Papillary adenocarcinoma of lung with psammoma bodies: report of a case derived from type II pneumocytes

A 52-year-old woman underwent thoracotomy for the removal of a mass in the middle lobe of the right lung. Light microscopy showed a tumour with the morphology of a papillary adenocarcinoma with numerous psammoma bodies. Electron microscopy revealed the tumour cells to possess the lamellated intracytoplasmic inclusions characteristic of normal and neoplastic type II pneumocytes. Psammoma bodies have not previously been reported in type II cell carcinoma of the lung. Alveolar cell carcinoma should be considered in the differential diagnosis of a papillary adenocarcinoma with psammoma bodies occurring in the lung.     

Follicular lymphoma transformed to “double‐hit” B lymphoblastic lymphoma presenting in the peritoneal fluid

Lymphomas showing both MYC/8q24 rearrangement and IGH@BCL2/t(14;18)(q32;q21), also referred to as “double‐hit” or “dual‐hit” lymphomas (DHL) are rare B‐cell malignancies with a germinal center B‐cell immunophenotype and heterogeneous cytologic and histologic features. Such lymphomas may arise de novo or through transformation of follicular lymphomas and are classified either as “B‐cell lymphoma, unclassifiable, with features intermediate between diffuse large B‐cell lymphoma (DLBCL) and Burkitt lymphoma (BL)” (most commonly), DLBCL, or, rarely, as B‐lymphoblastic lymphoma. We report a case of B‐lymphobastic lymphoma arising through transformation of follicular lymphoma diagnosed on peritoneal fluid cytology, flow cytometry, and cytogenetic studies in a 53‐year‐old man who presented with abdominal pain, shortness of breath, night sweats, extensive lymphadenopathy, pleural effusion, and ascites. Cytologic examination of the ascitic fluid showed two distinct populations of neoplastic lymphoid cells, a predominant population of larger cells with fine powdery (“blastic”) chromatin, visible to prominent nucleoli and occasional small cytoplasmic vacuoles and a less numerous population of smaller cells with centrocytic morphology. Flow cytometry also showed two distinct monotypic B‐cell populations, both expressing CD10, and TdT‐positivity was demonstrated immunohistochemically. Fluorescence in situ hybridization (FISH) demonstrated both MYC rearrangement and IGH/BCL2 gene fusion and cytogenetic analysis showed a complex karyotype including both t(14;18)(q32;q21) and t(8;22)(q24.1;q11.2). Since DHL pursue an aggressive clinical course, respond poorly to therapy, and have a poor outcome, it is important to suspect the diagnosis when encountering neoplastic lymphoid cells that are difficult to classify in effusion cytology specimens and to order the appropriate immunophenotyping and cytogenetic studies. Diagn. Cytopathol. 2013;41:986–990. © 2012 Wiley Periodicals, Inc.     

Endobronchial ultrasound‐guided transbronchial needle aspiration diagnosis of mediastinal lymph node metastasis of mucinous adenocarcinoma: Arborizing stromal meshwork fragments as a diagnostic clue

Endobronchial Ultrasound‐Guided Transbronchial Needle Aspiration (EBUS‐TBNA) is a reliable and accurate method for the diagnosis of mediastinal metastases in patients with pulmonary and extrathoracic neoplasms. We report the cytopathologic findings of a case of metastatic signet‐ring cell carcinoma with abundant extracellular mucin production in the mediastinal lymph nodes of a 41‐year‐old woman, who presented with nausea, abdominal pain, and weight loss. Imaging studies showed a renal mass, numerous lung nodules, and mediastinal and retroperitoneal lymphadenopathy. EBUS‐TBNA of level 4R and 7 lymph nodes showed abundant, thick, “clean” mucus with entrapped ciliated bronchial cells, rare histiocytes, and fragments of cartilage. No neoplastic cells could be identified in Diff‐Quik®‐stained smears during the rapid on‐site evaluation, but rare signet‐ring cells were identified in the Papanicolaou‐stained smears and cellblock sections. A distinctive feature of the aspirates was the presence of large branching (arborizing), “spidery” stromal fiber meshwork fragments. These stained metachromatically (magenta) with Romanowsky‐type stains and cyanophilic to orangeophilic with Papanicolaou stains and showed occasional attached bland spindle cells, but had no capillary lumina or CD31‐staining endothelial cells. The tumor cells were strongly and diffusely positive for CEA, CDX2, CK7, CK20, and MUC2, supporting the diagnosis of a metastatic signet‐ring cell adenocarcinoma, most likely of gastrointestinal origin. We believe that the presence of the large spidery stromal fiber fragments is a useful clue to the presence of a mucinous neoplasm in EBUS‐TBNA and allows the differentiation of the neoplastic mucus from contaminating endobronchial mucus. Diagn. Cytopathol. 2013;41:896–900. © 2012 Wiley Periodicals, Inc.     

