Poorly differentiated squamous cell carcinoma of the cervix with sarcomatoid differentiation: Report of a case with cytohistological correlation.

Sarcomatoid squamous cell carcinoma (SSCC) of the uterine cervix is a rare malignancy with uncertain pathogenesis and aggressive clinical behavior. The diagnosis of this tumor poses a challenge to the cytopathologist since accurate diagnosis is based on identification of two malignant components, that is, epithelial and sarcomatoid. Most cases usually lack the sarcomatoid component on Papanicolaou test (Pap test). Therefore, a poorly differentiated carcinoma or malignant neoplasm is the most often rendered diagnosis. To date, less than 20 cases have been reported. Most of these cases were diagnosed by histopathologic findings. To our knowledge, cytomorphologic findings of SSCC on a liquid-based Pap test, with utility of cell block sections, in recognition of the two components of tumor, with follow-up histopathologic correlation have not been described. A case of SSCC occurring in a 57-year-old postmenopausal woman, describing the cytologic features on a liquid-based Pap-test, histopathologic findings of subsequent cervical biopsy, differential diagnosis, and role of ancillary studies are illustrated and discussed. Diagn. Cytopathol. 2017;45:137-142. © 2016 Wiley Periodicals, Inc.

Fibrolamellar hepatocellular carcinoma in ascitic fluid: A case report with cytohistological correlation.

The fibrolamellar variant of hepatocellular carcinoma (FL-HCC) is distinguished from other hepatocellular carcinoma's (HCC) by its unique clinical and pathological features. Cytological features of this tumor on fine needle aspiration have been described earlier. We report a rare case of a 17-year-old African American male with metastatic FL-HCC, diagnosed by body fluid cytology. The patient presented with ascites and computed tomography (CT) scan revealed multiple omental masses and liver lesions. The fluid sample was obtained along with the omental biopsy and was found positive for metastatic fibrolamellar hepatocellular carcinoma. The fluid cytology showed atypical polygonal cells with enlarged nuclei, prominent nucleoli, and abundant granular cytoplasm. Cytomorphologic features of FL-HCC presenting in body fluids have been rarely described before. This case enriches the cytopathology literature by providing awareness of this tumor presenting as metastasis in body fluids, especially in young individuals with liver lesions. Presence of a concurrent biopsy specimen provided cytohistological correlation, as it remains the gold standard for the accuracy and reliability of cytological diagnoses. Diagn. Cytopathol. 2016;44:757-760. © 2016 Wiley Periodicals, Inc.

Urinary Bladder Adenocarcinoma Metastatic to the Abdominal Wall: Report of a Case with Cytohistologic Correlation.

We report a case of adenocarcinoma metastatic to the abdominal wall in a 71-year-old man with a history of primary bladder adenocarcinoma. CT-guided core biopsy was performed; imprints and histologic sections showed malignant glands lined by tumor cells with hyperchromatic nuclei and prominent nucleoli, infiltrating through skeletal muscle. Immunohistochemistry revealed positivity for CK7, membranous/cytoplasmic ß-catenin, caudal-type homeobox transcription factor 2 (CDX2), and α-methylacyl coenzyme A racemase and negativity for CK20, p63, prostate-specific antigen (PSA), and prostate-specific acid phosphatase (PSAP). These findings were interpreted as metastatic adenocarcinoma, consistent with bladder primary. Primary bladder adenocarcinoma is a rare malignancy arising within glandular metaplasia and is associated with cystitis cystica and cystitis glandularis. Predisposing factors include bladder exstrophy, schistosomiasis, and other causes of chronic bladder irritation. This tumor is divided into intestinal, clear cell, and signet ring cell subtypes. Treatment involves radical cystectomy with pelvic lymph node dissection, and prognosis is unfavorable. Primary bladder adenocarcinoma should be differentiated from urachal adenocarcinoma, which arises from urachal remnants near the bladder dome, and secondary adenocarcinoma, or vesical involvement by adenocarcinoma from a different primary. CK7, CK20, CDX2, thrombomodulin, and ß-catenin can help distinguish primary bladder adenocarcinoma from colonic adenocarcinoma; PSA and PSAP can help distinguish primary bladder adenocarcinoma from prostate adenocarcinoma.

