Do we really care about incidental lung nodules?-Review of atypical lung carcinoid and a proposal for systematic patient follow up.

Atypical lung carcinoids are intermediate-grade neuroendocrine tumors (NETs) with malignant potential. They are often detected incidentally on imaging done for non-related causes, as the patients are frequently asymptomatic. Histopathology is required to confirm the diagnosis with immunohistochemistry (IHC). Due to their indolent nature, these are often diagnosed only in the advanced stages. Treatment options include chemoradiation for widespread disease versus surgery for local or minimally invasive disease. This article describes a nonsmoker female with enlarging solitary pulmonary nodule who was initially lost to follow up, subsequently operated and with final pathology revealing atypical lung carcinoid. This case stress on the schematic follow up of these incidentally detected pulmonary nodules. Inspired from the mandatory lay mammography report letters recommended by ACR, this article proposes sending lay letters to patients for pulmonary nodule follow up, directly from the Radiology Department to reinforce the importance of timely follow up, which will complement the information provided to the patient from their primary care physician or pulmonologist's office.

Eruptive angiokeratomas and porokeratosis in the setting of sclerodermatous graft-vs.-host disease.

Porokeratosis and angiokeratomas are both seen in the setting of chronic graft-vs.-host disease (GVHD), but rarely occur together. We present a case of a patient with lichen planus-like (LPL) and sclerodermatous chronic GVHD manifesting after allogeneic bone marrow transplant with concomitant eruptive angiokeratomas and porokeratosis.

Renal medullary cancer in a patient with sickle cell trait.

Renal medullary cancer is a rare malignancy almost exclusively seen in young patients of African ethnicity. These patients often present with the cardinal symptoms of hematuria, flank pain, and an abdominal mass, and this malignancy has been associated with patients carrying sickle cell trait. It is estimated that 300 million people worldwide carry sickle cell trait, and the presence of hematuria in these patients should be treated as a harbinger of a possible malignancy. Notably, this tumor mostly develops on the right side of the body. Patients often present with it at an advanced stage and the prognosis is poor. Therefore, a high index of suspicion in a patient of African descent presenting with a right sided abdominal mass and hematuria may assist in an early diagnosis. Current chemotherapy options are very limited, and early detection may provide a chance for surgical resection. It may also provide a bigger time frame for the initiation of novel chemotherapy regimens in patients who fail current chemotherapy regimens.

Uterine sarcoidosis: a rare extrapulmonary site of sarcoidosis.

Sarcoidosis is a multisystem disease which is most commonly manifested in the pulmonary system. However, extrapulmonary manifestations have also been frequently reported. Isolated occurrence of sarcoidosis in the genital system is rare and poses a diagnostic and therapeutic dilemma. Uterine sarcoidosis can present with cervical erosions, endometrial polypoid lesions, and recurrent serometra. In majority of cases, it is diagnosed by endometrial curettage, but it has also been detected by examination of hysterectomy, polypectomy, and autopsy specimens. Nonnecrotizing granulomas are the characteristic pathologic finding of sarcoidosis. However, many infectious and noninfectious etiologies including certain neoplasms can produce similar granulomatous reactions in the female genital tract. These conditions affect the female genital tract more commonly than sarcoidosis, and therefore it is important to rule out these conditions first before making a diagnosis of sarcoidosis. Treatment of sarcoidosis is different from treating these other conditions and the most commonly used systemic or local corticosteroids can be hazardous if the underlying cause is infection. In this case report, the clinical presentation, histopathology, clinical course, and treatment of a patient with isolated uterine sarcoidosis are described, and a brief literature review of sarcoidosis of the female genital tract is provided.

Solitary fibrous tumor of the pleura.

Solitary fibrous tumor of the pleura (SFTP) is a rare tumor of mesenchymal origin which can grow to a large size and present with symptoms of cough and pleuritic chest pain. No specific etiological factors for SFTPs are known and they may grow undetected for several years. These tumors are usually benign and may mimic a variety of malignancies. SFTPs are often detected as peripheral opacities on chest X-ray. Unfortunately, fine needle aspiration rarely provides adequate information for a definitive diagnosis. Imaging with computed tomography provides details about the size and extent of any invasion into adjacent tissues. Surgical resection is the mainstay of treatment, and immunohistochemistry of the resected tumor often provides confirmation of the diagnosis. Some SFTPs have been observed to be malignant, and surgical intervention is often lifesaving. There is no adequate data to support the usage of radiotherapy and chemotherapy in the treatment of SFTPs. This tumor exemplifies malignancies which require surgical resection to preempt worse outcomes. Awareness of their presentation and clinical course may help the clinician provide a prompt referral to the thoracic surgeon for resection.

Estrogen, progesterone, and HER-2 receptor immunostaining in cytology: the effect of varied fixation on human breast cancer cells.