Cytologic features of pancreatic adenocarcinoma with “vacuolated cell pattern.” report of a case diagnosed by endoscopic ultrasound‐guided fine‐needle aspiration

The “vacuolated cell pattern” has only been recently described as a distinct morphologic variant of pancreatobiliary adenocarcinoma. Herein, we report the endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) cytologic features of a case of pancreatic adenocarcinoma with “vacuolated cell pattern” occurring in a 60‐year‐old man. The aspirate smears and cell block sections from the EUS‐FNA of a 23.5 mm hypoechoic pancreatic head mass were highly cellular, showing variably‐sized crowded three‐dimensional cell clusters, flat sheets, and numerous highly atypical single cells. The background was bloody and showed necrotic debris, but no discernible mucus. The most striking feature of the aspirate was the presence of numerous very large (20–50 µm) vacuoles, occupying the entire cytoplasm, pushing the nuclei to the side and indenting them, that imparted a cribriform appearance to the sheets of neoplastic cells. The non‐vacuolated neoplastic cells were large, had abundant dense (squamoid) cytoplasm, irregularly contoured hyperchromatic nuclei, and prominent macronucleoli. Histologic evaluation of the pancreatectomy specimen showed a “vacuolated cell pattern” adenocarcinoma composed of poorly formed glands, solid sheets, and infiltrating single cells with pleomorphic nuclei and large cytoplasmic vacuoles. To our knowledge, this is the first report describing the cytologic features of this rather uncommon morphologic variant of pancreatic adenocarcinoma. Recognition of this morphologic variant of pancreatic adenocarcinoma in ESU‐FNA samples allows its differentiation from primary and metastatic signet‐ring cell carcinomas. Diagn. Cytopathol. 2014;42:302–307. © 2014 Wiley Periodicals, Inc.     

Cytomorphologic features of metastatic urothelial carcinoma in serous effusions

Metastatic urothelial carcinoma (UC) to serous effusion (SE) is extremely rare and its cytomorphological features have only been described in case reports. In this study, we searched the pathology database at University of Michigan for SEs due to metastatic UC in the last 20 years. A total of 25 cases from 20 patients with clinically and pathologically confirmed metastatic UC in SEs were retrieved. The specimens consisted of 15 pleural, 8 peritoneal, and 2 pericardial effusions. Smears were reviewed and evaluated for the following features: cellularity, single cells, cell clusters or short cords, cell wrapping, “windows” between the cells, two‐tone cytoplasm, cytoplasmic vacuoles, signet ring cells, nuclear to cytoplasmic (N/C) ratio, nuclear hyperchromasia, irregular nuclear membrane, nuclear centricity, double or multiple nuclei, nucleoli, anaplastic cells and mitosis. Our results showed that UC manifested in SEs predominantly as a single cell population with or without clusters or short cords, and frequently exhibited the “cell wrapping” of two or more cells. Individual UC cell in SEs exhibited nuclear enlargement with increased N/C ratio, irregular nuclear membranes, hyperchromatic coarse chromatin and frequently prominent nucleoli. Double or multinucleated cells, cells with vacuolated cytoplasm or signet ring appearance were also frequently present. Our results demonstrated that while certain features could suggest the diagnosis of UC, the cytomorphological features are not specific and often overlap with those of reactive mesothelium, mesothelioma, metastatic adenocarcinoma, or squamous cell carcinoma in SEs. Accurate diagnosis of UC rests on the combination of clinical history, cytomorphologic features and appropriate immunohistochemical panel. Diagn. Cytopathol. 2013. © 2012 Wiley Periodicals, Inc.     