Follicular Thyroid Carcinoma Metastatic to the Kidney: Report of a Case with Cytohistologic Correlation.

Here we report a case of a 45-year-old female who underwent thyroidectomy for thyroid cancer and presented 20 years later with a left renal mass. CT-guided core biopsy was performed, and imprints and histologic sections of the biopsy showed cells resembling thyroid follicular cells with a background containing colloid. Immunohistochemistry revealed positivity for thyroglobulin and thyroid transcription factor 1, consistent with metastatic follicular thyroid carcinoma (FTC). The patient later underwent radical nephrectomy; histologic sections of the resected tumor revealed an encapsulated lesion morphologically similar to the biopsy specimen. Thyroid metastases to the kidney are extremely rare and are often detected during postthyroidectomy surveillance by elevation in thyroid hormone levels, (131)I scintigraphy, or (18)F-fluorodeoxyglucose uptake in positron emission tomography studies. Treatment involves total thyroidectomy, resection of the metastatic foci, and (131)I therapy. The differential diagnoses of renal metastasis of FTC include the encapsulated follicular variant of papillary thyroid carcinoma (PTC), which possesses some of the nuclear features seen in conventional PTC but may occasionally be indistinguishable from FTC in cytologic preparations, and renal lesions such as benign thyroidization of the kidney and thyroid-like follicular carcinoma of the kidney, which mimic FTC in histologic appearance but do not stain with thyroid markers.

Pleural-based neuroblastoma-like schwannoma: a case report with cytologic findings and review of literature.

We report a rare case of a 45-year-old African American woman with Neuroblastoma-like Schwannoma (Neurilemmoma) occurring in the posterior mediastinum as a pleural-based mass noted on computed tomography (CT) scan. A CT-guided core biopsy of the mass was performed and core biopsy imprints were prepared during the procedure. A Diff-Quik stain was performed for on-site evaluation of specimen adequacy. The hematoxylin and eosin (H&E) staining was evaluated subsequently. Immunohistochemistry panels were applied to the same specimen. The cytologic findings of the core biopsy imprints showed hypercellular smears with a predominance of small cells with atypical features including hyperchromatic, round nuclei and occasional nucleoli. Neurocytic rosettes were particularly appreciated on H&E stain. The immunohistochemical results exhibited strong and diffuse immunoreactivity for S-100 and vimentin. This case enriches the cytopathology literature by providing awareness of this tumor presenting as a posterior mediastinal mass.

Mucoepidermoid carcinoma of the thyroid with concomitant papillary carcinoma: comparison of findings on fine-needle aspiration biopsy and histology.

We report two cases of mucoepidermoid carcinoma (MEC) of the thyroid gland coexisting with, and possibly arising in, papillary thyroid carcinoma (PTC). In the first case, CT-guided fine-needle aspiration (FNA) was performed on a paratracheal mass representing extrathyroidal invasion of a right thyroid lobe tumor. The aspirate showed papillary fronds and cells in honeycombed arrangements with fine chromatin, enlarged nuclei, nuclear grooves, and intranuclear inclusions in a background of mucus and blood; a diagnosis of PTC was rendered initially. However, examination of histologic sections of the mass showed nests of malignant squamous cells with interspersed mucous cells and extracellular mucin, concordant with MEC, as well as PTC. A retrospective review of the FNA specimen identified MEC. In the second case, ultrasound-guided FNA was performed on a right thyroid lobe nodule. The aspirate contained two populations of epithelial cells: larger cells showing foci of both squamous and glandular differentiation that were interpreted as MEC and smaller follicular cells with nuclear changes characteristic of PTC; both were addressed in the diagnostic report. Primary MEC of the thyroid is a rare neoplasm typically exhibiting indolent clinical behavior, although our first case demonstrated extensive local invasion. It is thought to arise from squamous metaplasia associated with PTC, Hashimoto thyroiditis, or other inflammatory or neoplastic processes. In thyroid FNAs, the presence of neoplastic mucous cells and extracellular mucin plus malignant squamous cells is diagnostic of MEC. As MEC is thought to arise in PTC, the finding of the latter in these aspiration specimens is not unexpected.

Schwannoma of the oral tongue.

