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.     

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.     

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.     

Relaxase DNA Binding and Cleavage Are Two Distinguishable Steps in Conjugative DNA Processing That Involve Different Sequence Elements of the nic Site

TrwC, the relaxase of plasmid R388, catalyzes a series of concerted DNA cleavage and strand transfer reactions on a specific site (nic) of its origin of transfer (oriT). nic contains the cleavage site and an adjacent inverted repeat (IR₂). Mutation analysis in the nic region indicated that recognition of the IR₂ proximal arm and the nucleotides located between IR₂ and the cleavage site were essential for supercoiled DNA processing, as judged either by in vitro nic cleavage or by mobilization of a plasmid containing oriT. Formation of the IR₂ cruciform and recognition of the distal IR₂ arm and loop were not necessary for these reactions to take place. On the other hand, IR₂ was not involved in TrwC single-stranded DNA processing in vitro. For single-stranded DNA nic cleavage, TrwC recognized a sequence embracing six nucleotides upstream of the cleavage site and two nucleotides downstream. This suggests that TrwC DNA binding and cleavage are two distinguishable steps in conjugative DNA processing and that different sequence elements are recognized by TrwC in each step. IR₂-proximal arm recognition was crucial for the initial supercoiled DNA binding. Subsequent recognition of the adjacent single-stranded DNA binding site was required to position the cleavage site in the active center of the protein so that the nic cleavage reaction could take place.     

Heterocyclic analogues of squamocin as inhibitors of mitochondrial complex I. On the role of the terminal lactone of annonaceous acetogenins

Heterocyclic analogues of squamocin have been semisynthesized by condensation reactions between squamocin-derived alpha-keto esters and heterodinucleophiles. The strong complex I inhibitory potency of squamocin-benzimidazole, a hybrid derivative, illustrates for the first time the functional analogy existing between the terminal butenolide of annonaceous acetogenins and heteroaromatic substructures of classic inhibitors of the enzyme. This finding supports the categorization of this atypical group of inhibitors as antagonists of the ubiquinone substrates. In addition, competition experiments of squamocin-benzimidazole versus squamocin and rolliniastatin-2 suggest that the binding of this hybrid inhibitor is responsible for a negative allosteric effect at the level of the first ubiquinone-binding site (A site) of mitochondrial complex I. This result supports the existence of a large cooperatively regulated inhibitor/ubiquinone-binding pocket located within the catalytic core of the enzyme, consisting of the association of the previously defined affinity sites A and B.