Maria Luisa C. Policarpio-Nicolas

Expression of alpha-methylacyl-coenzyme A racemase in nephrogenic adenoma.

Nephrogenic adenoma is a benign lesion composed of small glandular structures that develops along the urothelium with uncertain pathogenesis. Some investigators believe that nephrogenic adenoma develops by a metaplastic process in response to injury to the urothelium, while others believe that it arises from detached renal tubules. Nephrogenic adenoma may be present in the prostatic urethra and morphologically mimic prostatic adenocarcinoma. Alpha-methylacyl-coenzyme A racemase (AMACR), a recently identified prostate cancer marker, is typically negative in normal urothelium and prostatic glands, and positive in distal convoluted renal tubules in addition to prostatic adenocarcinomas. Therefore, evaluation of AMACR expression in nephrogenic adenoma will have significance in the pathologic diagnosis and in understanding pathogenesis of this lesion. We studied 38 nephrogenic adenomas by clinical, histologic, and immunohistochemical analyses for AMACR (P504S) and high molecular weight cytokeratin (34βE12). Twenty-two of 38 nephrogenic adenomas (58%) demonstrated strong cytoplasmic positivity for AMACR, ranging from patchy, focal to diffuse staining. In addition, 16 of 26 (62%) nephrogenic adenomas were negative for 34βE12. To our knowledge, this is one of the first report of a completely benign lesion, which can be found in the prostate, showing strong AMACR immunoreactivity. Our findings suggest using caution when interpreting positive AMACR immunostaining in prostatic specimens. These findings could be explained by possible renal tubular origin or renal differentiation, at least in a subset, of nephrogenic adenomas.

Tissue-preserving antibody cocktails to differentiate primary squamous cell carcinoma, adenocarcinoma, and small cell carcinoma of lung.

CONTEXT With the availability of cell type-specific therapies, differentiating primary lung squamous cell carcinomas (SCCs) and adenocarcinomas (ACAs) has become important. The limitations of small sample size and the need to conserve tissue for additional molecular studies necessitate the use of sensitive and specific marker panels on a single slide. OBJECTIVE To distinguish SCC from ACA and small cell carcinoma (SmCC) of lung using 2 novel tissue-conserving cocktails. DESIGN We compared two antibody cocktails, desmoglein 3 + cytokeratin 5/napsin A and p40/thyroid transcription factor 1 (Biocare Medical, Concord, California) in diagnosing SCC and ACA of the lung on tissue microarray, cytology, and surgical specimens. Both lung and nonlung tissue were evaluated on an 1150-core tissue microarray that contained 200 lung cancers. A microarray of 35 SmCCs and 5 small cell SCCs was also evaluated. RESULTS A cocktail of desmoglein 3 + cytokeratin 5/napsin A provided diagnostic accuracy in lung cancers with a sensitivity and specificity of 100% in SCCs and a sensitivity of 86% and a specificity of 100% in ACAs. A p40/thyroid transcription factor 1 cocktail showed p40 to have a specificity of 92% and a sensitivity of 93% in SCCs, whereas thyroid transcription factor 1 had a specificity of 100% and a sensitivity of 77% in ACAs. Cell blocks of fine-needle aspiration cytology compared with corresponding surgical (n = 20) specimens displayed similar findings. The p40 was useful in differentiating bladder from prostate carcinoma with 88% sensitivity. Isolated carcinomas from nonlung tissues were desmoglein 3 + cytokeratin 5 positive. Napsin A was positive in 22% of renal tumors as previously observed. Both cocktails were excellent in differentiating SmCCs and small cell SCCs because none of the SmCCs stained with p40. CONCLUSIONS Both antibody cocktails are excellent in differentiating primary lung ACA from SCC, as well as excluding SmCC and ACAs from all other sites on small specimens. A cocktail of desmoglein 3 + cytokeratin 5/napsin A is slightly superior compared with p40/thyroid transcription factor 1 cocktail.

Initial assessment of fine-needle aspiration specimens by telepathology: validation for use in pathology resident-faculty consultations.