Follicular variant of papillary carcinoma of the thyroid: Fine-needle aspirates with histologic correlation

Crile and Hazard reported in 1953 a follicular pattern of papillary thyroid carcinoma. Little has been said about this pattern in the cytologic literature. From more than 8,000 thyroid aspirates in our files, we reviewed all those diagnosed as “follicular variant of papillary carcinoma,” “suspect follicular variant of papillary carcinoma,” and “follicular neoplasm vs. follicular variant of papillary carcinoma.” Also, we reviewed all aspirates in which a diagnosis of follicular variant of papillary carcinoma had been made on surgically excised glands, regardless of the cytologic diagnosis; 63 aspirates from 45 patients were collected. All smears were air-dried and stained with Diff-Quik. Most smears were very cellular (“tumor cellularity”), and the neoplastic follicular cells formed empty follicles, rosettes, tubules, and papillary structures. Nuclei were twice the size of red blood cells, had smooth contours, were hyperchromatic, and varied in shape but not much in size. Nuclear overlapping was common. Some nuclei had one small and almost pointed end, thereby resembling arrowheads. Intranuclear inclusions, multinucleated histiocytes, and psammoma bodies were uncommon. Pink-stained colloid was frequent. Diagn. Cytopathol. 16:207–213, 1997. © 1997 Wiley-Liss, Inc.     

Cytology of metastatic cervical squamous cell carcinoma in pleural fluid: Report of a case confirmed by human papillomavirus typing

Cervical squamous cell carcinomas are rarely the cause of malignant effusions. Their identification can be relatively easy when keratinizing atypical squamous cells are present, but may be very difficult when only nonkeratinizing malignant cells are present. We present the case of a 47‐year‐old woman who presented with a large left pleural effusion after having recently completed chemoradiation therapy for stage IIB cervical squamous cell carcinoma. Cytologic examination of the fluid showed a uniform population of single atypical cells with finely vacuolated cytoplasm, ectoendoplasmic demarcation, cell‐in‐cell arrangements, and short rows of cells with intervening “windows,” all features reminiscent of mesothelial cells. No keratinization or three‐dimensional cell clusters were identified. A panel of immunohistochemical stains was performed on the cell block material, and the atypical cells were positive for cytokeratin 5/6, p63, and p16 but not for cytokeratin 7, calretinin, WT1, or Ber‐EP4 or TTF1. These findings were consistent with metastatic squamous cell carcinoma. HPV DNA determination and typing by PCR confirmed the presence of HPV16 in an aliquot of pleural fluid. This is to our knowledge the first reported case of pleural fluid involved by metastatic squamous cell carcinoma where HPV DNA testing was used to confirm the origin of the metastasis. Despite its rarity, metastatic nonkeratinizing squamous cell carcinoma should be considered when a single cell population of large atypical cells is found in effusions. Immunoperoxidase stains and HPV testing can be performed to establish the diagnosis and confirm the origin from a cervical primary. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Fine-needle aspiration cytology of metastatic ovarian carcinoma to the breast

Metastatic ovarian carcinoma to the breast is rare. It represents a diagnostic challenge to the cytologist. It usually signifies a progressive widespread metastatic ovarian tumor with a poor prognosis. This report evaluates the breast fine-needle aspiration (FNA) cytomorphologic features of six cases of metastatic ovarian carcinoma and compares them to those reported in the literature. The cytologic features included hypercellularity, abundant papillary fragments, and necrotic background. The tumor cells showed high nuclear/cytoplasmic ratio, anisonucleosis, prominent nucleoli, and psammoma bodies in cases of serous papillary carcinoma. In addition, the clear-cell carcinoma had prominent finely vacuolated and clear cytoplasm, multinucleated giant cells, and papillary fragments with hobnail nuclei. Recognition of these unusual patterns in a breast FNA cytology should raise the suspicion of a metastatic ovarian tumor. Direct comparison between the breast FNA cytology and the original primary ovarian tumor should confirm the diagnosis. The proper diagnosis of metastatic ovarian cancer to the breast will prevent unnecessary surgical treatment and ensure the appropriate therapy. Diagn Cytopathol 1996;15:1–6. © 1996 Wiley-Liss, Inc.     

“Cercariform” cells: A clue to the cytodiagnosis of transitional cell origin of metastatic neoplasms?

