A comprehensive review of the "tigroid" background cytological concept: what, when, where and why?

The concept of "tigroid" background is used in cytology to describe a peculiar smear background characterized by the presence of a relatively granular, reticulated material that was described as "foamy, lazy, tiger-striped or astrakhan". It was used to describe the background seen in smears obtained from seminoma. In addition to seminoma, we now know that it can be present in different tumours, mostly carcinomas and round cell sarcomas. These share with seminoma a cytoplasm with high glycogen content and many times clear cell morphology. The "tigroid" background is seen when smears are air-dried and Romanowsky-based stains are used (May-Grunwald-Giemsa and Diff-Quik stains). It is only seen in fine needle aspiration or intraoperative squashing or scrapping samples, but not in specimens obtained from effusions or liquid-based cytology. Wet-fixed cytologic samples with alcohol or with formaldehyde tend to dissolve the background so it is not usually present in Papanicolaou stained smears. In this review, we discuss tumours in which the "tigroid" background is observed and its potential diagnostic utility and aetiology. It is interesting to remark that except for parathyroid adenoma and adenomatoid tumour all the neoplasms in which this background has been observed are malignant.

Fine needle aspiration cytology of polymorphous adenocarcinoma of the salivary glands: A report of 11 patients and review of the literature.

BACKGROUND: Polymorphous adenocarcinoma (PAC) is a rare malignant tumor of the minor salivary glands. It has an infiltrative growth, variable architectural patterns, neurotropism and cellular monomorphism. Approximately 75% of the cases show a specific mutation in the protein kinase D1 (PRKD1) gene. Reflecting the rarity of the tumor and intraoral location, the cytologic experience is limited with few reported series. In this study we analyze our cytologic experience to determine if a preoperative diagnosis is possible. METHODS: A retrospective study of 11 patients with PAC in which a cytologic study was available. A review of the literature was also performed. RESULTS: Our study shows that PAC has relatively constant cytological features. The analysis of the cytological literature although it shows some heterogeneity, also reveals repetitive cytological findings. Smears are cellular with irregular groups some showing pseudopapillary branching morphology. Monolayered clusters and small acinar structures are also present. Most cases have small metachromatic globules embedded within the groups determining a cylindromatous pattern. Tumoral cells are small and uniform with scarce to moderate cytoplasm. Nuclei are round and oval with occasional grooves and small nucleoli. CONCLUSION: PAC has characteristic cytological features that together with its location in minor salivary gland must make us consider it preoperatively. It may resemble basal cell adenoma and epithelial-rich pleomorphic adenoma so we should be cautious in the final diagnosis. Whenever possible, the characteristic cytomorphology of PCA should make us evaluate the mutational status of PRKD1 gene since it may permit a more accurate diagnosis.

Colon Tumor Tattooing-Derived Ink-Laden Macrophages in Peritoneal Ascitic Fluid.

INTRODUCTION: Macrophages containing exogenous pigments are commonly encountered in cytological specimens. CASE PRESENTATION: We present a case of tumor tattooing as an infrequent exogenous source of peritoneal fluid macrophagic pigment in a 76-year-old female. DISCUSSION AND CONCLUSION: Tattooing-derived ink can be a source of macrophagic pigment and should not be confused with other endogenous or exogenous pigments. The anatomical location and past medical history of the patient can aid in the diagnosis.

FNA cytology of postoperative pseudotumoral lesions induced by oxidized cellulose hemostatic agents.

BACKGROUND: The use of topically applied hemostatic substances during surgery has become a common practice. In some cases, the material is not absorbed or induces a granulomatous reaction resulting in a pseudotumoral lesion. With imaging studies, it is not possible to differentiate this from a tumor recurrence or abscess. This study describes the authors' cytologic experience with a large series of pseudotumoral lesions induced by oxidized cellulose, one of the most commonly used hemostatic agents. Almost no cytologic descriptions are available in the medical literature. METHODS: Sixteen patients were evaluated, and the most common sites of fine-needle aspiration (FNA) were the mediastinum and thyroid surgical bed. Other locations were the axilla, neck, vulva, liver, and retroperitoneum. All these lesions appeared after surgical procedures in which oxidized cellulose was used as a topical hemostatic agent. The interval time between surgery and FNA varied from 4 to 46 months with a mean of 15 months. RESULTS: Cytology samples showed very similar findings. In all cases, foreign-body material with a variable granulomatous reaction was present. Oxidized cellulose was seen as laminated inorganic fragments and most often showed an elongated, quadrangular appearance. Amorphous, ill-defined fragments as well as a dense proteinaceous background with phagocytic cells were also present. CONCLUSIONS: The current study demonstrates that FNA cytology is a very useful method for the detection of pseudotumoral lesions induced by hemostatic agents. Pathologists must be familiarized with this finding because cytology permits easy differentiation from tumor recurrence.

