Does Immunohistochemistry Add to Morphology in Differentiating Trichoepithelioma, Desmoplastic Trichoepithelioma, Morpheaform Basal Cell Carcinoma, and Microcystic Adnexal Carcinoma?

BACKGROUND: The distinction among cutaneous basaloid neoplasms such as trichoepithelioma (TE), desmoplastic trichoepithelioma (DTE), morpheaform basal cell carcinoma (MBCC), and microcystic adnexal carcinoma (MAC) can be difficult, especially in superficial biopsies. As the treatment plan of each entity is different, accurate characterization is important for appropriate management. While TE and DTE are benign neoplasms with indolent behavior, MBCC and MAC are typically locally aggressive. The expression of several recently described immunohistochemical (IHC) markers, including p40, IMP3, and ProEx C, has not been adequately established in cutaneous neoplasms. We explored the potential utility of a broad IHC panel, including previously reported and novel markers to differentiate TE, DTE, MBCC, and MAC. DESIGN: A total of 35 archival cases [TE (n=14), DTE (n=9), MBCC (n=6), and MAC (n=6)] were stained with 9 IHC markers: p40, IMP3, ProEx C, p16, CK20, Ki-67, androgen receptor, D2-40, and beta-catenin. Tumors with >5% immunoreactivity were scored as positive. The intensity was scored on a scale from 1+ to 3+. The pattern of positivity- nuclear, cytoplasmic, membranous, or in combination; peripheral or central distribution with lesion was also recorded. RESULTS: CK20 (in contrast to prior studies) and IMP3 were negative in all cases. Likewise, with the exception of one case of TE, androgen receptor showed no immunoreactivity in all categories. No significant difference was observed in the expression of beta-catenin, p16, ProEx C, and p40 among the four groups of cutaneous neoplasms. The mean Ki-67 labeling index for MBCC (8%) was slightly higher than DTE (3%). Interestingly, the proliferation index for TE (15%) was significantly higher than that of MBCC. All six cases of MAC and 36% of TEs expressed D2-40; neither the MBCC nor DE cases showed D2-40immunoreactivity. Also, we confirmed the previously published observation of scattered CK20 positive Merkel cells in the epidermis of all cases of DTE; whereas, no Merkel cells were identified in MBCC and MAC cases. CONCLUSIONS: Except Ki-67, our IHC panel showed no significant added diagnostic utility of IHC in discriminating among TE, DTE, MBCC, and MAC. Among the four cutaneous neoplasms, DTE and MBCC show a small but discernible difference in Ki-67.

CD20, AIF-1, and TGF-beta in graft-versus-host disease: a study of mRNA expression in histologically matched skin biopsies.

Graft-versus-host disease is the leading cause of non-relapse mortality after allogeneic bone marrow transplantation. The cell-mediated immune mechanisms that underlie the pathogenesis of graft-versus-host disease remain unclear. In this study, 47 skin biopsies representing graft-versus-host disease grades 0-III, lichenoid, and sclerodermoid were included from 31 allogeneic bone marrow transplantation recipients. RNA from paraffin-embedded tissue was harvested. Transcript levels of the following markers were assessed and correlated with grade and survival: CD3, CD20, FoxP3, IL-17, gamma-interferon (IFN-gamma), transforming growth factor-beta (TGF-beta), IL-6, connective tissue growth factor (CTGF), allograft inflammatory factor-1(AIF-1), and IL-13. Levels of three markers significantly correlated with the length of survival (TGF-beta, correlation coefficient -20.8, P=0.016; AIF-1, 13.2, P=0.016; and CD20, 66, P=0.027). CD20 expression was limited to lichenoid cases. Levels of TGF-beta, AIF-1, and IFN-gamma appeared to correlate with histological progression, but did not reach statistical significance. Expression of FoxP3 correlated with worse survival, and approached statistical significance (P=0.053). Two potential mechanistic pathways were identified: the 'scleroderma' group (AIF-1 and TGF-beta) and the 'B-cell' group (CD20). Transcript levels of these markers were implicated in the progression from acute to chronic disease, and also correlated significantly with the duration of survival. Identification of these three markers may direct therapy selection with targeted agents, including the use of rituximab when B-lymphocytes are implicated.

Ovarian reserve tests and their utility in predicting response to controlled ovarian stimulation in rhesus monkeys.