OBJECTIVE: To present a rare, benign lesion of the oral tongue and its treatment. STUDY DESIGN: Case presentation and literature review. METHODS: Case report. RESULTS: A 68 year old male presented with an asymptomatic lateral oral tongue lesion which had been present for several years. Fine needle aspiration was consistent with pleomorphic adenoma versus myoepithelioma. Pathology following complete surgical excision revealed schwannoma. He remains without recurrence following excision. CONCLUSIONS: Oral tongue schwannoma is a rare lesion which is treated with complete surgical excision.

Hybrid capture 2 human papillomavirus DNA testing for women with atypical squamous cells of undetermined significance Papanicolaou results in SurePath and ThinPrep specimens.

BACKGROUND: Human papillomavirus (HPV) DNA testing using Hybrid Capture 2 assay with ThinPrep Papanicolaou (Pap) collection is the only US Food and Drug Administration-approved method for the triage of women with atypical squamous cells of undetermined significance (ASCUS). Although SurePath Pap collection has been used for Hybrid Capture 2 HPV DNA testing, clinical validation of this method has been scarce. METHODS: From a cervical cancer-screening program in Mississippi, we analyzed data from screenings of 8380 women with ASCUS Pap results who underwent reflex Hybrid Capture 2 HPV DNA tests during a course of 4 years. Of these, 4145 were screened with the ThinPrep collection system, and 4235 were screened with SurePath. Results of follow-up biopsies within 3 months of Pap tests were available for the ThinPrep group (229 cases) and the SurePath group (455 cases). Hybrid Capture 2 positive rates and the follow-up biopsy results from both groups were compared. RESULTS: Hybrid Capture 2 detected high-risk HPV DNA in 68.8% of ThinPrep and 66.7% of SurePath-collected specimens (P = .37). Detection rates for CIN2+ and CIN3+ were also comparable between ThinPrep (21.4%, 3.1%) and SurePath (15.4%, 4.2%) using Hybrid Capture 2 (P = .06, P = .45). In ThinPrep-collected specimens, 4.4% were quantitatively insufficient for Hybrid Capture 2 testing. Significantly more equivocal Hybrid Capture 2 results were observed in SurePath (11.4%) than in ThinPrep specimens (3.2%). However, 67.4% of women with equivocal Hybrid Capture 2 results had negative 1-year Pap cytology follow-up in the SurePath group. CONCLUSIONS: Hybrid Capture 2 positive rates and CIN2-3 detection rates were comparable for the SurePath and ThinPrep Pap collection systems, thus supporting the use of SurePath for Hybrid Capture 2 testing.

Unusual presentation of chronic myelogenous leukemia as multiple skin chloromas: report of a case with clinical and cytologic correlation.

BACKGROUND: Chronic myelogenous leukemia (CML) presenting as multiple skin chloromas is an extremely rare manifestation. Though often seen in acute myelogenous leukemia, to date there have been no reported cases of CML presenting as multiple skin chloromas in the chronic phase. Chloromas in blastic phase of CML at different body sites have been reported previously. CASE: A 53-year-old African American male presented to his primary care provider with multiple skin nodules. A complete blood cound showed a high white cell count, for which he was transferred to a university tertiary care center. Fine needle aspiration (FNA) of the skin lesion revealed cellular smears consisting of immature myeloid cells of CML. Based on these findings, and with clinical correlation, a preliminary diagnosis of chloroma was made and confirmed by ancillary studies. CONCLUSION: This rare manifestation should alert a clinician to include CML in chronic phase in the differential diagnosis of patients presenting with multiple nonpigmented, nonpruritic skin nodules. FNA with ancillary studies can provide a rapid diagnosis.

Ductopapillary apocrine carcinoma of the eyelid metastatic to the parotid gland: report of a case diagnosed by fine-needle aspiration biopsy.

Ductopapillary apocrine carcinoma (DPAC) of the eyelid is a rare malignant neoplasm in the periocular region. The relative rarity of this tumor is a diagnostic challenge to the cytopathologist, especially when present as a metastatic lesion to an intraparotid lymph node, where the differential diagnosis includes primary parotid neoplasms, as well as various other metastatic malignancies. There are only a few reported cases of recurrent and metastatic DPAC of the eyelid, and to our knowledge, metastatic DPAC diagnosed by fine-needle aspiration biopsy (FNAB) has not been described. We report a case of a 65-year-old African-American male with a history of ductopapillary apocrine adenocarcinoma of the eyelid, diagnosed 6 weeks ago now presenting with a recurrence in the same area. Magnetic resonance imaging of the head and neck revealed an intraparotid mass also. FNAB of the parotid mass showed a well-differentiated papillary adenocarcinoma with a cystic component, similar to a previously excised ductopapillary apocrine adenocarcinoma of the eyelid.

