Squamous cell carcinoma arising in association with verruca vulgares and HPV-2: a clinicopathologic study with p16 and p53 immunohistochemical studies and human papillomavirus in situ hybridization studies.

BACKGROUND: We observed cutaneous squamous cell carcinomas of the skin (SCCS) with histologic features suggesting they are arising in association with verruca vulgares (SCC-VV). We analyzed SCC-VV to determine what types of human papillomaviruses (HPVs) could be detected by in situ hybridization. We also analyzed demographic and clinical features and performed immunohistochemical studies for p53, p16, and Ki-67. MATERIALS AND METHODS: Five cases of SCC-VV were chosen and compared with 5 cases each of cutaneous squamous cell carcinoma with bowenoid features (SCC-BD), and cutaneous squamous cell carcinoma with keratoacanthomatous features (SCC-KA). RESULTS: We identified HPV-2 in 3 of 5 SCC-VV and SCC-KA, and 2 of 5 SCC-BD. SCC-VV showed a decreased amount of p16 immunoexpression compared with the other types, particularly SCC-BD (P=0.0108 ). SCC-KA showed a decreased p53 (P=0.0096) and Ki-67 (P=0.0007) immunoexpression compared with the other types. CONCLUSIONS: SCC-VV seems to occur in older immunocompetent individuals and may be distinguishable from other SCCS types by histologic and immunohistochemical methods. HPV-2 and HPV-1 were the only types of HPV identified in this study, including SCCS with such diverse morphologic appearances as SCC-VV, SCC-BD, and SCC-KA. Further studies are needed to confirm these findings.

Pulmonary nodular lymphoid hyperplasia (pulmonary pseudolymphoma): the significance of increased numbers of IgG4-positive plasma cells.

On the basis of an initial case, we hypothesized that IgG4-positive plasma cells may be increased in pulmonary nodular lymphoid hyperplasia (PNLH) compared with other lymphoid proliferations of the lung. Six cases of PNLH, 9 cases of low-grade B-cell lymphoma of the bronchus-associated lymphoid tissue (BALT), 8 cases of intraparenchymal lymph nodes, 8 cases of either primary or secondary follicular bronchiolitis, and 4 cases of lymphocytic interstitial pneumonitis were stained by immunohistochemical analysis for IgG4 and IgG. The mean number of IgG4-positive and IgG-positive plasma cells and the IgG4/IgG ratio were determined from a manual count of images from 3 separate high-power fields (hpf) of areas showing the highest numbers of stained cells, respectively. The mean number of IgG4-positive plasma cells and the IgG4/IgG ratio were significantly increased in PNLH (IgG4=78/hpf, IgG4/IgG=0.35) compared to low-grade lymphoma of BALT (IgG4=4/hpf, P=0.02; IgG4/IgG=0.03, P=0.005), intraparenchymal lymph nodes (IgG4=7/hpf, P=0.03; IgG4/IgG=0.06, P=0.007), follicular bronchiolitis (IgG4=0/hpf, P=0.02; IgG4/IgG=0, P=0.004), and lymphocytic interstitial pneumonitis (IgG4=2/hpf, P=0.02; IgG4/IgG=0.06, P=0.007). These findings support our current understanding of PNLH as a distinct form of reactive lymphoid proliferation, potentially aid in its distinction from low-grade B-cell lymphoma of BALT, and raise the possibility that PNLH may belong within the family of IgG4-related sclerosing diseases.

Vanishing lung syndrome and HIV infection: an uncommon yet potentially fatal sequela of cigarette smoking.

Persons with HIV infection have a higher risk of infectious pulmonary complications, chronic obstructive pulmonary disease, lung cancer, pulmonary hypertension, and pulmonary fibrosis than individuals not infected with HIV. Herein, we describe the clinical course of a patient with longstanding and well-controlled HIV infection and multiple previous pneumothoraces who presented to medical attention with insidious onset of shortness of breath and was diagnosed with vanishing lung syndrome (VLS). The VLS or giant bullous emphysema is a distinct clinical syndrome characterized by large bullae, predominantly in the upper lobes, occupying at least one third of the hemithorax and compressing surrounding normal lung parenchyma. It is a progressive disorder that typically occurs in young men, the majority of whom are smokers. As people with HIV/AIDS are now surviving well into middle age and beyond, clinicians are more likely to encounter VLS and severe obstructive lung disease, which are potentially fatal but preventable conditions.

Update on nonneoplastic pulmonary lymphoproliferative disorders and related entities.

CONTEXT: Recent discoveries have expanded the spectrum of nonneoplastic pulmonary lymphoproliferative disorders and have provided new insights into their pathogenesis and treatment. OBJECTIVE: To review the thoracic manifestations of immunoglobulin (Ig) G4-related sclerosing disease and summarize current concepts and differential diagnosis of follicular bronchiolitis, lymphocytic interstitial pneumonitis, and nodular lymphoid hyperplasia. DATA SOURCES: Data sources include recent and old articles, cases from the personal files of the author, and cases borrowed with permission from other authors. CONCLUSIONS: Additional studies will be needed to further refine and add to observations in this evolving area of pulmonary pathology.

