Circulating breast-derived DNA allows universal detection and monitoring of localized breast cancer.

BACKGROUND: Tumor-derived circulating cell-free DNA (cfDNA) is present in the plasma of individuals with cancer. Assays aimed at detecting common cancer mutations in cfDNA are being developed for the detection of several cancer types. In breast cancer, however, such assays have failed to detect the disease at a sensitivity relevant for clinical use, in part due to the absence of multiple common mutations that can be co-detected in plasma. Unlike individual mutations that exist only in a subset of tumors, unique DNA methylation patterns are universally present in cells of a common type and therefore may be ideal biomarkers. Here we describe the detection and quantification of breast-derived cfDNA using a breast-specific DNA methylation signature. PATIENTS AND METHODS: We collected plasma from patients with localized breast cancer before and throughout treatment with neoadjuvant chemotherapy and surgery (N = 235 samples). RESULTS: Pretreatment breast cfDNA was detected in patients with localized disease with a sensitivity of 80% at 97% specificity. High breast cfDNA levels were associated with aggressive molecular tumor profiles and metabolic activity of the disease. During neoadjuvant chemotherapy, breast cfDNA levels decreased dramatically. Importantly, the presence of breast cfDNA towards the end of the chemotherapy regimen reflected the existence of residual disease. CONCLUSION: We propose that breast-specific cfDNA is a universal and powerful marker for the detection and monitoring of breast cancer.

Familial Q fever clustering with variable manifestations imitating infectious and autoimmune disease.

Q fever, caused by Coxiella burnetii, can present as an outbreak of acute disease ranging from asymptomatic disease, pneumonia, hepatitis or fever of unknown origin, which can progress to a chronic disease, most frequently endocarditis. The occurrence of Q fever within families is rarely described, and in most cases presents with uniform acute disease manifestations. Here we present a familial cluster of Q fever presenting as highly variable synchronous manifestations in four of five family members, including prolonged fever of unknown origin, asymptomatic carrier state, hepatitis, and chronic endocarditis developing in the absence of previous symptoms. This case series highlights the possibility of Q fever developing in cohabitated individuals with highly variable symptoms masking the common disease etiology. Screening of all exposed individuals, even those not clinically suspected to be infected, may enable to better identify, treat and prevent progression to chronic disease.

Characterization of novel CD55 isoforms expression in normal and neoplastic tissues.

CD55 (decay-accelerating factor, DAF) is overexpressed in several types of cancer, including colorectal cancer. Because of its inhibitory effect on the complement system, it has been suggested as a possible target for cancer immunotherapy. However, CD55 is also expressed in normal tissues, body fluids and stroma, limiting the use of anti-CD55 therapeutic antibodies. Two novel CD55 splice variants or isoforms have recently been identified. These have been shown to contain part or all of intron 7 (CD55(int7+)), in contrast to the previously identified splice variants (CD55(wt)), which do not contain intron 7. Our aim was to determine the pattern of expression of the CD55(int7+) isoforms in normal and cancer tissues and to compare it to CD55(wt). We found that while CD55's isoforms levels vary directly, CD55(wt) is much more abundant (on average 48 times more) than CD55(int7+). Moreover, colon cancers that express high CD55(wt) mRNA levels tend to upregulate CD55(int7+) to a further extent. Finally, we compared the protein levels of CD55(int7+) to CD55(wt) by immunohistochemistry in various colorectal pathological conditions including neoplasia, and found that the levels of both isoforms were elevated in all types of colonic pathology. These results show that the levels of CD55(int7+) in normal tissue are much lower than CD55(wt), while in tumors it is restricted to the epithelial structures unlike CD55(wt). Thus, CD55(int7+) may be a more suitable target for cancer immunotherapy.

Cutaneous changes in fibrous hamartoma of infancy.

BACKGROUND: Fibrous hamartoma of infancy (FHI) is a fast growing soft tissue tumor that usually arises in the first 2 years of life. The histology of the lesion has been well described. Few studies, however, have looked at changes in the overlying skin and its appendages. METHODS: A database search performed at British Columbia Children's Hospital yielded 15 cases of unequivocal FHI occurring in 12 patients (three were recurrences). Of these, we were able to retrieve 13. Five of 13 cases had sections including epidermis. These slides were reviewed with specific emphasis on skin adnexae. RESULTS: Of the cases with excised epidermis in continuity with the lesion, 5/5 had eccrine changes, including hyperplasia, duct dilatation, intraluminal papillary formations, and squamous syringometaplasia. One case showed epidermal basaloid follicular hyperplasia. CONCLUSIONS: This study shows that eccrine changes are frequently seen in cases of FHI when overlying skin is sampled. This may be a useful clue to consider this diagnosis, especially when the biopsy is superficial.

Giant cavernous sinus teratoma: a clinical example of a rare entity: case report.

OBJECTIVE AND IMPORTANCE: Teratomas represent 0.5% of all intracranial tumors. These benign tumors have tissue representative of the three germinal layers: ectoderm, mesoderm, and endoderm. Most teratomas are midline tumors located predominantly in the sellar and pineal regions. Cavernous sinus location is very rare; only two purely intracavernous teratomas have been reported. CLINICAL PRESENTATION: A 14-year-old boy presented with a history of progressive right eye proptosis and visual acuity impairment, headaches, and a neuralgia-like facial pain in the right V1 distribution. A head computed tomographic scan and magnetic resonance imaging disclosed a large tumor filling the right cavernous sinus and extending into the ipsilateral middle fossa. These scans also demonstrated mixed signals derived from different tissues conforming to the tumor (fat, cartilage, muscle strands, bone, and a primordial tooth). Heterogeneous enhancement was seen after infusion of contrast medium. Significant bone erosion and remodeling was evident in the middle fossa floor and right orbit, with secondary proptosis. A presumptive diagnosis of mature teratoma was made. INTERVENTION: With the use of a right frontotemporal interfascial approach, a combined extra- and intradural dissection of the tumor was performed. The lesion entirely occupied the cavernous sinus, laterally displacing the Gasserian ganglion and trigeminal branches (predominantly V1 and V2). The internal carotid artery and Cranial Nerve VI were medially displaced by the tumor mass. The lesion was composed of different tissues, including hair, fat, cartilage, muscle, nerve-like tissue, bone, and a primordial tooth. The tumor was removed completely, and the pathological report confirmed the diagnosis of a mature teratoma. There was no evidence of recurrence at the 8-month follow-up examination. CONCLUSION: Because of the lesion's location in the lateral wall of the cavernous sinus, a total removal was achieved with the use of standard microsurgical techniques. Knowledge of the microanatomy is essential in treating intracavernous pathology. We present the third reported case of a giant mature teratoma of the cavernous sinus.