Faculty Bibliography

We studied the staining patterns of bronchioloalveolar carcinoma (BAC) with antibodies to cytokeratin (CK) 7, CK20, and thyroid transcription factor-1 (TTF-1) to determine the diagnostic usefulness of this panel in differentiating BAC from metastatic adenocarcinoma in material obtained by fine-needle aspiration biopsy (FNAB) of the lung. We identified 16 cases of BAC. Of these, 6 were mucinous, 4 were nonmucinous, and 6 were mixed with focal mucinous differentiation. Immunohistochemical analysis with antibodies to CK7, CK20, and TTF-1 was performed on cell-block sections. Of the 6 mucinous BACs, 4 (67%) were CK7+, CK20+, and TTF-1-. All 4 nonmucinous BACs were CK7+ and CK20-, and 2 (50%) were TTF-1+. All 6 mixed BACs were diffusely positive for CK7 and focally positive for CK20; 5 (83%) were TTF-1+. Nonmucinous BACs display CK7, CK20, and TTF-1 immunoreactivity similar to conventional pulmonary adenocarcinoma. Mucinous and mixed BACs have an immunohistochemical phenotype that is different from that of conventional pulmonary adenocarcinoma. Knowledge of these staining patterns is crucial for distinguishing mucinous and mixed BACs from metastatic adenocarcinoma involving the lungs

OBJECTIVE: To study the cytologic features of the oncocytic variant of papillary adenocarcinoma of the thyroid gland to distinguish this subtype from other oncocytic lesions of the thyroid. STUDY DESIGN: We reviewed the smears from aspiration biopsies of 6 proven cases of oncocytic variant of papillary adenocarcinoma and compared their cytologic features with smears from 19 oncocytic follicular neoplasms (11 adenocarcinomas and 8 adenomas). Smears were stained with a modified Giemsa stain (Diff-Quik). RESULTS: All smears were cellular. Colloid was variable but more abundant in cases of the oncocytic variant of papillary adenocarcinoma. The cells in papillary adenocarcinoma had round to ovoid, overlapped nuclei; prominent intranuclear inclusions; and 'grooves.' Nucleoli were generally absent. In oncocytic follicular neoplasms, the cells had round nuclei and prominent nucleoli. Nuclear inclusions and grooves were seen but were not as prevalent as in papillary adenocarcinomas. CONCLUSION: The oncocytic variant of papillary adenocarcinoma of the thyroid gland can be distinguished from other oncocytic lesions by fine needle aspiration biopsy, whereas the absence of prominent nucleoli in oncocytes favors the diagnosis of an oncocytic papillary adenocarcinoma

Despite the efforts for control and eradication of tuberculosis, new cases of the disease are diagnosed daily. The diagnosis of tuberculosis is easily made when the classical features of pulmonary necrotizing granulomatous inflammation are seen. However, extrapulmonary lesions may clinically and radiographically mimic a neoplastic process, and this may lead to misdiagnosis and delay in treatment. We studied 6 patients by aspiration biopsy, all recent immigrants and immunocompetent, who presented with weight loss and fatigue. Of these, 5 patients had a mass. One patient presented with a lytic lesion of bone. In all cases the clinical diagnosis was neoplasia. In all aspirates, the smears showed necrotic debris with neutrophils. No neoplastic cells or granulomas were seen. All cases were signed out descriptively with no specific diagnosis. A search for acid-fast organisms leading to the correct diagnosis of tuberculosis was prompted by clinical investigations that revealed pulmonary lesions, or by repeat aspiration biopsy, which showed granulomatous inflammation. Tuberculosis when present in atypical forms is still a challenging diagnosis. The finding of necrotic debris in a needle biopsy without the clinical signs of an abscess should prompt a search for acid-fast bacilli, since the correct diagnosis will eliminate a needless surgical procedure and will lead to timely and appropriate therapy