Fine needle aspiration cytology of the normal kidney: A cyto-histological and immunocytochemical correlation study.

BACKGROUND: Differentiation between normal renal cellular structures and renal tumors can be a diagnostic challenge during fine needle aspiration. It is of particular relevance during percutaneous thermal ablation because of the small size of tumors and when performing rapid on-site evaluation. METHODS: A cyto-histological correlation study assisted by immunocytochemistry was performed. The study was based on 10 nephrectomy specimens. For the identification of proximal tubular cells we used CD10 and α-methylacyl coenzyme A racemase (AMACR). PAX8 and GATA3 were used for the recognition of distal and collecting duct cells. For a precise correlation representative cytologic groups were photographed before and after immunocytochemistry. RESULTS: All cases showed: (a) glomeruli; (b) presence of at least 2 different epithelial cell populations that distribute separately, one representing the proximal tubule and the other more distal segments; and (c) existence of isolated, laminar basement fragments and slender, intact tubular structures. Proximal tubular cells were large with granular cytoplasm, indistinct cell borders, moderate anisonucleosis, and variable presence of pigment. Their immunophenotype was CD10+, AMACR+, PAX8-, and GATA3-. In all cases, cellular aggregates different of nonproximal tubular cells were present. They were smaller than proximal tubular cells with less cytoplasm, better-defined cell borders and uniform nuclei. Their immunophenotype was CD10-, AMACR-, PAX8+, and GATA3+ CONCLUSION: Aspirates from the normal kidney show characteristic features that permit a specific recognition. Different segments of the tubular system can be specifically recognized avoiding confusion with renal tumors. In difficult cases immunocytochemistry is a very helpful aid.

Micropapillary carcinoma of the urinary tract: a cytologic study of urine and fine-needle aspirate samples.

OBJECTIVE: Micropapillary carcinoma (MPC) is an aggressive variant of urothelial carcinoma that needs early and specific recognition. In order to determine whether this tumor variant can be recognized with cytology, we evaluated a large cytohistological series. STUDY DESIGN: It was a retrospective cytohistological correlation study including 20 patients with MPC. Only those cases in which the tumor exhibited >50% of micropapillary growth were selected. Twenty exfoliative urine specimens and four needle aspirates from lymph node metastases were reviewed. RESULTS: On histology, 14 cases were infiltrative, while 6 were exclusively superficial. Cytology was characterized by numerous small, cohesive groups and single neoplastic cells. Pseudopapillae were present in 17 cases and in 9 they were a relevant finding. Morules were present in 15 cases. Isolated microacini were seen in 14 cases. Infiltrative tumors showed more neoplastic groups. Cellular atypia was prominent in 17 cases. In 15 cases, a cytologic diagnosis of urothelial carcinoma was made. One case was diagnosed as adenocarcinoma. The remaining 4 cases were considered suspicious of malignancy. CONCLUSIONS: The peculiar morphology of MPC of the urinary tract is partially reflected on cytology, allowing in some cases a specific recognition. This is important since the aggressive behavior of this neoplasm needs rapid management and treatment.

Cytologic features of hepatoid carcinoma of the ovary: a case report with immunocytologic evaluation of HepPar1.

