Faculty Bibliography

Short and long-term pulmonary response to inhaled nickel hydroxide nanoparticles (nano-Ni(OH)(2), CMD = 40 nm) in C57BL/6 mice was assessed using a whole body exposure system. For short-term studies mice were exposed for 4 h to nominal concentrations of 100, 500, and 1000 mg/m(3). For long-term studies mice were exposed for 5 h/d, 5 d/w, for up to 5 months (m) to a nominal concentration of 100 mg/m(3). Particle morphology, size distribution, chemical composition, solubility, and intrinsic oxidative capacity were determined. Markers of lung injury and inflammation in bronchoalveolar lavage fluid (BALF); histopathology; and lung tissue elemental nickel content and mRNA changes in macrophage inflammatory protein-2 (Mip-2), chemokine ligand 2 (Ccl2), interleukin 1-alpha (Il-1alpha), and tumor necrosis factor-alpha (Tnf-alpha) were assessed. Dose-related changes in BALF analyses were observed 24 h after short-term studies while significant changes were noted after 3 m and/or 5 m of exposure (24 h). Nickel content was detected in lung tissue, Ccl2 was most pronouncedly expressed, and histological changes were noted after 5 m of exposure. Collectively, data illustrates nano-Ni(OH)(2) can induce inflammatory responses in C57BL/6 mice

The most recent WHO classification of lung cancer defines bronchioloalveolar carcinoma (BAC) as a noninvasive carcinoma or adenocarcinoma in situ. However, the use of this terminology is not uniform and does not reflect standardized criteria. As a result, the diagnosis of BAC has been used in association with small, solitary, and well-differentiated adenocarcinoma as well as tumors with advanced clinical stage. At present, there is a growing consensus among specialists in thoracic oncology that BAC or adenocarcinoma in situ is a rare tumor, and the term should be restricted to adenocarcinomas that show a pure lepidic pattern of growth. The amount of invasive component present in a tumor with a predominant lepidic growth pattern has also been under intense scrutiny. The concept of minimally invasive adenocarcinoma is developing in order to differentiate a pure BAC from an invasive adenocarcinoma that still carries an excellent prognosis.

Our objective was to describe the clinicopathologic features of epithelioid trophoblastic tumors (ETTs) in a series of patients who presented with elevated beta-human chorionic gonadotrophin (hCG) levels and extrauterine lesions resembling primary lung carcinomas. Clinical and pathologic materials were reviewed and Shih and Kurman's diagnostic criteria were applied. Three parous women (38, 49, and 34 y of age) with elevated beta-hCG levels had nondiagnostic gynecologic evaluations, including negative dilation and curettage specimens. Imaging revealed isolated pulmonary lesions, 2 to 8.5 cm in size, resembling primary lung carcinomas. Two patients received multiagent chemotherapy consisting of etoposide, methotrexate, dactinomycin, alternating with cisplatin and etoposide, and all underwent pulmonary resection. Histologically, the cytologic features, epithelioid growth pattern, and hyaline-like material simulated the appearance of nonsmall cell lung carcinoma, but overall, the histologic features along with the immunophenotype supported classification as ETT. Follow-up hysterectomy specimens were histologically normal. All 3 patients are alive and well. The rarity of ETT and its resemblance to squamous and pleomorphic carcinomas of lung have led to diagnostic difficulties. When reproductive-age women present with elevated beta-hCG levels, a pulmonary lesion, and no apparent intrauterine disease, primary pulmonary ETT should be considered. Correlating clinical indices with specific morphologic and immunohistochemical features can ensure diagnostic accuracy and appropriate treatment for favorable outcomes.

Micropapillary adenocarcinoma is associated with poor-prognosis in several organs including the lung. The presence of small tight balls of neoplastic cells devoid of fibrovascular core in cytological preparations (micropapillary tufts) has been described as characteristic of micropapillary adenocarcinoma. In the lung, however, this criterion has not been validated. The cytological material of 46 cases of histologically proven pulmonary adenocarcinoma with a micropapillary component was compared to 33 cases with no micropapillary component to determine the specificity of micropapillary tufts for the histologic diagnosis of micropapillary adenocarcinoma. Other histologic patterns of invasive pulmonary adenocarcinomas (acinar, papillary, and solid) were also compared with patterns of neoplastic cell aggregates in cytological preparations. There were no significant differences in the distribution of micropapillary clusters between the two groups. The positive predictive value for the cytologic diagnosis of a micropapillary component in lung adenocarcinomas was of 64%. Similar findings were observed for other invasive patterns. Therefore, the detection of micropapillary tufts in cytology is not specific for the diagnosis of a pulmonary micropapillary adenocarcinoma in the lung.

