of syndecan-1 in the stroma of head and neck squamous cell carcinoma.

Syndecan-1 (CD138), a cell-surface heparan sulfate proteoglycan, is involved in cell-cell, cell-matrix interaction and growth factor binding. Loss of expression of syndecan-1 in tumor cells leads to decreased intercellular cohesion, increased potential for tumor invasiveness, and metastatic spread. Furthermore, induction of syndecan-1 expression in the tumor stroma has been postulated to promote tumor angiogenesis via its binding to growth factors such as basic fibroblast growth factor. Although syndecan-1 expression within tumor cells has been investigated in head and neck squamous cell carcinoma, stromal expression has not been studied in detail. We analyzed 38 cases of head and neck squamous cell carcinoma by immunohistochemical staining for syndecan-1 expression within the stroma. The expression of syndecan-1 within tumor cells of various histologic grades of differentiation, squamous cell carcinoma in situ cells, and benign squamous epithelium was also determined. Variable levels of diminished syndecan-1 expression were noted within the dysplastic cells of 9 of 16 (60%) squamous cell carcinoma in situ lesions and in all 38 (100%) invasive squamous cell carcinoma. In general, higher levels of syndecan-1 expression were observed in the well-differentiated tumors, in contrast to significant reduction of expression seen in poorly differentiated tumors. Syndecan-1 expression was observed within the stroma (in fibroblasts) surrounding infiltrating carcinoma cells in 28 of 38 (74%) cases. The intensity of syndecan-1 staining within the stroma showed generally an inverse correlation with the degree of tumor cell differentiation. Syndecan-1 expression was not detected in the stroma beneath normal squamous epithelium or adjacent to areas of squamous cell carcinoma in situ. We conclude that induced expression of syndecan-1 in the stroma surrounding tumor cells of invasive head and neck squamous cell carcinoma is a frequent event. The increased stromal syndecan-1 expression, coupled with its loss from the surface of carcinoma cells, may contribute to tumor cell invasion and the development of metastases.

Diagnostic utility of renal cell carcinoma marker in cytopathology.

Renal cell carcinoma (RCC) not uncommonly presents with metastases and causes diagnostic difficulty to the cytopathologist who is involved in the initial diagnostic workup of tumors with an unknown primary site. RCC marker (RCC Ma) recognizes a human proximal tubule antigen and was shown to have high specificity and relatively low sensitivity in preliminary studies on routinely processed tissue sections. We investigated the diagnostic usefulness of RCC Ma immunohistochemically in fine-needle aspiration (FNA) samples. A total of 34 FNA samples obtained from the following carcinomas were used: 7 RCCs, 5 metastatic RCCs, 4 hepatocellular carcinomas, 2 non-small cell carcinomas of the lung, 3 metastatic non-small cell carcinomas of the lung, 4 invasive ductal carcinomas of the breast, 2 pancreatic ductal adenocarcinomas, 4 metastatic transitional cell carcinomas of the urinary bladder, and 3 metastatic colon carcinomas. Routinely processed cell block sections of FNA specimens were stained with RCC Ma by using routine immunohistochemistry. Presence and distribution of staining were evaluated. Two of 7 (29%) primary and 2 of 5 (40%) metastatic RCCs showed immunoreactivity in less than 50% of carcinoma cells. Staining was focal, cytoplasmic, and granular. Scattered positive cells were present in two of the four hepatocellular carcinomas. All breast, lung, pancreas, colon, and transitional cell carcinomas were negative. RCC antibody has a low sensitivity (33%), most likely because of its focal staining pattern, and a high specificity (91%) in FNA specimens. Immunoreactivity in metastatic carcinoma of an unknown primary site, especially as part of a panel of antibodies, is useful in diagnostic cytopathology. RCC antibody has not been studied in hepatocellular carcinoma, and the significance of positivity observed in some of our cases is unclear.

Fine-needle aspiration biopsy cytology of malignant neoplasms of the sinonasal tract.