Protective immunity against pulmonary tuberculosis (TB) is characterized by the formation in the lungs of granulomas consisting of macrophages and activated T cells producing tumor necrosis factor alpha and gamma interferon, both required for the activation of the phagocytes. In 90% of immunocompetent humans, this response controls the infection. To understand why immunity fails in the other 10%, we studied the lungs of six patients who underwent surgery for incurable TB. Histologic examination of different lung lesions revealed heterogeneous morphology and distribution of acid-fast bacilli; only at the surface of cavities, i.e., in granulomas with a patent connection to the airways, were there numerous bacilli. The mutation profile of the isolates suggested that a single founder strain of Mycobacterium tuberculosis may undergo genetic changes during treatment, leading to acquisition of additional drug resistance independently in discrete physical locales. Additional drug resistance was preferentially observed at the cavity surface. Cytokine gene expression revealed that failure to control the bacilli was not associated with a generalized suppression of cellular immunity, since cytokine mRNA was up regulated in all lesions tested. Rather, a selective absence of CD4(+) and CD8(+) T cells was noted at the luminal surface of the cavity, preventing direct T-cell-macrophage interactions at this site, probably allowing luminal phagocytes to remain permissive for bacillary growth. In contrast, in the perinecrotic zone of the granulomas, the two cell types colocalized and bacillary numbers were substantially lower, suggesting that in this microenvironment an efficient bacteriostatic or bactericidal phagocyte population was generated

In established Leishmania donovani visceral infection in normal mice, anti-interleukin (IL)-10 receptor (IL-10R) monoclonal antibody (MAb) treatment induced intracellular parasite killing within liver macrophages. IL-10R blockade maintained IL-12 protein 40, markedly increased interferon (IFN)-gamma serum levels, and enhanced tissue inducible nitric oxide synthase (iNOS) expression and granuloma assembly. Optimal MAb-induced killing, including synergism with antimony chemotherapy, required endogenous IL-12 and/or IFN-gamma and at least one IFN-gamma-regulated macrophage mechanism-iNOS or phagocyte oxidase. However, in IFN-gamma knockout mice, anti-IL-10R also induced both granuloma formation and leishmanistatic activity. As judged by IL-10R blockade, endogenous IL-10 primarily regulates killing in L. donovani infection by suppressing production of and responses to the Th1 cell-type cytokines, IL-12, and IFN-gamma. However, because anti-IL-10R also released IFN-gamma-independent effects, IL-10 appears to act more broadly and suppresses multiple antileishmanial mechanisms.

We reviewed 43 fine-needle aspiration biopsy (FNAB) smears with abundant extracellular mucinous material to determine whether accurate classification of mucinous lesions is achievable on FN 26 had carcinoma (pure colloid carcinoma [CCA], 23; mixed CCA/invasive ductal carcinoma [IDC], 3); 17 had benign lesions on follow-up (benign MLL, 6; fibrocystic change [FCC], 6; myxoid fibroadenoma [MFA], 5). All carcinomas were identified correctly as malignant on FNAB. The initial cytologic diagnoses in benign cases were benign in 8, atypical in 8, and 'suspicious' for carcinoma in 1. CCAs were moderate to markedly cellular with mild to moderate atypia and lacked oval bare nuclei. Marked nuclear atypia was confined predominantly to cases with mixed CCA/IDC. A distinct feature of CCA was thin-walled capillaries. FCCs and benign MLLs had overlapping cytologic features and showed variable cellularity and no or mild atypia. MFAs were markedly cellular with dyscohesion and variable atypia; stromal fragments and oval bare nuclei were present in every case. Mucinous lesions can be divided into 2 categories by FN those that are adenocarcinomas and those that are not. CCAs have distinctive features that allow a definitive diagnosis on FNAB. Unnecessary surgery can be avoided in MFA by careful evaluation of smear characteristics. Cytologic features of FCC and MLL overlap. Owing to the documented association of MLL with carcinoma, we recommend that lesions that cannot be classified definitively as adenocarcinoma or MFA be considered for conservative excision, even in the absence of atypia