Controlled ovarian stimulation (COS) is an alternative to natural breeding in nonhuman primates; however, these protocols are costly with no guarantee of success. Toward the objective of predicting COS outcome in rhesus monkeys, this study evaluated three clinically used ovarian reserve tests (ORTs): day 3 (d3) follicle-stimulating hormone (FSH) with d3 inhibin B (INHB), the clomiphene citrate challenge test (CCCT), and the exogenous FSH Ovarian Reserve Test. A COS was also performed and response was classified as either successful (COS+) or unsuccessful (COS-) and retrospectively compared with ORT predictions. FSH and INHB were assessed for best hormonal index in conjunction with the aforementioned tests. INHB was consistently more accurate than FSH in all the ORTs used. Overall, a modified version of the CCCT using INHB values yielded the best percentage of correct predictions. This is the first report of ORT evaluation in rhesus monkeys and may provide a useful diagnostic test before costly follicle stimulations, as well as predicting the onset of menopause.

Heterogeneity of breast cancer metastases: comparison of therapeutic target expression and promoter methylation between primary tumors and their multifocal metastases.

PURPOSE: A comprehensive comparison of biomarker expression between patients' primary breast carcinoma (PBC) and their metastatic breast carcinomas (MBC) has not been done. EXPERIMENTAL DESIGN: We did rapid autopsies (postmortem intervals, 1-4 hours) on 10 consenting patients who died of MBC. We constructed single-patient tissue microarrays from the patients' archived PBC and multiple different MBCs harvested at autopsy, which were immunohistochemically labeled for multiple biomarkers. Methylation of multiple gene promoters was assessed quantitatively on dissected PBC and MBC samples. RESULTS: Extensive heterogeneity was observed between PBC and their paired MBC, as well as among multiple MBC from the same patient. Estrogen and progesterone receptors tended to be uniformly down-regulated in metastases. E-cadherin was down-regulated in a subset of the MBC of one case. Variable overexpression in MBC compared with the PBC was observed for cyclooxygenase-2 (five cases), epidermal growth factor receptor (EGFR; four cases), MET (four cases), and mesothelin (four cases). No case strongly overexpressed HER-2/neu by immunohistochemistry, but eight cases showed variable protein expression ranging from negative to equivocal (2+) in different MBC. In one case, variable low-level HER-2/neu gene amplification was found. EGFR and MET overexpression were restricted to the four basal-type cancers. EGFR protein overexpression did not correlate with EGFR gene amplification. Multigene promoter hypermethylation of RASSF1a, HIN1, cyclin D2, Twist, estrogen receptor alpha, APC1, and RARbeta was overall very similar in the PBC and all MBCs in all cases. CONCLUSIONS: Therapeutic targets identified in the PBC or even some MBC may not reflect targets present in all metastatic sites.

Melanoma hyperpigmentation is strongly associated with KIT alterations.

KIT alterations have been identified in melanoma and treatment with imatinib has met with some success. However, the relationship between KIT and melanoma histology remains uncharacterized, and its role in melanoma pathogenesis unknown. We evaluated 70 melanomas from 70 patients seen at a single institution from 1997 to 2008. Cases were analyzed for KIT protein expression relative to histologic variables: subtype, sun damage, tumor infiltrating lymphocytes, melanoma in situ, vertical growth phase (VGP), location, and hyperpigmentation. Twenty-eight cases demonstrated 3+ membranous staining. Univariate analysis revealed 5 significant variables: sun damage (inverse, P = 0.015), tumor location (trunk>extremities>head and neck, P = 0.005), subtype (epithelioid>spindle, mixed>desmoplastic, P < 0.001), VGP (inverse, P = 0.024), and hyperpigmentation [22/26 (85% hyperpigmented cases) and 6/44 (14% nonhyperpigmented cases), P < 0.001]. Upon multivariate analysis, only hyperpigmentation and VGP remained statistically significant (P = 0.002, P = 0.019). Mutational analyses for KIT exons 9 and 11, and BRAF were performed on cases with 3+ labeling. Two of 27 of cases contained mutations in KIT exon 11, whereas only 1 case contained a V600E BRAF mutation, suggesting that KIT and BRAF mutations may be redundant events. Although KIT mutations were uncommon overall, pigmentation in conjunction with immunohistochemistry and nodular growth phase raised their frequency to 2 (40%) of 5 cases. We expand the context of KIT aberrations to involve areas other than acral and mucosal sites and demonstrate an inverse relationship between KIT abnormalities and sun damage. There is a strong correlation to hyperpigmentation that overrides factors including sun damage, tumor location, and histologic subtype, which may be used to identify cases with KIT aberrations.