BACKGROUND: Hepatoid carcinoma is a rare, primary neoplasm of the ovary characterized by histologic, immunobistochemical and analytical evidence of hepatic differentiation. Reflecting the rarity of this entity, few cytologic descriptions are available. CASE: A 65-year-old woman presented with an abdominopelvic mass, peritoneal implants and elevated levels of CA-125 and a-fetoprotein (AFP). Cytologic examination of the ascitic fluid revealed cellular samples of polygonal cells in trabecular and papillary groups. Neoplastic cells were predominantly monomorphous, but some groups exhibited marked cellular atypia. A few trabecular groups showed peripheral endothelial rimming. Histologically, the neoplasm had evident hepatocellular differentiation, with a solid, trabecular growth of polygonal, eosinophilic cells with well-defined boundaries. The cells were immunoreactive with keratins, AFP and HepPar1. Retrospectively, HepPar1 was tested in cytologic samples, with a positive result. CONCLUSION: As occurs with other hepatocellular neoplasms, the hepatic differentiation that characterizes this unusual neoplasm may not be easily recognizable in effusion samples. However, there are some features that, in addition to an elevated AFP value, may help to suggest the diagnosis. A predominant trabecular arrangement with occasional endothelial rimming and HepPar1 immunoreactivity, consistent with hepatic differentiation, are unusual in common surface epithelial ovarian tumors.

Fine-needle aspiration cytology of large cell neuroendocrine carcinoma of the lung: a cytohistologic correlation study of 11 cases.

BACKGROUND: The classification of pulmonary neuroendocrine neoplasms is particularly controversial. Large cell neuroendocrine carcinoma (LCNEC) has emerged as a separate entity among pulmonary endocrine neoplasms and the criteria for its histologic diagnosis are now well-described. However, cytologic diagnosis presents more difficulties and to the authors' knowledge, few cytologic studies concerning the entity have been published to date. The objective of the current study was to describe the cytologic features of LCNEC in an attempt to distinguish it from other pulmonary carcinomas. METHODS: A cytohistologic study of 11 surgical lobectomy specimens classified as LCNEC was performed. In all these cases, preoperative fine-needle aspiration cytology (FNAC) material was available for review. RESULTS: The cytologic features of the cases were rather similar, resulting in a repetitive pattern. The majority of smears were hypercellular with numerous single, medium-to-large cells. Naked nuclei were abundant but a variable subset of cells demonstrated evident cytoplasm. Groups were 3-dimensional and of variable size, some of them large. Nuclear pleomorphism, molding, and mitosis were common findings. A necrotic background was evident in 6 cases. In 6 cases, neoplastic groups demonstrated peripheral nuclear palisading. Rosette-like structures were present in samples from 5 patients. In 4 cases, immunocytochemistry for the detection of synaptophysin was performed, with positive results. CONCLUSIONS: The authors' experience with 11 FNAC cases of LCNEC, has led them to believe that the cytologic image of LCNEC is peculiar and recognizable in many cases. Nevertheless, it is a difficult diagnosis to make and immunocytochemistry plays a critical diagnostic role.

Cytologic diagnostic accuracy in pleomorphic adenoma of the salivary glands during 2 periods. A comparative analysis.

OBJECTIVE: To determine if previous experience with the cytologic presentation of pleomorphic adenoma (PA) results in a lower number of diagnostic errors. STUDY DESIGN: Comparative analysis of the diagnostic accuracy of PA during 2 periods (1980-1994 and 1995-2003). The first period included 198 tumors and the second, 230. Diagnostic errors were divided into major or minor according to the consequences for patient management. Major errors were considered those that could result in an erroneous surgical approach or treatment delay. RESULTS: Concordant results increased from 88.4% to 91.2%. Sensitivity rose from 92.6% to 95.5%. The false negative rate diminished from 7.1% to 4.5%. Regarding malignancy, false negative diagnoses diminished from 5 to 3. The second period included no false positive diagnoses of malignancy, while the first had 3. A total of 42 errors were present, 6 of them were nonrepresentative cases. Thirteen of the remaining 36 (36.1%) were considered major errors, while 23 (63.9%) were classified as minor errors. Major errors diminished from 8 to 5. The most significant reduction in errors occurred in the category of PA showing cystic transformation. CONCLUSION: Cytologic diagnostic accuracy of PA is high, and major errors may diminish if special attention is paid to some pitfalls. Sampling limitations and interpretive difficulties may prevent differentiation from afew cases of carcinoma ex-PA and adenoid cystic carcinoma (ACC). A few diagnostic errors are difficult to avoid. Small tissue biopsies will not resolve these problems.