BACKGROUND: Radical trachelectomy is a surgical procedure intended to preserve fertility in patients with early-stage cervical carcinoma in which the cervix is amputated in continuity with the parametrium and upper vagina, thereby sparing the uterus and adnexa. Follow-up is performed with periodic cytology specimens. The objective of the current study was to analyze the cytologic findings after this novel procedure. METHODS: Isthmic and vaginal Papanicolaou-stained ThinPrep cytology specimens taken from patients after radical vaginal and abdominal trachelectomy were reviewed. The specimens were also analyzed for the presence of benign endocervical cells, lower uterine segment glandular cells, endometrial stromal cells, and endometrial cells. The findings were correlated with the original diagnosis and follow-up, which included subsequent cytology specimens and biopsies. RESULTS: Cytology specimens (n = 223) from 44 patients were included in this study. An endometrial component was identified in 131 of the cases (59%). Twenty-eight cases were diagnosed as abnormal in the original cytology examination. Twenty of these cases and 5 additional cases that were diagnosed cytologically as benign had subsequent biopsies. The biopsies confirmed the presence of a lesion in only 4 of 25 biopsies (3 low-grade squamous intraepithelial lesions and 1 adenosquamous carcinoma). All cases diagnosed as atypical glandular cells represented tubal metaplasia, lower uterine segment glandular cells, or endometrial stromal cells. CONCLUSIONS: Cytology specimens after trachelectomy frequently contain glandular cells from the lower uterine segment epithelium or endometrial stromal cells, which can lead to a misdiagnosis of atypical glandular cells of undetermined significance. Tubal metaplasia is also a potential pitfall in these specimens. Pathologists and gynecologic oncologists should be aware of the potential pitfalls in the surveillance of smears after trachelectomy.

Fine needle aspiration (FNA) of the spleen is rarely performed, due to fear of procedure complications. The objective of this study is to review the cytologic diagnoses of aspiration biopsy of the spleen performed in a cancer center.Archival material (9-year period) was reviewed and correlated with histologic and ancillary test results, when available.Forty-one splenic FNA specimens were identified. There were no reported procedure complications. Nineteen cases were diagnosed as malignant. Of these, 11 were lymphomas. Nineteen cases were diagnosed as benign. There was one false-negative case and four false-positive cases. Primary splenic neoplasms were rare and misinterpreted as malignant.It is important to be familiar with the normal cytology of this uncommonly aspirated organ in order to successfully identify neoplastic and malignant processes. The use of ancillary studies is important in the definitive classification of benign and malignant splenic lesions

Bone marrow-derived stem cells have been shown to participate in solid organ repair after tissue injury. Animal models suggest that epithelial malignancies may arise as aberrant stem cell differentiation during tissue repair. We hypothesized that if bone marrow stem cells participate in human neoplasia, then solid organ cancers developing after allogeneic bone marrow transplantation (ABMT) might include malignant cells of donor origin. We identified four male patients who developed solid organ cancers (lung adenocarcinoma, laryngeal squamous cell carcinoma, glioblastoma, and Kaposi sarcoma) after myeloablation, total body irradiation, and ABMT from female donors. Donor-derived malignant cells comprised 2.5%-6% of the tumor cellularity The presence of donor-derived malignant cells in solid organ cancers suggests that human bone marrow-derived stem cells have a role in solid organ cancer's carcinogenesis. However, the nature of this role is yet to be defined

To investigate the effectiveness of passive antibody treatment as post-exposure therapy for ricin, we had developed an oropharyngeal aspiration model for ricin lethal challenge and antibody administration. When polyclonal anti-deglycosylated ricin A-chain antibody (dgA Ab) was administered between 1-18 hr after ricin challenge, all animals survived while delayed treatment to 24 hr resulted in 30% survival. The protective effects of dgA Ab correlated with inhibition of apoptosis in the lungs in vivo and in RAW264.7 macrophage and Jurkat T cells in vitro. In addition, ricin-induced cell cytotoxicity was inhibited by both dgA Ab and RAC18 monoclonal antibody against ricin A-chain. Administration of RAC18 monoclonal antibody at 4, 18, and 24 hr after ricin exposure resulted in 100%, 60% and 50% protection, respectively, suggesting that the therapeutic window for passive vaccination extended to at least 24 hr post-ricin lung challenge