The “cercariform” cell is described as a distinct cytomorphologic clue that may be helpful in the diagnosis of metastatic transitional cell neoplasms, particularly low grade. This cell has a nucleated globular body and a cytoplasmic process with a nontapering, flattened, bulbous or fishtail-like end. The cercariform cell corresponds to intermediate cells in histologic and ultrastructural preparations of normal urothelium. The cercariform appearance is the result of pseudostratification of both normal and low-grade neoplastic urothelium. The unique features of cercariform cells make them readily distinguishable from neoplastic squamous cells as well as spindle cells of mesenchymal origin. © 1995 Wiley-Liss, Inc.     

Metastatic upper tract urothelial carcinoma with nest-like features presenting as malignant pleural effusion

Metastatic urothelial carcinoma is a rare cause of pleural effusions. We report a case of urothelial carcinoma of the upper urinary tract in an oldest-old male patient, a smoker, with situs inversus totalis, that presented uniquely with malignant pleural effusion at presentation without evidence of a primary tumor on imaging. Cytological smears of the massive left pleural effusion revealed epithelioid neoplastic cells arranged in short cords, small-to-large clusters, and raspberry-like morules, mimicking mesothelioma; cell block preparations highlighted the presence of tubules and nest-like structures. The tumor cells showed a high nuclear-to-cytoplasmic ratio, nuclear grooves, and mitotic figures. Cytomorphologic features coupled with the immunophenotype of neoplastic cells (p63, GATA3, and uroplakin II positive) allowed the diagnosis of metastatic urothelial carcinoma and a possible nested subtype. These findings were supported by a total body computed tomography (CT) showing no evidence of a mass in the bladder or elsewhere in the urinary tract but a concentric parietal thickening of the proximal left ureter, suggesting malignancy. To our knowledge, a malignant effusion as a primary manifestation of urothelial carcinoma with nest-like features originating in the upper urinary tract has never been described previously. Our case focuses on the value of cell block in the working-up of neoplastic effusions by revealing the architectural pattern of an uncommon malignancy and the correlation between cytopathology and imaging gross findings to reach an accurate diagnosis.     

Extensive psammomatous calcification of the uterus and cervix associated with a uterine serous carcinoma

This report describes a uterine serous carcinoma with bilateral ovarian metastasis, which was associated with widespread extensive psammomatous calcification of the uterine leiomyomata, the myometrium, and the cervical stroma. These psammoma bodies were not associated with tumour or epithelial elements. This psammomatous calcification is rare, with no previous reports of similar cases. The presence of psammoma bodies is probably related to the serous carcinoma, raising the possibility that psammoma body formation in serous carcinomas is the result of a factor secreted locally by the tumour, rather than the widely held theory that their formation is secondary to necrosis, with subsequent dystrophic calcification within a papillary neoplasm.     

Fine‐needle aspiration diagnosis of high grade adenoid cystic carcinoma metastatic to the pancreas

Pancreatic tumors are mostly primary tumors, with only rare metastatic tumors described in the literature. Here we report an unusual case of fine‐needle aspiration (FNA) diagnosis of high grade adenoid cystic carcinoma of the parotid gland metastatic to the pancreas. The aspirate smears were moderately cellular and revealed numerous basaloid neoplastic cells. The cytomorphologic differential diagnosis included primary pancreatic tumor with small cell morphology as well as metastatic tumors. By immunocytochemistry, the tumor cells were positive for cytokeratins (AE1/AE3, CAM5.2, and CK7), and CD117 (C‐KIT), and negative for CD45, WT1, synaptophysin, chromogranin, CD56, TTF‐1, and CK20. The cytomorphologic features and immunoprofile in our case were consistent with high‐grade carcinoma metastases from patient's known salivary gland primary. To the best of our knowledge, this case is the first reported encounter of FNA diagnosis of pancreatic metastasis with small cell morphology from a salivary gland neoplasm as primary site. Diagn. Cytopathol. 2015;43:117–120. © 2014 Wiley Periodicals, Inc.     