Solitary fibrous tumor of the lung: a case report with a study of the aspiration biopsy, histopathology, immunohistochemistry, and autopsy findings.

Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm of ubiquitous location. In addition to its classic presentation as a pleural-based mass, it can be encountered in a variety of other sites. A pleural-based lung lesion can be easily accessed by radiologic guidance for cytologic study. Several reports have described the cytologic findings of SFT at various locations, including the lung. However, diagnostic difficulties can occur due to unusual clinical, radiologic, atypical cytomorphologic, and histologic features. We describe a case of intrapulmonary SFT in which a false-positive malignant diagnosis was rendered on fine-needle aspiration biopsy and concurrent surgical core biopsy prior to radiofrequency ablation. The patient died of procedural complications, and an autopsy was performed. Retrospective study of the case, especially correlation of cytologic, histologic, autopsy findings, and immunohistochemistry results were helpful in correctly diagnosing the case as SFT. We are reporting this case with emphasis on avoiding diagnostic pitfalls by being familiar with the accepted cytohistologic features and appropriate immunohistochemical results.

Tibial adamantinoma with local recurrence and pulmonary metastasis: report of a case with histocytologic findings.

BACKGROUND: Adamantinoma is a rare primary bone neoplasm of low malignant potential that may recur or metastasize in a mall percentage of patients. The myriad histologic patterns may cause difficulty in distinguishing this tumor from other primary or metastatic neoplasms. The cytomorphologic findings of fine needle aspiration biopsy were reported previously in only a small number of cases. CASE: A 32-year-old man presented with a mass in the distal side of the left leg that was diagnosed as classic adamantinoma by open biopsy. Local recurrence and pulmonary metastases were confirmed by fine needle aspiration biopsy, which showed low grade, uniform cells with nuclear membrane grooves. The patient underwent a below-the-knee amputation and is receiving palliative treatment for progressive pulmonary spread. CONCLUSION: The diagnosis of adamantinoma requires knowledge of compatible clinical and radiologic studies as well as understanding of the variable histologic patterns that one may encounter. Fine needle aspiration biopsy is particularly useful in the diagnosis of recurrent and metastatic adamantinoma. This case report describes a distinctive cytomorphologic feature of nuclear grooves that may be a useful aid in distinguishing the tumor cells of adamantinoma from other cell types.

Fine needle aspiration biopsy of vertebral and paravertebral lesions: retrospective study of 124 cases.

OBJECTIVE: To evaluate the diagnostic value of image-guided fine needle aspiration biopsy (FNAB) in the diagnosis and management of vertebral and paravertebral lesions and to review similar studies in the literature. STUDY DESIGN: One hundred twenty-four FNAB cases (113 [corrected] patients) of vertebral and paravertebral lesions occurring over a 10-year period were retrieved from the archives of the University of Mississippi Medical Center for review and clinico-radiologic correlation. Thirty-four of the cases included a concurrent core needle biopsy sample, 15 cases had subsequent surgical specimens, while 32 cases had previously established malignancy. The age range was 11 days to 91 years (mean, 46 years), with 57 male patients and 56 female. RESULTS: One hundred five cases were vertebral lesions, and 19 cases were paravertebral lesions. FNAB diagnosis were malignant in 33.87% of cases, benign in 5.64%, suspicious in 4.03%, infectious/inflammatory and degenerative in 12.91%, unsatisfactory in 16.13% and negative in 27.42%. The overall sensitivity of the procedure was 89.3% and the specificity, 93.8%. The positive predictive value was 95.7% and negative predictive value, 85.2%. CONCLUSION: FNAB is an effective means of establishing a definitive diagnosis of vertebral and paravertebral lesions, allowing appropriate patient management. Cell blocks, core biopsies and ancillary studies are useful adjuncts in rendering the diagnosis.

Accuracy of liquid-based Pap tests: comparison of concurrent liquid-based tests and cervical biopsies on 782 women with previously abnormal Pap smears.