BACKGROUND: Primary and metastatic malignancies that originate in the sinonasal tract are rare and histologically diverse. The role of fine-needle aspiration biopsy (FNAB) and the cytomorphologic features of these tumors have not been specifically addressed. METHODS: The authors reviewed 22 cytology cases (20 FNABs, 1 sputum sample, and 1 pleural fluid sample) from 18 patients with malignancies originating in the sinonasal tract (17 carcinomas, 3 melanomas, and 2 sarcomas) and assessed the cytomorphology, cytohistologic correlation, and ability of cytology to render a specific diagnosis. RESULTS: Primary and metastastic sites sampled by FNAB included masses in or around the nose (n = 2), orbit (2), maxillary sinus (2), frontal sinus (1), intraoral area (1), preauricular area (1), soft tissue neck masses, parotid and lymph nodes (10), and cervical spine (1). Exfoliative cytology was positive in two samples of sputum and pleural fluid, representing the initial cancer diagnosis before the sinonasal primary tumor was detected. Seventeen of 22 (77.3%) cases were classified as carcinoma not otherwise specified, carcinoma with specific differentiation, sarcoma, or melanoma. Cytology failed to correctly classify the specific subtype of three carcinomas. The cytologic features that were evaluated included cellularity, cellular arrangement, nuclear features, nuclear-to-cytoplasmic ratio, and the background appearance. CONCLUSIONS: Sinonasal tract malignancies demonstrate a wide range of cytologic findings but specific features allowing for an accurate and definitive diagnosis are often present in many tumors. Fine-needle aspiration cytology is an important diagnostic tool in the management of sinonasal malignancies and can be complemented by the use of ancillary studies for the diagnosis of poorly differentiated or nonepithelial tumors.

Extensive somatic mitochondrial mutations in primary prostate cancer using laser capture microdissection.

Prostate cancer is the second leading cause of cancer deaths among men in the United States,but the precise molecular events leading to prostate carcinogenesis are not well understood. We isolated histologically defined cell populations from prostate cancer and its preinvasive lesions using laser capture microdissection, and performed genetic analysis on the mitochondrial genome, a sensitive cytoplasmic DNA. An extremely high incidence of somatic mutation (90% of prostatectomy cancer specimens) was found in the control region (the displacement loop) of mitochondrial DNA. The massive induction of lesion-associated mutations suggests active mitochondrial mutagenesis in both prostate cancer and its preinvasive lesions. Inspection of these mutations provides new insights into prostate cancer genetics and reveals unique patterns of somatic mutations in prostatic neoplastic lesions.

Promoter hypermethylation: an important epigenetic mechanism for hMLH1 gene inactivation in head and neck squamous cell carcinoma.

OBJECTIVE: The hMLH1 gene is one of the mismatch DNA repair genes. Inactivation of the hMLH1 gene has been implicated in the tumorigenesis of many types of human cancers. In most sporadic forms of human cancers, promoter hypermethylation is responsible for hMLH1 gene inactivation. Lack of hMLH1 protein expression has been found in a subset of head and neck squamous cell carcinomas (HNSCCs). The purpose of this study was to investigate whether promoter hypermethylation causes hMLH1 gene inactivation in HNSCCs. STUDY DESIGN: hMLH1 protein expression was determined by immunohistochemical staining in 62 cases, whereas hMLH1 gene promoter methylation was analyzed by methylation-sensitive restriction enzyme digestion, followed by polymerase chain reaction, in 35 cases of HNSCCs. RESULTS: Sixteen (26%) of 62 cases of HNSCCs showed near-complete loss of hMLH1 protein expression on immunohistochemical staining. Twelve (92%) of 13 cases that were negative for the hMLH1 protein displayed promoter hypermethylation, whereas 17 (77%) of 22 cases positive for the protein were free of promoter methylation. CONCLUSIONS: Promoter hypermethylation may be an important mechanism for hMLH1 gene inactivation in a subset of HNSCCs.

Diagnosis of histoplasmosis in urine cytology: reactive urothelial changes, a diagnostic pitfall. Case report and literature review of urinary tract infections.

Histoplasmosis not uncommonly causes systemic infection, particularly in immunocompromised patients. In systemic infection, the urinary tract is often involved, although the diagnosis of histoplasmosis in urine cytologic specimens has never been reported. Urinary tract histoplasmosis may present with gross hematuria, raising clinical suspicion for malignancy. The index case presented with intermittent gross hematuria, suprapubic pain, significant weight loss, hoarse voice, and a painful tongue ulcer. Examination of the patient revealed an ulcerated tongue lesion, an anal ulcer, a polypoid lesion on the vocal cord, and cystoscopic examination of the urinary bladder revealed erythematous patchy areas. Surgical biopsy sections from the vocal cord and tongue lesion were diagnostic of histoplasma infection. Urine cytologic examination showed atypical urothelial cells suspicious for malignancy. However, fungal stains performed on the urine specimen showed histoplasma organisms. We conclude that with a high index of suspicion, and the use of special stains, histoplasma organisms can be identified in urine.