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Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm that most commonly involves the visceral or parietal pleura, but that has also been described arising from virtually all organs. This neoplasm exhibits rich vascularity, a characteristic it shares with renal cell carcinoma, making these tumors especially suitable for harboring metastases. We present a case of a 64-year-old woman with history of right breast cancer treated six years previously and who presents with a left pulmonary SFT containing metastatic invasive ductal breast carcinoma as well as a synchronous contralateral primary adenocarcinoma of the lung. The literature on tumor-to-tumor metastasis is then reviewed.

Background Daclizumab is a humanized monoclonal antibody that blocks CD25, the high affinity alpha subunit of the interleukin-2 receptor. Daclizumab therapy targets T regulatory cell and activated effector T cell proliferation to suppress autoimmune disease activity, in inflammatory conditions like relapsing and remitting multiple sclerosis. Here, we present the first report of agranulocytosis with daclizumab therapy in a patient with relapsing and remitting multiple sclerosis. Case presentation Our patient was a 24-year-old Australian female with a clinical history of atopy, lymphocytic enteritis complicated by B12 deficiency, relapsing and remitting multiple sclerosis, recurrent lower respiratory tract infections, vulval/cervical intraepithelial neoplasia and melanoma. She was commenced on daclizumab therapy after failing several lines of treatment for relapsing and remitting multiple sclerosis. During a hospital admission for lymphocytic enteritis, she was incidentally diagnosed with combined immunodeficiency with hypogammaglobulinaemia and declined proposed regular intravenous immunoglobulin infusions. Following six months of daclizumab therapy, our patient presented to hospital with febrile neutropenia. No clear infective cause was found, despite numerous investigations. However, bone marrow biopsy revealed agranulocytosis with an apparent maturation block at the myeloblasts stage. Neustrophil recovery occurred following cessation of daclizumab and the initiation of T cell immunosuppressive agents including systemic corticosteroids and methotrexate. The patient was further investigated for combined immunodeficiency and whole exome sequencing revealed a novel heterozygous missense variant in cytotoxic T lymphocyte antigen 4 (CTLA4), leading to a diagnosis of CTLA-4 haploinsufficiency with autoimmune infiltration (CHAI). Conclusion This case demonstrates that autoimmune disease may be the presenting feature of primary immunodeficiency and should be appropriately investigated prior to the commencement of immunotherapy. Genetic clarification of underlying primary immunodeficiency may provide critical clinical information that alters the safety of the proposed treatment strategy.

Microdissection is a useful method in tissue sampling prior to molecular testing. Tumor heterogeneity imposes new challenges for tissue sampling. Different microdissecting methods have been employed in face of such challenge. We improved our microdissection method by separately microdissecting the morphologically different tumor components. This improvement helped the pyrosequencing data analysis of two specimens. One specimen consisted of both adenocarcinoma and neuroendocrine components. When both tumor components were sequenced together for KRAS (Kirsten rat sarcoma viral oncogene homolog) gene mutations, the resulting pyrogram indicated that it was not a wild type, suggesting that it contained KRAS mutation. However, the pyrogram did not match any KRAS mutations and a conclusion could not be reached. After microdissecting and testing the adenocarcinoma and neuroendocrine components separately, it was found that the adenocarcinoma was positive for KRAS G12C mutation and the neuroendocrine component was positive for KRAS G12D mutation. The second specimen consisted of two morphologically different tumor nodules. When microdissected and sequenced separately, one nodule was positive for BRAF (v-raf murine sarcoma viral oncogene homolog B1) V600E and the other nodule was wild type at the BRAF codon 600. These examples demonstrate that it is necessary to microdissect morphologically different tumor components for pyrosequencing.

Background Intraoperative pathologic diagnosis of bone and soft tissue lesions is an important yet challenging tool in clinical musculoskeletal oncology practice. There is limited information in the literature addressing the practical issues commonly encountered regarding intraoperative frozen section of musculoskeletal lesions. Methods A literature review and retrospective review of practical experience in intraoperative pathology consultation at our institute's sarcoma program were conducted to investigate the pitfalls and limitations of frozen section and potential solutions to overcome these problems. Results Frozen section evaluation is an essential and reliable procedure for guiding intraoperative decisions. Intraoperative cytology as an adjunct to frozen section enhances the accuracy of diagnosis of bone and soft tissue lesions. Cytology can accurately diagnose certain entities alone and is superior to frozen section for certain tumor types and for evaluating bone marrow margins. It is also invaluable in triaging cases for ancillary studies and for tumor banking. Practical working protocols can be developed to optimize the usefulness of intraoperative pathologic consultation. Conclusions Intraoperative pathology consultation should be done in an interdisciplinary approach by correlating clinical, radiologic, and pathologic information. As an adjunct to frozen section, cytology and gross examination enhance the accuracy of diagnosis of musculoskeletal lesions.