Pulmonary pathologic findings of fatal 2009 pandemic influenza A/H1N1 viral infections.

CONTEXT: In March 2009, a novel swine-origin influenza A/H1N1 virus was identified. After global spread, the World Health Organization in June declared the first influenza pandemic in 41 years. OBJECTIVE: To describe the clinicopathologic characteristics of 34 people who died following confirmed A/H1N1 infection with emphasis on the pulmonary pathology findings. DESIGN: We reviewed medical records, autopsy reports, microbiologic studies, and microscopic slides of 34 people who died between May 15 and July 9, 2009, and were investigated either by the New York City Office of Chief Medical Examiner (32 deaths) or through the consultation service of a coauthor (2 deaths). RESULTS: Most of the 34 decedents (62%) were between 25 and 49 years old (median, 41.5 years). Tracheitis, bronchiolitis, and diffuse alveolar damage were noted in most cases. Influenza viral antigen was observed most commonly in the epithelium of the tracheobronchial tree but also in alveolar epithelial cells and macrophages. Most cases were reverse transcription-polymerase chain reaction positive for influenza. Histologic and microbiologic autopsy evidence of bacterial pneumonia was detected in 55% of cases. Underlying medical conditions including cardiorespiratory diseases and immunosuppression were present in 91% of cases. Obesity (body mass index, >30) was noted in 72% of adult and adolescent cases. CONCLUSIONS: The pulmonary pathologic findings in fatal disease caused by the novel pandemic influenza virus are similar to findings identified in past pandemics. Superimposed bacterial infections of the respiratory tract were common. Preexisting obesity, cardiorespiratory diseases, and other comorbidities also were prominent findings among the decedents.

Omental roll-up: a technique for islet engraftment in a large animal model.

BACKGROUND: Attrition of transplanted islets is significant after hepatic embolization. This study was designed to investigate a novel surgical technique for islet transplantation into the omentum. This site allows placement of the islets in a three-dimensional (3D) matrix, with growth factors, to temporarily culture the islets in vivo while revascularization progresses. MATERIALS AND METHODS: Five female dogs (three partial and two total pancreatectomies) received an autologous islet transplant in the omentum. Islets were suspended in 1 mL of PBS containing 10 ug of vascular endothelial growth factor (VEGF). Fresh autologous plasma (10 mL) was mixed with the islet/VEGF suspension. The coagulum containing the islets and VEGF was then placed on the greater omentum. The leading edge of omentum was rolled up to secure the islet/VEGF/coagulum in position and to present the thin islet layer with two omental surfaces for implantation. Omentum was recovered at 2, 13, 21, 42, and 180 d. RESULTS: Immunohistochemical staining for synaptophysin, glucagon, and insulin confirmed the presence of transplanted islets in all omenta. Insulin and C peptide production from the omental islets was confirmed in portal venous samples, and normalization of morning glucose levels beginning on day 7 was seen in the total pancreatectomy experiment. CONCLUSIONS: Autologous islets implant in rolled-up omentum when placed as a VEGF/autologous plasma coagulum. This technique has potential benefits, including the opportunity to accelerate revascularization and to investigate local strategies for modulating the immune response.

Primary pleural neoplasia: entities other than diffuse malignant mesothelioma.

CONTEXT: Overwhelmingly, the most common neoplasm involving the pleura is metastatic carcinoma. In contrast, diffuse malignant mesothelioma occurs relatively rarely; however, it is nonetheless the most common neoplasm primary to the pleura. Metastatic carcinoma and diffuse malignant mesothelioma each have their own prognostic and therapeutic characteristics. Other primary pleural neoplasms occur uncommonly or rarely, with their own prognostic and therapeutic characteristics. OBJECTIVE: To review primary pleural neoplasms other than diffuse malignant mesothelioma, to better ensure correct diagnosis and optimal assessment of prognosis and treatment. DATA SOURCES: Literature review and primary material from the authors' institutions. CONCLUSIONS: A nonexhaustive group of uncommon to rare benign and malignant primary pleural neoplasms--other than diffuse malignant mesothelioma--are presented, of which one must be aware in order to maintain an appropriate index of suspicion to include them in the differential diagnosis of a pleural tumor.

AIDS-associated plasmablastic lymphoma presenting as a poorly differentiated esophageal tumor: a diagnostic dilemma.