Frequent beta-catenin nuclear labeling in sessile serrated polyps of the colorectum with neoplastic potential.

We obtained 22 sessile serrated adenomas (SSAs) and 19 hyperplastic polyps (HPs) and performed immunolabeling for cytokeratins (CKs) 7 and 20, CDX2, beta-catenin, and p53 to determine the role of these markers in aiding distinction of lesions with neoplastic potential. Patients with SSAs more frequently had a prior or coexistent tubular adenoma (P = .004) that was right-sided (P = .00001) and larger (P = .03). No difference in CK7, CK20, or p53 labeling was found after correction for colonic location. However, CDX2 labeling was significantly lower in SSAs (P = .02) and was predominantly confined to the crypt bases, whereas it was diffusely positive in HPs (P < .001). Surprisingly, aberrant nuclear labeling for beta-catenin was found in 9 (41%) of the SSAs but in none of the HPs (P < .002). We propose that beta-catenin and/or CDX2 immunolabeling may have diagnostic usefulness in the evaluation of serrated polyps. These findings also suggest that Wnt signaling has a role in SSA development.

Classification and pathology.

Soft tissue tumors are a heterogeneous group of benign and malignant processes. Some are assumed to be reactive; others are clearly neoplastic. Because of their rarity, they frequently pose diagnostic problems for surgical pathologists. Accurate diagnosis of these tumors is enhanced by knowledge of the clinical features of the given lesions and, at times, by application of immunohistochemical and molecular techniques. In this article the lesions are described essentially in accordance with the World Health Organization classification.

Microphthalmia-associated transcription factor (MiTF): Promiscuous staining patterns in fibrohistiocytic lesions is a potential pitfall.

Microphthalmia-associated transcription factor (MiTF) is used as a marker of melanocytic differentiation. However, MiTF immunoexpression has also been observed in histiocytes, macrophages, smooth muscle cells and fibroblasts, which raise the concern of fibrohistiocytic (FH) lesions being misdiagnosed as melanoma based on MiTF immunoreactivity. MiTF has been known to be positive in FH tumors, but this is the first study evaluating ninety-three fibrohistiocytic neoplasms to understand and delineate the staining pattern of MiTF in these tumors. Ninety-three cases of FH, 30 cases of melanocytic lesions, and 20 miscellaneous cases were studied. The FH cases included benign fibrous histiocytoma (BFH, n = 29), angiofibroma (AF, n = 11), fibromatosis (FM, n = 14), keloid (KE, n = 10), atypical fibroxanthoma (AFX, n = 7), dermal scar (DS, n = 9), dermatofibrosarcoma protuberans (DFSP, n = 12), and pigmented DFSP (Bednar tumor, n = 1). Benign fibrous histiocytoma were sub-categorized into dermatofibroma (n = 15) and epithelioid fibrous histiocytoma (n = 14). The melanocytic lesions included desmoplastic melanoma (DM, n = 8), melanoma in-situ (MIS, n = 5), re-excision-free of melanoma (RFM, n = 10), blue nevus (BN, n = 5), and spitz nevus (SN, n = 3). The miscellaneous category included osteosarcoma (OS, n = 3), pigmented basal cell carcinoma (PBCC, n = 5), spindle cell squamous cell carcinoma (SCA, n = 2), and giant cell tumor of tendon sheath (GCTTS, n = 10). All BFH, AF, AFX, KE, and DS cases showed a positive MiTF staining of variable extent and intensity. MiTF positivity was observed in 86% (n = 12) cases of FM and 17% (n = 2) cases of DFSP. Amongst the miscellaneous category, all cases of PBCC and GCTTS and 50% (n = 1) cases of SCA were immunoreactive for MiTF. All melanocytic lesions were positive for MiTF. None of the OS and pigmented DFSP showed positive labeling. Because of the promiscuity of MiTF labeling, awareness of its pattern in FH proliferations may avoid potential pitfalls in the diagnosis of spindle cell lesions.

The usefulness of CD71 expression by flow cytometry for differentiating indolent from aggressive CD10+ B-cell lymphomas.