Cytologic features of pheochromocytoma and retroperitoneal paraganglioma: a morphologic and immunohistochemical study of 13 cases.

OBJECTIVE: To review the cytologic features and potential pitfalls of pheochromocytoma and retroperitoneal paraganglioma and to evaluate complications of the aspiration procedure and the diagnostic utility of immunocytochemistry. STUDY DESIGN: We reviewed 15 cytologic specimens from 12 patients with 13 tumors (1 bilateral case). Ten were adrenal (pheochromocytomas) and 3 extraadrenal paragangliomas. Eleven specimens were from fine needle aspiration (FNA) procedures that were performed in collaboration with radiologists using 23-25-gauge needles. In 3 patients the cytologic material was obtained during intraoperative diagnosis. Immunocytochemistry was performed on alcohol-fixed smears. RESULTS: Two aspirates were hypocellular, while the remainder were cellular. Cells were distributed singly or formed discohesive groups. When present, cytoplasm was abundant and ill defined. Most cells had an eccentric nucleus and plasmacytoid morphology. Nuclear pleomorphism, binucleation and multinucletaion, naked nuclei and intranuclear preudoinclusions were common findings. In 2 cases a lipid background was seen focally. Evident cytoplasmic immunoexpression of synaptophysin or chromogranin was detected in the 10 cases analyzed. One patient developed a hypertensive episode during the FNA procedure. It was controlled medically without complications. CONCLUSION: When adequate cytologic material is present, the recognition of pheochromocytoma and extraadrenal paraganglioma is possible. Together with morphology, immunocytochemical studies allow a specific preoperative diagnosis. Scarce material can be a source of diagnostic errors. FNA of pheochromocytomas is not necessarily contraindicated. When analytic data are not diagnostic, FNA may follow. Aspiration must be performed in an area equipped with the therapeutic tools necessary to control a pheochromocytoma crisis.

Fine needle aspiration cytology of dedifferentiated acinic cell carcinoma of the parotid gland: a case report.

BACKGROUND: Dedifferentiation of acinic cell carcinoma (ACC) to undifferentiated carcinoma occurs rarely and entails a poor prognosis. Most cases of dedifferentiation occur as recurrences of a previously excised ACC. More rarely the neoplasm presents with areas of well-differentiated ACC coexisting with dedifferentiated ones. CASE: An 85-year-old man presented with 2 nodular areas in the right parotid area. Fine needle aspiration of both nodules was performed. In both cases cytology revealed a double epithelial component in similar proportions. The first one corresponded to cohesive groups of small to intermediate-sized, polygonal cells with round, monomorphic nuclei. They were distributed in small and larger, branching groups with acinic morphology. Intermixed with this population, irregular groups of larger, pleomorphic cells with irregular nuclei, prominent nucleoli and scarce cytoplasm were present. In addition, smears showed an abundant lymphoid background. A cytologic diagnosis of "salivary carcinoma with coexisting areas of acinic cell differentiation and high grade, undifferentiated carcinoma" was given. Histopathology revealed a well-differentiated ACC with areas of high grade undifferentiated carcinoma (dedifferentiated ACC). CONCLUSION: The current case expands the cytomorphologic spectrum of ACC. Cytology may permit the preoperative recognition of dedifferentiation, allowing a more sound therapeutic approach.

Fine needle aspiration of toxoplasmic (Piringer-Kuchinka) lymphadenitis: a cytohistologic correlation study.