Plasmablastic lymphoma (PBL) is a rare form of diffuse large B-cell lymphoma characterized by weak/absent expression of conventional B-cell markers and strong expression of plasma cell markers. It is strongly associated with human immunodeficiency virus (HIV) and Epstein Barr virus infection, and shows an unusual tropism to the oral cavity. Herein we describe a patient with AIDS who presented with weight loss and dysphagia owing to a large gastroesophageal mass. His radiographic and endoscopic findings and long history of cigarette consumption suggested carcinoma. Biopsy demonstrated a poorly differentiated tumor stained negatively to routine lymphoid markers including CD20. However, gene rearrangement studies confirmed a B-cell process and a more detailed immunohistochemical analysis revealed the cells stained positively for CD138 (plasma cell antigen). These findings were diagnostic of PBL. Our report reviews the wide differential diagnosis of PBL and underscores the importance of a broad array of viral and molecular studies needed to establish this diagnosis.

Pleuropulmonary pathology of Birt-Hogg-Dubé syndrome.

Birt-Hogg-Dubé (BHD) syndrome is a rare inherited genodermatosis characterized by distinctive cutaneous lesions, an increased risk of renal and colonic neoplasia, and the development of pleuropulmonary blebs and cysts. Although the pathology of renal and cutaneous manifestations of BHD has been well described, few reports have detailed the pathologic features of pulmonary involvement. Herein we present the pathologic findings from biopsies of 2 BHD patients with spontaneous pneumothorax: 1 with known BHD and another clinically suspected to have lymphangioleiomyomatosis. Histologic features included basilar cysts comprised of intraparenchymal collections of air surrounded by normal parenchyma or a thin fibrous wall and blebs consisting of collections of air within the pleura. Although these histologic findings are not specific to BHD, their predominantly basilar location contrasts with the apical distribution of other more well-recognized causes of spontaneous pneumothorax, such as emphysematous bullae and idiopathic blebs. It is important for pathologists to be aware of this rare cause of spontaneous pneumothorax because BHD can radiographically simulate other causes of pulmonary cysts and the lung and pleura may be the initial sites of involvement. Patients with BHD are at increased risk for renal neoplasia and may benefit from periodic surveillance. Pathologists should raise the possibility of BHD in nonapical lung biopsies from young or middle-aged patients that show blebs or cysts.

Fibroepithelial lesions with cellular stroma on breast core needle biopsy: are there predictors of outcome on surgical excision?

Fibroepithelial lesions with cellular stroma (FELCS) in breast core needle biopsy (CNB) specimens may result in either fibroadenoma or phyllodes tumor at excision. We evaluated histologic features, proliferation indices (by Ki-67 and topoisomerase II a immunostaining) and p53 expression in 29 cases of FELCS in CNB specimens and correlated these with excision findings in a blinded manner. On excision, 16 patients had fibroadenomas and 12 had phyllodes tumors. All CNB specimens with mildly increased stromal cellularity were fibroadenomas on excision (n=4), and all with markedly cellular stroma were phyllodes tumors (n=4). Among CNB specimens with moderate cellularity (12 fibroadenomas and 8 phyllodes tumors), only stromal mitoses were discriminatory histologically. Stromal proliferation indices were significantly higher in CNB that were phyllodes tumors vs fibroadenomas. Assessment of stromal cellularity, mitoses, and proliferation indices might help determine the probability of phyllodes tumor occurring and guide management of these cases.

Prognostic implications of molecular and immunohistochemical profiles of the Rb and p53 cell cycle regulatory pathways in primary non-small cell lung carcinoma.

PURPOSE: Many studies have highlighted the aberrant expression and prognostic significance of individual proteins in either the Rb (particularly cyclin D1, p16INK4A, and pRb) or the p53 (p53 and p21Waf1) pathways in non-small cell lung cancer. We hypothesize that cumulative abnormalities within each and between these pathways would have significant prognostic potential regarding survival. EXPERIMENTAL DESIGN: Our study population consisted of 106 consecutive surgically resected cases of predominantly early-stage non-small cell lung cancer from the National Cancer Institute-Mayo Clinic series, and assessment of proteins involved both immunohistochemical (cyclin D1, p21Waf1, pRb, p16INK4A, and p53) and mutational analysis (p53) in relationship to staging and survival. RESULTS: Cyclin D1 overexpression was noted in 48% of the tumors, p16INK4A negative in 53%, pRb negative in 17%, p53 immunopositive in 50%, p53 mutation frequency in 48%, and p21(Waf1) overexpression in 47%, none with prognostic significance. Cyclin D1 overexpression in pRb-negative tumors revealed a significantly worse prognosis with a mean survival of 2.3 years (P = 0.004). A simultaneous p53 mutation dramatically reduced the mean survival time to 0.9 years (P = 0.007). Cyclin D1 overexpression with either a p53 mutation or a p53 overexpression was also associated with a significantly poorer prognosis (P = 0.0033 and 0.0063, respectively). CONCLUSIONS: Some cumulative abnormalities in the Rb and p53 pathways (e.g., cyclin D1 overexpression and p53 mutations) significantly cooperate to predict a poor prognosis; however, the complexity of the cell cycle protein interaction in any given tumor warrants caution in interpreting survival results when specific protein abnormalities are taken in isolation.