Telepathology is useful when distance is an obstacle to timely diagnosis. Performance of fine-needle aspiration (FNA) at locations distant from cytopathologists can limit timely assessment of adequacy and preliminary diagnosis. We evaluated a telepathology system for consultation between residents and faculty for assessment of FNA specimen adequacy and preliminary diagnosis using 100 consecutive cases. We compared findings with the original assessment of adequacy, preliminary interpretation, and final diagnosis. Two residents initially screened 50 cases, and images were then transmitted to cytopathologists, who communicated by telephone. We found 97% diagnostic concordance and 99% accuracy. The screening time ranged from 41 seconds to 30:19 minutes (mean, 6:35 minutes). The viewing time ranged from 10 seconds to 12:50 minutes (mean, 3:52 minutes). Our telepathology system is efficient and accurate for the initial assessment and preliminary diagnosis of FNA specimens, but we recommend its use by more senior and experienced trainees.

Fine‐needle aspiration cytology of pancreatic lymphoepithelial cysts

Lymphoepithelial cysts (LECs) of the pancreas are extremely rare, benign, nonneoplastic cysts that can mimic pseudocysts or cystic neoplasms clinically and radiographically. The cytologic features of LECs have been described only in a handful of case reports and may overlap with both benign and malignant pancreatic tumors.

The use of fine needle aspiration cytology for the distinction of pancreatic mucinous neoplasia

Cytology frequently has some role in preoperatively distinguishing pancreatic mucus-producing neoplasia (intraductal papillary mucinous neoplasms [IPMNs] and mucinous cystic neoplasms [MCNs]) from other pancreatic cysts. We evaluated all cytologic specimens at our institutions from resected pancreatic cystic lesions for lesional extracellular and cellular material. Lesional extracellular material was identified in 32 of 38 of the cytologic samples from cystic pancreatic mucus-producing neoplasms (28 of 31 IPMNs and 4 of 7 MCNs). Lesional cellular material was seen in 22 of 38 cases (17 of 31 IPMNs and 5 of 7 MCNs). Lesional material was more commonly identified in higher grade and invasive lesions. Lesional extracellular material was seen in 3 of 14 samples of other pancreatic cysts, and lesional cellular material was seen in 6 of 14 cases.

Cyclin D1 and FADD as Biomarkers in Head and Neck Squamous Cell Carcinoma

Objective. Cyclin D1 and FADD (Fas-associated protein with death domain) regulate the cell cycle and apoptosis, respectively, and are located on chromosome 11q13, which is frequently amplified in head and neck squamous cell carcinoma (HNSCC). This study evaluates these proteins as predictors of clinical outcomes for HNSCC. Study Design. Historical cohort study. Setting. Academic tertiary care center. Subjects. Two hundred twenty-two patients with upper aerodigestive HNSCC. Results. Patients with tumors that were strongly positive for cyclin D1 and FADD had reduced overall (OS; P = .003 and P < .001), disease-specific (DSS; P = .039 and P < .001), and disease-free (DFS; P = .026 and P < .001) survival, respectively. Together, the 2 markers effectively stratified OS (P < .001), DSS (P < .001), and DFS (P = .002). Strong FADD staining correlated with greater alcohol consumption and varied significantly with primary tumor site: 56% of hypopharynx tumors expressed high levels of FADD but only 7% of glottis tumors. Using Cox regression analysis, FADD and N stage were significant independent predictors of DSS and DFS, whereas cyclin D1, FADD, and N stage were independently significant for OS. Conclusion. Cyclin D1 and FADD may have utility as predictors of long-term outcomes for patients with HNSCC. Further study is needed to determine if these proteins predict response to different treatment approaches or assist in selecting patients for multimodality therapy.

Cytomorphologic features of low-grade endometrial stromal sarcoma.

Endometrial stromal sarcomas are uncommon tumors of the uterus, and the cytologic features have only been reported in a number of case reports that mostly discuss the features of higher grade undifferentiated sarcomas. This article discusses the cytologic features of a large series of low-grade endometrial stromal sarcomas (ESSs) sampled by a variety of methods. We reviewed our histologic files for all confirmed cases of low-grade ESS, and followed this by a computerized search for any corresponding cytologic specimens. We identified 12 Papanicolaou tests and 9 nongynecologic specimens. Most cases showed moderate to marked cellularity with a combination of single cells and stromal fragments. Blood vessels, interspersed between the clusters of stromal cells, were seen in 15 cases; 4 of these had supporting hyaline matrix. The cells were predominantly spindle shaped with scant to moderate cytoplasm, round to ovoid nuclei, and fine chromatin. Mitotic figures and nucleoli were rare. Most cases had a clean background.