The ASCO/CAP Expert Panel recommends that all invasive breast carcinomas and breast cancer recurrences be tested for ER, PR and HER-2 expression. The guidelines for testing of surgical specimens by immunohistochemistry (IHC) are well defined, whereas they are lacking for cytological samples. We evaluated various fixation protocols for optimal receptor testing by immunohistochemistry and immunocytochemistry (ICC) of human breast cancer cell lines MCF-7 (ER/PR positive) and SKBR-3 (overexpressing HER-2). The cells were fixed in 10% neutral buffered formalin or Saccomanno Fixative (SF) for various time points, and either embedded in paraffin as cell blocks or prepared as cytospins. ER and PR slides were assigned a proportion score (PS; 0-5), an intensity score (IS; 0-3) and a total score (TS = PS + IS). Standard DAKO scoring system ranging from 0 to 3+ was used for the evaluation of HER-2 staining. Human breast cancer cells stained successfully for ER, PR and HER-2 when fixed in formalin and prepared as cell blocks. The optimal fixation time for formalin-fixed cells ranged from 2 to 96 hours. Cells fixed in SF from 2 to 96 hours also stained well for ER and PR. However, SF produced variable results for HER-2 staining; particularly, SF fixation beyond 24 hours caused false negative results. The interpretation of HER-2 staining on cytospins was not feasible irrespective of the fixative and fixation time. In summary, formalin fixation from 2 to 96 hours and preparation of cells as cell blocks produces optimal results for ER, PR, and HER-2 testing in human breast cancer cells.

Use of matrix-assisted laser desorption ionization-time of flight mass spectrometry to resolve complex clinical cases of patients with recurrent bacteremias.

Matrix-assisted laser desorption-ionization time of flight mass spectrometry (MALDI-TOF MS) is a rapid and accurate method of identifying microorganisms. Throughout Europe, it is already in routine use but has not yet been widely implemented in the United States, pending FDA approval. Here, we describe two medically complex patients at a large tertiary-care academic medical center with recurring bacteremias caused by distinct but related species. Bacterial identifications were initially obtained using the Vitek-2 system with the GPI card for Enterococcus and the API system for staphylococci. Initial results misled clinicians as to the source and proper management of these patients. Retrospective investigation with MALDI-TOF MS clarified the diagnosis by identifying a single microorganism as the pathogen in each case. To our knowledge, this is one of the first reports in the United States demonstrating the use of MALDI-TOF MS to facilitate the clinical diagnosis in patients with recurrent bacteremias of unclear source.

Melanoma stem cells in experimental melanoma are killed by radioimmunotherapy.

INTRODUCTION: In spite of recently approved B-RAF inhibitors and immunomodulating antibodies, metastatic melanoma has poor prognosis and novel treatments are needed. Melanoma stem cells (MSC) have been implicated in the resistance of this tumor to chemotherapy. Recently we demonstrated in a Phase I clinical trial in patients with metastatic melanoma that radioimmunotherapy (RIT) with 188-Rhenium((188)Re)-6D2 antibody to melanin was a safe and effective modality. Here we investigated the interaction of MSC with RIT as a possible mechanism for RIT efficacy. METHODS: Mice bearing A2058 melanoma xenografts were treated with either 1.5 mCi (188)Re-6D2 antibody, saline, unlabeled 6D2 antibody or (188)Re-labeled non-specific IgM. RESULTS: On Day 28 post-treatment the tumor size in the RIT group was 4-times less than in controls (P<0.001). The tumors were analyzed by immunohistochemistry and FACS for two MSC markers--chemoresistance mediator ABCB5 and H3K4 demethylase JARID1B. There were no significant differences between RIT and control groups in percentage of ABCB5 or JARID1B-positive cells in the tumor population. Our results demonstrate that unlike chemotherapy, which kills tumor cells but leaves behind MSC leading to recurrence, RIT kills MSC at the same rate as the rest of tumor cells. CONCLUSIONS: These results have two main implications for melanoma treatment and possibly other cancers. First, the susceptibility of ABCB5+ and JARID1B+cells to RIT in melanoma might be indicative of their susceptibility to antibody-targeted radiation in other cancers where they are present as well. Second, specifically targeting cancer stem cells with radiolabeled antibodies to ABCB5 or JARID1B might help to completely eradicate cancer stem cells in various cancers.

Diabetic mastopathy, a clinicopathological correlation of 34 cases.

Diabetic mastopathy (DM) is an unusual fibrous disease of the breast. We report 34 cases with clinicopathological correlation and follow-ups. Patients mean age was 57 years and 24 had histories of diabetes mellitus. The DM presented as a palpable breast mass in 85.3% of the cases clinically. Image findings were often as an irregular hypoechoic mass (44.4%) on ultrasound and negative or non-specific density (67.6%) on mammogram. Histologically, we found that the majority of DM occurred in the upper outer/central part of the breast (76%) and the size ranged from 0.5 to 3.7 cm. All cases showed lymphocytic lobulitis and vasculitis, keloidal fibrosis, lobular atrophy and varying degree of epithelioid fibroblasts. Examining the surrounding normal tissue of the excision specimens revealed that the margins of DM were often poorly circumscribed and irregularly demarcated from the sounding breast tissue. Vascular calcifications were identified in 10 of 24 excisional specimens, suggesting a hypothesis that vascular damage and scar/wounding healing process could contribute to the pathogenesis of DM. Twenty-one cases had repeated procedures for uncertain descriptive diagnosis. This is the largest study of diabetic mastopathy to date with clinical and imagining correlation. Recognition of this benign entity is important to better understanding the pathogenesis and to avoid unnecessary procedures.