OBJECTIVE: To evaluate the diagnostic performance of a liquid-based Pap test, the ThinPrep Pap test (TP) (Cytyc Corp., Boxborough, Massachusetts, U.S.A.), by comparing concurrent TP and cervical biopsy results on 782 patients who were referred for colposcopy because of previously abnormal conventional Pap smears (CPs). STUDY DESIGN: The ability of TP diagnoses of atypical cells of undetermined significance (ASC-US) and squamous intraepithelial lesions (SILs) to predict biopsy diagnoses of cervical intraepithelial neoplasia (CIN) was analyzed using chi2 and McNemar tests. RESULTS: The rate of agreement between diagnoses of SIL by TP and CIN by biopsy was 74.7%. ASC-US accounted for 16.0% of TP diagnoses. ASC-US had biopsy diagnoses of CIN 1 in 60% and CIN 2/3 in 12.8% of cases. For TP diagnosis of low grade SIL, biopsy diagnoses of CIN 2/3 were found in 13.5% of cases. For TP diagnoses of ASC-US and higher, the proportions of TP and cervical biopsies in comparable diagnostic categories were statistically significant (p < 0.001), with TP having sensitivity of 89.4% and positive predictive value of 89.7% for the detection of CIN. The false positive rate for TP was 8.1%, but rescreening confirmed the presence of abnormal cells in 51 of 63 (81.0%) cases of ASC-US or higher having negative biopsies. TP had a false negative rate of 8.3% and negative predictive value of 61.3%. Rescreening showed that most (77.6%) of the false negative TP specimens failed to have abnormal cells on the slides. CONCLUSION: For patients having previously detected cervical abnormalities by CP, concurrent TP demonstrated the following: (1) that it has high diagnostic accuracy for SIL, (2) that ASC-US was diagnostically equivalent to LSIL, and (3) that false negative TP for SIL can be attributed primarily to sampling rather than cytotechnologists' screening errors.

The predictive value of p16(INK4a) and hybrid capture 2 human papillomavirus testing for high-grade cervical intraepithelial neoplasia.

We performed p16(INK4a) immunocytochemical analysis and Hybrid Capture 2 (HC2; Digene, Gaithersburg, MD) high-risk HPV testing on 210 abnormal SurePath (TriPath Imaging, Burlington, NC) Papanicolaou specimens diagnosed as low-grade squamous intraepithelial lesion (LSIL) or high grade squamous intraepithelial lesion (HSIL). The results were compared with 121 follow-up biopsy specimens. p16(INK4a) was positive in 57.9% of women with LSIL compared with 97.1% of women with HSIL. In contrast, HC2 testing was positive in 85.0% of women with LSIL and 86.4% of women with HSIL. The differences in the positive rates for16(INK4a) between LSIL and HSIL was significant (P < .001), whereas, for HC2, it was not (P = .264). In patients who had cervical biopsies following a cytologic diagnosis of LSIL, the positive predictive value (PPV) of p16(INK4a) for a biopsy of cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3; 33.3%) was significantly higher than the PPV of HC2 results (21.2%) (P < .001). Using liquid-based cytology specimens, p16(INK4a) immunocytochemical analysis has a higher PPV than reflex HC2 HPV testing for identifying CIN2/3 among patients with LSIL and might be useful for selecting patients with LSIL for colposcopy.

Role of cytochrome P450 2B1 in puromycin aminonucleoside-induced cytotoxicity to glomerular epithelial cells.

Puromycin aminonucleoside (PAN)-induced glomerular injury in rats mimics minimal-change nephrotic syndrome (NS) in humans. We have demonstrated an important role of cytochrome P450 (CYP) as a significant source of catalytic iron in this model of NS. The current study was designed to identify CYP isozyme(s) present in the rat glomerular epithelial cells (GEC) and to explore the role of the specific CYP isozyme in PAN-induced cytotoxicity. CYP2B1 was identified in GEC by immunocytochemistry and Western blot. Treatment of GEC with PAN resulted in a marked generation of hydrogen peroxide (H(2)O(2)) and reduction of CYP2B1 content associated with significant increase in catalytic iron and hydroxyl radical formation. Preincubating GEC with CYP2B1 inhibitors (piperine and cimetidine) and H(2)O(2) scavenger (pyruvate) significantly reduced H(2)O(2 )generation, preserved CYP2B1 content, prevented the increase in catalytic iron and hydroxyl radical formation including PAN-induced cytotoxicity. We also observed the induction of heme oxygenase (HO-1) in PAN-treated GEC, and this up-regulation was reduced by pretreatment of the CYP inhibitors and pyruvate. Our data thus indicate an important role of CYP2B1 in PAN-induced cytotoxicity by serving as a site of reactive oxygen metabolite generation and a significant source of catalytic iron.