Phosphaturic mesenchymal tumor diagnosed by fine-needle aspiration and core biopsy: a case report and review of literature.

Oncogenic (tumor‐induced) osteomalacia is a rare paraneoplastic syndrome of phosphate wasting that is frequently associated with phosphaturic mesenchymal tumor (PMT). As the cytologic features of this tumor apparently have not been reported, we describe the fine‐needle aspiration (FNA) findings for PMT that arose from the gluteal soft tissue in a patient with hypophosphatemia and multiple fractures secondary to osteomalacia. Smears from the computerized tomography (CT)‐guided FNA showed groups of spindle cells having elongated nuclei, fine to moderately coarsely granular chromatin, inconspicuous nucleoli, and delicate cytoplasm. Marked nuclear atypia, mitotic figures, and necrosis were absent. The differential diagnosis included a variety of benign and malignant spindle cell neoplasms such as monophasic synovial sarcoma, leiomyoma, peripheral nerve sheath tumor, fibrosarcoma, and, less likely, metastatic melanoma and sarcomatoid carcinoma. The bland‐appearing cytologic features of a spindle cell tumor in a patient with osteomalacia should suggest the diagnosis of PMT. Diagn. Cytopathol. 2008;36:115–119.

Yolk Sac tumor with a prominent polyvesicular vitelline pattern: A report of three cases

We report 3 cases of the rare polyvesicular vitelline variant of ovarian yolk sac tumor (YST). The patients were 23, 29, and 43 years old, and all presented with large unilateral adnexal masses confined to the ovary. One tumor was predominantly cystic, and the other 2 had prominent cystic components; all 3 also had solid components. Microscopic examination of the cystic regions showed dilated cysts that largely effaced the stroma resulting in a honeycomb-like appearance. The solid foci were characterized predominantly by small tubules in a fibrous stroma; the tubules exhibited variably conspicuous cystic dilatation to merge with the microcystic appearance. The tumor cells varied from large and primitive-appearing to flattened and deceptively innocuous when lining large cysts. They were immunoreactive for &agr;-fetoprotein and glypican-3. Non–polyvesicular vitelline components of YST were present focally in 2 cases (hepatoid in one, reticular and endometrioid like in the second). Two patients are disease free after 20 and 26 years, respectively; disease-free follow-up is of short duration in the third case (2 years). The good long-term outcome in 2 cases supports prior evidence that suggests that the natural history of this form of YST may be more indolent than conventional forms of the tumor.

Cytologic findings of NUT midline carcinoma in the hilum of the lung

Nuclear protein in testis (NUT) midline carcinoma (NMC) is a clinically lethal malignancy affecting all age group often located in the midline structures such as mediastinum, larynx and nasopharynx. It is characterized by chromosomal translocation between chromosomes 15 and 19 with the formation of chimeric gene BRD‐NUT. We present the cytologic findings of NMC including the immunohistochemical stains performed. The patient is a 34‐year‐old man who presented with 1 month history of dyspnea and interscapular pain followed by nonproductive cough a week before consultation. He was initially diagnosed with pneumonia. Due to progression of symptoms, a chest CT scan was performed revealing a large hilar mass and mediastinal adenopathy. A core biopsy with touch preparations of the hilar mass was performed which revealed cohesive malignant cells with ovoid to elongated nuclei, fine to coarse chromatin pattern, irregular nuclear contour, prominent nucleoli, and scant ill‐defined cytoplasm arranged in sheets and focally pseudoglandular pattern. Although focal nuclear overlapping and crush artifact were identified, karyorrhectic debris and mitotic figures were rare. Squamous differentiation was absent. The core biopsy showed discohesive malignant cells with tumor necrosis. No nuclear molding, glandular or squamous differentiation was identified. The tumor was immunoreactive for p63 and NUT with high Ki‐67 (>80%). The tumor was negative for keratin, lymphoid, myeloid, neuroendocrine markers and S‐100. This case emphasizes that cytologic features of NMC can mimic poorly differentiated, undifferentiated and neuroendocrine carcinomas and the importance of immunohistochemical stains especially NUT monoclonal antibody in arriving at the diagnosis. Diagn. Cytopathol. 2015;43:739–742.