Psammoma bodies and optically clear nuclei in bronchiolo-alveolar cell carcinoma. Diagnosis by fine needle aspiration biopsy with histologic and ultrastructural confirmation

The fine needle aspiration cytology of two cases of bronchiolo-alveolar cell carcinoma of the lung having unusual features is reported. One case demonstrated numerous psammoma bodies in the cytologic smears, whereas the other case showed an abundance of cells with optically clear nuclei. Both peripherally located tumors were resected and confirmed as primary bronchiolo-alveolar cell carcinoma by histologic and ultrastructural examination. We believe this to be the first report describing these unusual features of bronchiolo-alveolar cell carcinoma diagnosed by fine needle aspiration cytology. Presented is a discussion of psammoma bodies and optically clear nuclei seen in primary and metastatic tumors of the lung. This will aid in the diagnosis of these cases.     

The “drunken honeycomb” feature of pulmonary mucinous adenocarcinoma: A diagnostic pitfall of bronchial brushing cytology

Pulmonary mucinous adenocarcinoma (PMA) is the terminology recently proposed in the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) International Multidisciplinary Classification of Lung Adenocarcinoma Guidelines for most tumors previously classified as mucinous bronchioloalveolar carcinomas (mBACs). PMA is histologically characterized by lepidic growth and at least some degree of invasive growth of goblet or columnar neoplastic cells with abundant intracytoplasmic mucin. We report here the cytologic features of PMA in a bronchial brushing specimen. The patient is an 84‐year‐old woman with a persistent dense consolidation in the right middle lobe of the lung found on non‐contrast computed tomography (CT) scan. Bronchial brushing smears showed a monotonous population of columnar neoplastic cells forming “drunken honeycomb”‐like cell clusters. The neoplastic cells displayed inconspicuous cytologic atypia. The concurrent transbronchial tissue biopsy and the resection specimen confirmed the diagnosis of PMA. Due to the bland nuclear features, the neoplastic cells in the bronchial brushing specimen were interpreted as benign at the time of the initial diagnosis, demonstrating a diagnostic pitfall of bronchial brushing cytology. A high index of suspicion is recommended when a lung lesion with “drunken honeycomb”‐like cell clusters is encountered in bronchial brushing specimens. The review of the literature regarding the recently designated PMA is presented. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.     

Primary papillary serous neoplasia of the peritoneum: a clinicopathologic and ultrastructural study of eight cases

The well-documented but rare primary papillary serous peritoneal tumors are difficult problems for the pathologist and the clinician. Because of their unusual location, these tumors are often classified as mesothelioma or advanced ovarian carcinoma. In this study, we report the clinicopathologic features of eight primary peritoneal serous papillary tumors and compare their histologic and ultrastructural features to 12 serous ovarian tumors and 16 epithelial mesotheliomas (two peritoneal and 14 pleural). The eight peritoneal serous papillary tumors occurred in women aged 19 to 75 years; two were serous tumors of low malignant potential (borderline) and six were serous carcinomas. The tumors were located in the mesosalpinx, left pelvis, omentum, and/or surface of the ovary. The two patients with borderline neoplasms had long disease-free survival (11 years and 20 years), while three of the four patients with carcinoma with more than 1 year of follow-up died of disease. The peritoneal serous papillary tumors were morphologically identical to serous ovarian tumors of equivalent grade. Well-differentiated papillary structures with distinct fibrovascular cores and one or several layers of columnar, crowded cells, dense overlapping nuclei with a long axis perpendicular to the surface of the papillary cores, and numerous psammoma bodies were features of the peritoneal and ovarian serous tumors. In contrast, the tubulo-alveolar, solid, or poorly defined papillary structures lined by well-spaced polygonal to cuboidal cells with abundant cytoplasm, absence of nuclear polarity, and infrequent psammoma bodies characterized the mesotheliomas. Epithelial mucin and carcinoembryonic antigen (CEA) immunoreactivity, when present, supported a diagnosis of serous tumor in these generally mucin-poor and CEA-negative neoplasms. Ultrastructurally, the cells of serous tumors had slender, straight microvilli of variable length interspersed with or without cilia, while the nonciliated cells of mesothelioma had long, exuberant, wavy microvilli. The morphologic and clinical features of the peritoneal papillary serous tumors are distinctive enough to warrant their separation from mesotheliomas.     