Pediatric medullary carcinoma of the thyroid with point mutation of RET proto-oncogene associated with multiple endocrine neoplasia and initially diagnosed by fine-needle aspiration biopsy.

A 7-year-old girl presented with a thyroid mass, elevated serum levels of calcitonin and carcinoembryonic antigen, as well as multiple mucosal nodules in the upper lip and tongue. Cytologic material obtained by fine-needle aspiration biopsy from the thyroid mass was diagnosed as medullary carcinoma and confirmed by immunohistochemical studies in the cell-block sections. Subsequent histopathologic examination showed involvement of both thyroid lobes by medullary carcinoma, and electron microscopic studies further confirmed the diagnosis. Molecular studies showed a point mutation in amino acid 918 in exon 16 of the RET proto-oncogene. Biopsies from the upper lip and tongue showed mucosal neuromas. Fine-needle aspiration biopsy is frequently used in the initial evaluation of thyroid nodules. This case illustrates the value of fine-needle aspiration biopsy as a safe and accurate diagnostic modality in the workup of pediatric thyroid nodules. Fine-needle aspiration biopsy should always be considered for the investigation of thyroid nodules in pediatric patients.

Blastomycosis: The great pretender can also be an opportunist. Initial clinical diagnosis and underlying diseases in 123 patients.

Clinically, blastomycosis can be difficult to recognize even in the endemic areas where clinicians are aware of this problem. In only 18% of 123 patients from the University of Mississippi Medical Center (Jackson, MS) blastomycosis was correctly suspected at the initial patient evaluation. Pneumonia sensu latu (40%), malignant tumors (16%), and tuberculosis (14%) were the most common misdiagnoses. The false first impression frequently resulted in unnecessary surgeries or treatment delays, with patients receiving inefficient antibiotic therapy for months. The presence of cutaneous involvement by the disease makes its' recognition easier for the clinician, raising the percentage of correct initial diagnosis to 64%. To evaluate the association with immunodepression, the presence of other diseases was also searched among the 123 patients. An immunodepressive condition preceded the fungal disease in 25% of patients. Another associated disease commonly found in blastomycotic patients was diabetes mellitus (22%). Blastomycosis is correctly suspected at the first clinical evaluation in only a small percentage of patients; pneumonia, cancer, and tuberculosis are the most common clinical considerations. Cutaneous involvement leads the clinician to the correct diagnosis in the majority of cases. One fourth of the patients with blastomycosis had underlying immunodepressive conditions, and underlying diabetes mellitus is present in 22% of patients.

Effect of cytochrome P450 2E1 inhibitors on cisplatin-induced cytotoxicity to renal proximal tubular epithelial cells.

BACKGROUND: We have demonstrated an important role of cytochrome P450 (CYP) as a significant source of catalytic iron in reactive oxygen species (ROS)-mediated cisplatin (CP)-induced renal injury. MATERIALS AND METHODS: The current study was designed to explore the role of CYP2E1 as a site for ROS generation and a source of iron in CP-induced cytotoxicity to the LLC-PK1 cells. RESULTS: CYP2E1 was identified in the LLC-PK1 cells. Exposure of LLC-PK1 cells to CP resulted in marked generation of hydrogen peroxide (H2O2), reduction of CYP2E1 content, increase in catalytic iron and hydroxyl radical formation accompanied by significant cytotoxicity. CYP2E1 inhibitors markedly reduced H2O2 generation with the preservation of CYP2E1 content, markedly decreased in iron and hydroxyl radical formation associated with significant attenuation in cytotoxicity. CONCLUSION: CYP2E1 plays an important role in CP-induced cytotoxicity by severing as a site for the generation of ROS and a significant source of catalytic iron.