OBJECTIVE: To define the cytomorphologic features of toxoplasmic lymphadenitis (TL) and to establish the diagnostic sensitivity and specificity of the cytologic diagnosis. STUDY DESIGN: A cytohistologic correlation study of 11 patients in which a histologic diagnosis of TL was available. These cases were analyzed in a blind study among other cases of nonneoplastic lymphadenopathies. The results of the study are expressed in terms of diagnostic sensitivity and specificity. Although not included in the study, 3 other cases of TL with serologic confirmation were also reviewed. RESULTS: Microgranulomas were a characteristic finding in TL. They consisted of small clusters of epithelioid histiocytes, each with abundant cytoplasm and an eccentric, oval nucleus. Diff-Quik-stained smears had cytoplasm with particularly pale staining and a homogeneous appearance. Most microgranulomas had a monotonous appearance with a few, small lymphocytes accompanying the epithelioid cells. No necrosis, suppurative changes or giant cells were present. Blind examination by 4 reviewers led to a correct diagnosis of TL in 9 of the 11 cases. Eight of the 9 cases were recognized by each of the 4 reviewers. One false positive diagnosis was made by 1 of the reviewers. The sensitivity of the diagnosis was 72.7-81.8% and the specificity 98.8-100%. CONCLUSION: This study showed high sensitivity and specificity for the cytologic diagnosis of TL. Given the appropriate clinical context, the presence of characteristic epithelioid microgranulomas permits a diagnosis of TL. The cytologic diagnosis can be easily confirmed with serologic studies, thereby avoiding biopsy.

Fine-needle aspiration cytology of metastatic nasopharyngeal carcinoma.

Cytological features of nasopharyngeal carcinoma (NPC) were reviewed in an attempt to select cytological criteria that permit a specific recognition of metastases. For this purpose, 54 fine-needle aspiration (FNA) procedures from 43 patients with NPC were analyzed. Thirty-two (59.3%) procedures were performed before the histological diagnosis. In 25 (46.3%) procedures, smears showed many neoplastic single cells, clusters, and abundant lymphoid cells (mixed pattern). A dissociated (single cell) pattern consisting of individual neoplastic and lymphoid cells was seen in 18 (33.3%) cases. Finally, 11 (20.4%) cases showed cohesive epithelial clusters (cohesive pattern) without relevant cellular dissociation or lymphoid cells. Squamous-cell differentiation was seen in three of these cases. Most single neoplastic cells presented as large, pleomorphic naked nuclei. Other interesting findings were granulomas (n = 3), prominent eosinophilic infiltrates (n = 4), and suppurative changes (n = 5). In most smears with mixed and dissociated patterns, a nasopharyngeal origin could be suggested. On the contrary, those smears with a cohesive pattern were indistinguishable from other head and neck carcinomas. The presence (on cervical lymph nodes) of a dissociated or mixed (single cells and groups) architectural pattern of large, anaplastic cells and naked nuclei accompanied by an abundant lymphoid component is highly suggestive of undifferentiated NPC. Cytology offers a rapid diagnosis, establishes the necessity of a complete cavum examination, and helps in avoiding unnecessary and harmful biopsies.

Fine-needle aspiration cytology of lipoblastoma: a report of two cases.

Lipoblastoma is an uncommon lipomatous tumor that typically occurs in infants and children. It may present as a single subcutaneous nodule or with multiple lesions (lipoblastomatosis). We describe fine-needle aspiration (FNA) cytologic features of two cases that presented as a subcutaneous lump in the scapular area and as a deeply located mass in the left arm. Smears showed fragments of adipose tissue that consisted of numerous vacuolated adipocytes with few stroma. Nuclei were small and located centrically, without indentations. Myxoid stromal material was a remarkable finding in one case. Both cases showed small delicate vessels, mainly in relation with the myxoid material. No necrosis, atypia, or mitotic figures were present. Cytologic features were characteristic enough to permit a specific diagnosis (adipose tumor suggestive of lipoblastoma). The differential diagnosis should consider lipoma with regressive changes, well-differentiated and mixoid liposarcoma. In addition to cytologic features, the patient's age is very useful for differentiation.

Fine needle aspiration cytology of endocrine neoplasms of the pancreas. Morphologic and immunocytochemical findings in 20 cases.