We studied 34 low- and 30 high-grade CD10+ B-cell lymphomas. Forward light scatter (FSC) and CD71 fluorescence intensity (CD71i) of tumor cells were measured and normalized by corresponding values for resting T cells. Significant differences in CD71i values between low- and high-grade lymphomas were observed by the Mann-Whitney U test (P < .001) and receiver operating characteristic (ROC) curve analysis (P < .001). FSC was not significantly different between low- and high-grade lymphomas; the area under the ROC curve was less than that for CD71i. Neither FSC nor CD71i significantly differentiated follicular lymphoma (FL) grades. A comparison of all FLs (grades 1-3) and non-FL high-grade lymphomas (Burkitt lymphoma [BL] and large B-cell lymphoma [LBCL]) showed significant differences in CD71i (P < .001) and FSC (P = .021). Differences were significant in CD71i and FSC between FL and LBCL (P < .001) but not between FL and BL. CD71i is more potent than FSC for distinguishing CD10+ low- from high-grade lymphomas and FL from non-FL high-grade lymphomas. Sensitivity and specificity are limited owing to inability to identify FL3. In ROC analysis, a high value for CD71i can identify BL and LBCL with a high degree of certainty.

ProEx™ C is a useful ancillary study for grading anal intraepithelial neoplasia alone and in combination with other biomarkers.

Anal intraepithelial neoplasia (AIN) is a precursor to invasive anal squamous cell carcinoma. Histologic evaluation is hampered by intra- and interobserver variability. Various biomarkers have been investigated to improve the accuracy and reproducibility of diagnosis and grading, but interpretation can be challenging. ProEx™ C is an antibody cocktail for proteins upregulated in cervical intraepithelial neoplasia. This study investigated ProEx™ C's role alone and with p16 and Ki-67 in the diagnosis and grading of AIN. Sixty-seven anal tissue samples (22 AIN I, 25 AIN II/III, and 20 non-dysplastic) were stained for ProEx™ C, Ki-67, and p16. Staining patterns were recorded and correlated with morphologic diagnoses. Considering AIN II/III vs I, full-thickness ProEx™ C staining was more frequent in AIN II/III (p = 0.0373), and showed the highest sensitivity of the biomarkers. In combination with Ki-67, sensitivity was lower, but specificity for AIN II/III rose to 83%. For differentiating non-dysplasia from AIN I, negative ProEx™ C staining correlated with non-dysplasia (p < 0.0001) and had the highest sensitivity (90%). In combination with Ki-67, sensitivity dropped to 80%, but specificity was high (96%). ProEx™ C is useful for diagnosing and grading AIN, performing as well or better than other markers at identifying AIN II/III and non-dysplastic epithelium.

Ovarian aging and menopause: current theories, hypotheses, and research models.

Aging of the reproductive system has been studied in numerous vertebrate species. Although there are wide variations in reproductive strategies and hormone cycle components, many of the fundamental changes that occur during aging are similar. Evolutionary hypotheses attempt to explain why menopause occurs, whereas cellular hypotheses attempt to explain how it occurs. It is commonly believed that a disruption in the hypothalamic-pituitary-gonadal axis is responsible for the onset of menopause. Data exist to demonstrate that the first signs of menopause occur at the level of the brain or the ovary. Thus, finding an appropriate and representative animal model is especially important for the advancement of menopause research. In primates, there is a gradual decline in the function of the hypothalamic-pituitary-gonadal (HPG) axis ultimately resulting in irregularities in menstrual cycles and increasingly sporadic incidence of ovulation. Rodents also exhibit a progressive deterioration in HPG axis function; however, they also experience a period of constant estrus accompanied by intermittent ovulations, reduced progesterone levels, and elevated circulating estradiol levels. It is remarkable to observe that females of other classes also demonstrate deterioration in HPG axis function and ovarian failure. Comparisons of aging in various taxa provide insight into fundamental biological mechanisms of aging that could underlie reproductive decline.

Assessing the consequences of the pesticide methoxychlor: neuroendocrine and behavioral measures as indicators of biological impact of an estrogenic environmental chemical.

Japanese quail provide an advantageous avian model for assessing long-term biological consequences of endocrine disrupting chemicals (EDCs). These studies examined route of exposure and vulnerability to biological impact of EDCs over the life cycle in a precocial avian model, the Japanese quail. Embryonic exposure occurs with maternal deposition and methoxychlor (MXC) accumulated with maternal exposure. Egg injections of MXC or estradiol at selected stages of development impacted hypothalamic neuroendocrine systems in hatchlings and affected sexual maturation, with evidence for long-term effects on neurotransmitters and male behavior. Two-generation dietary studies were conducted to examine transgenerational effects of EDCs. Adult quail (P1) were exposed to dietary MXC (0, 0.5 and 5 ppm), with continued exposure in their offspring (F1), and control diet for all F2 chicks. Toxicological end points, including fertility, hatching success, and 14-day viability were unaffected. F1 and F2 male offspring from MXC-treated pairs MXC had impaired mating behavior and altered plasma hormones. These studies confirm neuroendocrine and behavioral measures as reliable indices of exposure to an estrogenic EDC. Moreover, maternal deposition remains a primary route of EDC exposure, with potential deleterious consequences for field birds, especially precocial species that appear to be particularly sensitive to embryonic EDC exposure.