Proteins of the nucleotide excision repair pathway repair DNA damage. The excision repair cross-complementing (ERCC) gene family reduces damage to DNA by nucleotide excision and repair. Impaired nuclear excision repair could lead to increased genomic instability that in turn could lead to a more malignant phenotypic behavior of tumors. We therefore evaluated the effect of intratumoral ERCC1 expression on survival in non-small cell lung cancer (NSCLC) patients who underwent surgical resection for cure.Resected tumor and the corresponding normal lung specimens from 51 patients with NSCLC who underwent surgical resection were immediately frozen in liquid nitrogen. Total RNA was extracted, reverse transcribed, and amplified with intron-spanning primers. Quantitation for ERCC1 was done using the Taqman procedure, and gene expression was normalized using 18SrRNA expression as internal reference with ERCC1 levels expressed a unit-less ratio.Tumoral ERCC1 expression ranged from 4.96 to 2,008, with a median value of 54.76. Using an ERCC1 value of 50 to dichotomize the cohort, there was a statistically significant difference in median survival for patients with ERCC1 expression50 (94.6 months) compared to50 (35.5 months) [p = 0.01]. Multivariate analysis revealed that high ERCC1 expression independently predicted for longer survival. There were no significant correlations between ERCC1 expression in tumor tissue and normal lung.We conclude that resected NSCLC patients with high ERCC1 expression (50) have a better survival when compared to patients with low ERCC1 expression (50). We postulate that an intact DNA repair mechanism may reduce the accumulation of genetic aberrations that are thought to contribute to a tumors malignant potential and therefore the risk of relapse after definitive treatment. Future adjuvant and neoadjuvant chemotherapy trials in NSCLC could stratify patients according to their ERCC1 expression levels.

Introduction Sarcoidosis is an incurable, chronic granulomatous disease primarily involving the lungs and lymph nodes of unknown aetiology, treated with non-specific anti-inflammatory/immunosuppressive drugs. Persistently symptomatic patients worsen with a disabling, potentially fatal clinical course. To determine a possible infectious cause, we correlated in a case-control study the clinical information with the presence of bacterial DNA in sarcoidosis mediastinal lymph nodes compared with control lymph nodes resected during cancer surgery. Methods We retrospectively studied formalin-fixed, paraffin-embedded, mediastinal lymph nodes from 30 patients with sarcoidosis and 30 control patients with lung cancer. Nucleic acids were extracted from nodes, evaluated by ribosomal RNA PCR for bacterial 16S ribosomal DNA and the results were sequenced and compared with a bacterial sequence library. Clinical information was correlated. Results 11/30 (36.7%) of lymph nodes from patients with sarcoidosis had detectable bacterial DNA, significantly more than control patient lymph nodes (2/30, 6.7%), p=0.00516. At presentation, 19/30 (63.3%) patients with sarcoidosis were symptomatic including all patients with detectable bacterial DNA. Radiographically, there were 18 stage I and 12 stage II patients. All stage II patients were symptomatic and 75% had PCR-detectable bacteria. After a mean follow-up of 52.8±32.8 months, all patients with PCR-detectable bacteria in this series were persistently symptomatic requiring treatment. Discussion 36.6% of patients with sarcoidosis had detectable bacterial DNA on presentation, all of these patients were quite symptomatic and most were radiographically advanced stage II. These findings suggest that bacterial DNA-positive, symptomatic patients have more aggressive sarcoidosis that persists long term and might benefit from antimicrobial treatment directed against this presumed chronic granulomatous infection.

correspondence: Marilyn M Bui Department of Anatomic Pathology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, UsA Tel +1 813 745 4940 Fax +1 813 745 5970 Email marilyn.bui@moffitt.org Background: Fibrous dysplasia is an uncommon bone disease that has rare but clear potential for malignant transformation. The frequency is increased in polyostotic forms, McCune–Albright syndrome, Mazabraud’s syndrome, and previously irradiated sites. Rapidly progressing pain unrelated to trauma is the most concerning symptom. The early radiological features of sarcomatous transformation are moth-eaten or cystic areas of osteolysis, cortical destruction, and gradual formation of a soft tissue mass. The prognosis is unfavorable as most of the cases are in an advanced stage at the time of diagnosis. Methods: This case was diagnosed at a large cancer center in Florida. Pertinent clinical findings were obtained from chart review and inter-departmental consultation. Results: Histopathological examination revealed dysplastic lamellar bone with no osteoblastic rimming and “Chinese letter” shapes, areas composed of lobulated hyaline cartilage with mild to severe nuclear atypia, and areas of poorly differentiated cells with a spindled appearance, consistent with chondrosarcoma arising within fibrous dysplasia. Conclusions: Sarcomatous transformation of fibrous dysplasia is an uncommon occurrence, yet has significant importance for those with the disease. There may be difficulty with diagnosis given the symptoms and radiologic findings of benign fibrous dysplasia. We report a case of chondrosarcoma rising in fibrous dysplasia and review the current literature. This case is of interest due to the fact that the diagnosis of monostotic fibrous dysplasia was first made at the age of 59 and malignant transformation occurred within a decade with no history of trauma or radiation. This is an excellent example of how a change in symptoms without a history of trauma should be alarming to the clinician and warrants a thorough work-up for malignancy. To the best of our knowledge, this represents the second case of dedifferentiated chondrosarcoma within the English literature.