Psammoma bodies in metastatic carcinoma to the thyroid

In a review of the 427 cases of thyroid with malignant neoplasm that were surgically resected at the Cancer Institute Hospital during the 10-yr period from 1978 to 1987, five cases of metastatic carcinoma to the thyroid were found. Psammoma bodies were histologically observed in three of the five cases. Primary thyroid carcinoma was highly suspected in the three cases, because psammoma bodies were detected during preoperative examinations that included image diagnosis and aspiration biopsy cytology. Thus, the presence of psammoma bodies in any kind of thyroid tumor should be carefully evaluated, both clinically and histologically, to ensure that the possibility of metastatic origin is not overlooked.     

Claudin 4 identifies a wide spectrum of epithelial neoplasms and represents a very useful marker for carcinoma versus mesothelioma diagnosis in pleural and peritoneal biopsies and effusions

We evaluated the usefulness of the tight-junction associated protein Claudin 4 (CL-4) in the diagnosis of mesothelioma and mimickers, analyzing biopsies from 454 tumors, including 82 mesotheliomas, 336 carcinomas of different origin (278 primary, 58 metastatic to serosae), 36 nonepithelial spindle cell neoplasms, as well as 97 cytological samples from reactive effusions (12), mesothelioma (23) and metastatic carcinomas (62). CL-4 was consistently negative in normal and reactive mesothelium, as well as in all 82 mesotheliomas. In contrast, strong reactivity was found in 57/58 serosal metastasis, and in 245/278 primary carcinomas, with uppermost expression (150/153) in those most frequently involved in the differential with mesothelioma (lung, breast, gastrointestinal tract, pancreas, ovary, primary serous papillary carcinoma of peritoneum). On effusions, reactive and neoplastic mesothelial cells were regularly negative, while metastatic tumor cells stained positively in 60/62 (96.8%) cases. Among spindle cell neoplasms, only 2/9 biphasic synovial sarcomas and 4/4 follicular dendritic cell sarcomas stained positively. Results indicate that CL-4 reacts with the majority of epithelial neoplasms that often metastasize to serous membranes, representing a pancarcinoma marker with extremely high sensitivity and specificity. CL-4 may be considered a primary immunohistochemical reagent to rule out the diagnosis of mesothelioma.     

Multiple calcifying fibrous tumors of the pleura

Calcifying fibrous tumor (CFT) is a rare lesion characterized histologically by hypocellular hyalinized collagenous tissue with psammomatous and/or dystrophic calcifications and patchy lymphoplasmacytic infiltrates. CFT usually occurs in the somatic soft tissue of children and young adults but is rarely found in the pleura. We describe here an unusual case of multiple small CFTs in the right mediastinal pleura of a 54-year-old man who had a history of renal cell carcinoma. Suspecting pulmonary and pleural metastases, we performed wedge resection of the right middle lobe and local excision of two nodules in the right pleura. Light microscopy revealed metastatic lesions of renal cell carcinoma in the resected wedge. The pleural nodules were well circumscribed and composed of hypocellular, dense, hyalinized, collagenous tissue with scant lymphoplasmacytic infiltration and characteristic psammoma bodies. Immunohistochemical staining revealed that most spindle cells were positive for vimentin, CD34 and factor XIIIa, and negative for epithelial membrane antigen, keratin, smooth-muscle actin, desmin, S-100 protein and anaplastic lymphoma kinase. We made a histological diagnosis of CFT of the pleura, and the patient remains well 6 months after the wedge resection.     

Immunohistochemical detection of cytotoxic lymphocytes in malignant serous effusions.

The use of ancillary techniques to aid in the diagnosis of metastatic carcinoma in serous effusions has been the subject of numerous studies. In this article, we study 35 cases of malignant effusions (metastatic adenocarcinoma) and 20 benign effusions using a panel of immunohistochemical markers to determine whether changes in the subpopulations of accompanying lymphoid cells can be detected with this technique and whether such changes are associated with the presence of malignancy. We noted a significant increase in cytotoxic lymphocytes, defined as the percentage of all lymphoid cells staining with an antibody to TIA-1 (an antigen localized to the cytotoxic granule membranes of cytotoxic T cells and natural killer cells) in malignant compared with benign effusions (23% vs. 12%; P < 0.05). In addition, nearly all cases in which cytotoxic lymphocytes composed > 20% of the lymphoid cell population contained metastatic tumor. Thus, immunohistochemical staining for TIA-1 can reliably detect cytotoxic lymphocytes in cell blocks of serous effusions; in addition, a relative increase in their number is associated with the presence of malignancy.