Cytopathologic analysis of paraspinal masses: a study of 59 cases with clinicoradiologic correlation.

Paraspinal masses (PSM) are uncommon and present a wide spectrum of differential diagnoses on fine-needle aspiration (FNA). We analyzed 59 cases of PSM on FNA in a 15-yr period, in the context of clinicoradiologic correlation. Radiologic findings, clinical data, and tissue biopsies were reviewed. Patients were 14-83 yr of age (mean 54.7) with a M:F ratio of 1.36:1. Of the 59 cases, 39 (66%) were deemed diagnostic. Of these, 8 (21%) revealed nonneoplastic lesions and 31 (79%) yielded neoplasms: 2 (6%) benign and 29 (94%) malignant. Of the malignant cases, 22 (76%) were metastatic tumors from various sites, while 7 (24%) were cancers from local spread, which included non-Hodgkin's lymphoma (NHL, 5) and myeloma (2). Benign neoplasms were nerve sheath tumors. Metastatic tumors consisted of adenocarcinoma, 9; squamous-cell carcinoma, 3; renal-cell carcinoma, 1; and non-small-cell carcinoma/not otherwise specified (NOS), 9. Twenty-four (41%) cases received further studies: immunoperoxidase (IPOX) alone, 17 (71%); special stains for microorganisms, 2 (8%); IPOX/other special stains, 4 (17%); and flow cytometry analysis, 1 (4%). Eight (14%) cases received follow-up biopsies. Half of these biopsies added information to previously "nondiagnostic" FNAs. Of the previously "diagnostic" FNAs, tissue biopsy yielded no additional information. Cytopathologic diagnoses were consistent with the pre-FNA radiology analyses in 13 (39%) cases. In instances of radiologic and cytopathologic discrepancy (4 cases, 12%), diagnoses made by FNA reversed the initial radiologic impression of neoplasm to infection, and vice versa. PSMs are rare lesions (0.26% of total FNAs done in 15 yr at our institution). The most common lesion encountered is metastatic adenocarcinoma, followed by NHL. Ancillary studies are helpful in difficult cases. In cases of radiologic/cytopathologic discrepancy, FNA diagnoses are more accurate and decisive for patient management. The sensitivity and specificity of a PSM FNA are 88% and 75% respectively.

Endogenous versus tumor-specific host response to breast carcinoma: a study of stromal response in synchronous breast primaries and biopsy site changes.

PURPOSE: We recently described two types of stromal response in breast cancer derived from gene expression studies of tenosynovial giant cell tumors and fibromatosis. The purpose of this study is to elucidate the basis of this stromal response--whether they are elicited by individual tumors or whether they represent an endogenous host reaction produced by the patient. EXPERIMENTAL DESIGN: Stromal signatures from patients with synchronous dual primaries were analyzed by immunohistochemistry on a tissue microarray (n = 26 pairs) to evaluate the similarity of stromal responses in different tumors within the same patient. We also characterized the extent to which the stromal signatures were conserved between stromal response to injury compared to the stromal response to carcinoma using gene expression profiling and tissue microarray immunohistochemistry. RESULTS: The two stromal response signatures showed divergent associations in synchronous primaries: the DTF fibroblast response is more likely to be similar in a patient with multiple breast primaries (permutation analysis P = 0.0027), whereas CSF1 macrophage response shows no significant concordance in separate tumors within a given patient. The DTF fibroblast signature showed more concordance across normal, cancer, and biopsy site samples from within a patient, than across normal, cancer, and biopsy site samples from a random group of patients, whereas the CSF1 macrophage response did not. CONCLUSIONS: The results suggest that the DTF fibroblast response is host-specific, whereas the CSF1 response may be tumor-elicited. Our findings provide further insight into stromal response and may facilitate the development of therapeutic strategies to target particular stromal subtypes.

Significance of "signet-ring cells" seen in exfoliative and aspiration cytopathology.