OBJECTIVE: To analyze the role of fine needle aspiration (FNA) cytology in the preoperative diagnosis of pancreatic endocrine neoplasms. METHODS: Cytologic and histologic diagnoses of pancreatic endocrine tumors were reviewed. A total of 20 FNA cytologic procedures from 20 patients were selected. A false positive case, a retroperitoneal paraganglioma, was also reviewed. Two groups of patients were established: (1) those in whom a surgical biopsy with an immunohistochemical study was available (n = 13), and (2) those with a pancreatic tumor in which the diagnosis was confirmed by immunocytochemical studies (n = 7). In 13 cases the pancreatic tumor was aspirated, while in 7, liver metastases were studied. The immunoexpression of chromogranin and synaptophysin was evaluated in alcohol-fixed smears from 12 and 11 cases, respectively. RESULTS: One false negative and 1 false positive diagnosis were present. In the remaining 19 cases a cytologic diagnosis of pancreatic endocrine tumor was given. Main cytologic features were: (1) a prominent cellular dissociation with many single cells and small, poorly cohesive groups; (2) intermediate to large size cells with ill-defined cytoplasm, naked or eccentric nuclei, and frequent binucleation; and (3) variable nuclear pleomorphism with the characteristic finely granular distribution of the chromatin. Immunocytochemical evidence of endocrine differentiation (chromogranin or synaptophysin) was present in the 12 cases analyzed. CONCLUSION: FNA cytology offers the possibility of a precise preoperative, noninvasive diagnosis of pancreatic endocrine tumors. Cytologic features differ considerably from those of pancreatic adenocarcinoma, allowing differentiation from nonfunctioning endocrine neoplasms. In difficult cases immunocytologic studies are very helpful.

Cytologic features of clear cell carcinoma of the female genital tract. Diagnostic value of the "raspberry body" in nonexfoliative cytologic specimens.

OBJECTIVE: To evaluate the presence of basement membrane stromal material in fine needle aspiration (FNA) and scrape cytologic specimens from patients with clear cell carcinoma (CCC) of the female genital tract. STUDY DESIGN: The study group consisted of 6 patients with CCC (5 ovarian and 1 cervical). Four samples corresponded to FNA specimens and 3 to scrape material obtained during intraoperative consultation for ovarian tumors. FNA was performed on a pelvic recurrence and on liver, pulmonary and lymph node metastases. The 6 cases had a complete histopathologic study. RESULTS: In addition to large, clear cells, all cases showed basement membrane stromal material that assumed several forms. The most common was globular, hyaline structures, either naked or surrounded by neoplastic epithelial cells ("raspberry bodies"). Other fragments were larger, with several spherules and elongated prolongations. Scrape material showed stromal material resembling reduplicated basement membrane material. In Diff-Quik-stained smears (QCA, Tarragana, Spain) it showed metachromatic staining with a pink to purple color. Its recognition on Papanicolaou-stained smears was more difficult since it did not stain or was gray. CONCLUSION: Basement membrane stromal material and, more precisely, "raspberry bodies," are a characteristic cytologic feature of CCC of the female genital tract. The combination of clear, atypical cells and basement membrane stroma is highly specific to this neoplasm and can be observed not only in exfoliative specimens but also in FNA and scrape samples.

Cytologic features of round cell liposarcoma: a report on five patients.

BACKGROUND: Round cell liposarcoma (RCL) and myxoid liposarcoma are now considered as a single pathologic entity for several reasons. Despite many similarities, both morphologic phenotypes may differ considerably, and RCL may be difficult to recognize as liposarcoma. In addition, few cytologic reports describing features of RCL are available. METHODS: Five patients with RCL for whom cytologic study of the tumor was available were reviewed. Only tumors in which round cell or poorly differentiated, hypercellular areas comprised > 75% of the tumor were considered RCL. RESULTS: Smears were hypercellular and consisted of single, round cells with scarce cytoplasm and naked nuclei. Some cells showed slightly oval rather than round nuclei. In three tumors, the background was vacuolated; and, in two tumors, intracytoplasmic vacuoles were present. Isolated fragments of myxoid stroma containing neoplastic cells were identified in two tumors. Pleomorphism was not a prominent finding. CONCLUSIONS: RCL may show morphologic features that are uncommon for a conventional liposarcoma, leading to an erroneous cytologic interpretation. This variant of liposarcoma must be considered when evaluating round cell neoplasms, mainly in adult patients. The presence of oval cells, vacuoles (intracytoplasmic or extracellular), and myxoid stroma should raise this diagnostic possibility, avoiding confusion with other well-known round cell neoplasms.