"Signet ring cell" (SRC) is a phenotypic designation for a cell with a large clear cytoplasmic vacuole displacing the nucleus to the periphery. Our study focuses on the cytopathologic significance of SRCs in the context of diagnostic range, ancillary studies, and clinical prognosis. A retrospective review revealed 83 cases of SRCs diagnosed in a 16-year period (1989-2004). Clinical data and ancillary studies were reviewed. The most common specimen types consisted of abdominal and pleural SCFs (45, 54%). Of the 83 cases, 13 (16%) were benign, 65 (78%) malignant, and 5 (6%) indeterminate. Benign lesions mostly comprised of reactive mesothelial cells (9 cases, 69%). Of the malignant lesions, 47 (72%) were metastases, 14 (22%) were primary cancers and 4 (6%) were local cancer recurrences. Adenocarcinoma was the most prevalent malignant diagnosis (53, 82%). All FNAs with SRCs had a malignant diagnosis. Cytopathologic diagnoses impacted clinical prognosis and survival times. The most common site for occurrence of SRCs is abdominal fluid and their presence usually indicates malignancy (78%). Most cancers with SRCs are metastatic in origin (72%) with a significant proportion from unknown primaries (51%). Cytologic diagnoses of SRCs for cancer have 97% sensitivity and 100% specificity.

Intratumoral heterogeneity of HER-2 gene amplification and protein overexpression in breast cancer.

We report a case of a patient with invasive breast carcinoma that demonstrated HER-2 gene amplification on core biopsy, who relapsed while on adjuvant trastuzumab therapy after her mastectomy and ultimately died 15 months after diagnosis. Surprisingly, analysis of multiple metastases harvested at rapid autopsy demonstrated no evidence of HER-2 gene amplification. Retrospective examination of the carcinoma in the patient's mastectomy specimen revealed only focal HER-2 amplification within the tumor, localized to the region of the prior core biopsy site. This case highlights several important issues in HER-2 testing of breast cancer, including core biopsy-excision specimen discordance, primary-metastasis discordance, and potential selection for unamplified portions of a heterogeneously amplified tumors by trastuzumab.

Lymphoma, leukemia, and pleiocytosis in cerebrospinal fluid: is accurate cytopathologic diagnosis possible based on morphology alone?

The differentiation of benign versus malignant hematologic processes on cerebrospinal fluid (CSF) is difficult given the significant morphologic overlap and frequently scant specimen. Our study compared the diagnostic power of cytomorphologic analyses and FC analyses in the context of CSF hematologic malignancies. We identified 32 cases of CSF submitted for cytopathologic analysis with corresponding FC data, histologic, or clinical follow-up. The slides were blinded and the study participants (one hematopathologist, two cytopathologists, and one cytotechnologist) reviewed the key slides of each case without additional information. These diagnoses were compared with the original diagnoses made in the context of clinical information and ancillary studies. The spectrum of disease ranged from acute myeloid leukemia, mantle cell lymphoma, chronic lymphocytic lymphoma, Burkitt lymphoma, large cell lymphoma, T cell lymphoma, and non-Hodgkin lymphoma. Parallel diagnoses were made in 62.5% of the cases. Interestingly, the correct diagnoses were rendered in 73% of benign cases, compared with 52% of malignant cases. Of the malignant cases, there was a higher proportion of correct diagnosis based on morphology in the acute malignancies (67%) versus the chronic malignancies (47%). The sensitivity, specificity, positive predictive value, and negative predictive value were 73, 52, 60, and 66% respectively. Features most useful for diagnosis of malignancy included cellular monotony and nuclear contour irregularity. The diagnosis of malignancy based on morphology alone is difficult in CSF. Ancillary studies such as FC analyses greatly enhance the ability to accurately distinguish between benign and malignant hematologic processes.

Nasopharyngeal carcinoma: the role of the Epstein-Barr virus.

Nasopharyngeal carcinoma (NPC) arises from the epithelium of the nasopharynx and is a rare tumor in most parts of the world, including the United States. Neck swelling, nasal obstruction, and epistaxis are the most common presenting symptoms. The etiology of NPC is multifactorial and includes genetic susceptibility, exposure to carcinogens, and prior infection with the Epstein-Barr virus (EBV). We report a case of a 16-year-old African-American male who presented with hemoptysis and a 3-month history of a neck mass. Diagnostic evaluation identified a nasopharyngeal mass that upon biopsy was shown to be an undifferentiated nasopharyngeal carcinoma with immunohistochemical stains markedly positive for EBV. Recent studies have further elucidated the role of EBV in the pathogenesis of NPC and have demonstrated the utility of EBV studies in staging, prognosis, and post-therapeutic monitoring.