Fibrous hamartoma of infancy: imaging findings.

BACKGROUND: Fibrous hamartoma of infancy is a benign tumor that typically arises within the first 2 years of life in the subcutaneous and lower dermal layers. Diagnosis can be challenging as it is a rare tumor, and the imaging appearance is not well known. OBJECTIVE: To describe the imaging features in 4 cases of fibrous hamartoma of infancy focusing on ultrasound (US) and magnetic resonance (MR) findings. MATERIALS AND METHODS: In this retrospective IRB-approved study, informed consent was waived. We searched patient charts for histopathology-confirmed fibrous hamartoma of infancy diagnosis between November 2013 and November 2022. We found four cases, three boys and one girl, and the mean age was 1.4 years (5 months-3 years). The lesions were located in the axilla, posterior elbow, posterior neck, and lower back. All four patients underwent ultrasound evaluation of the lesion, and two patients also underwent MRI evaluation. The imaging findings were reviewed by consensus by two pediatric radiologists. RESULTS: US imaging revealed subcutaneous lesions with variably defined hyperechoic regions and intervening hypoechoic bands resulting in a linear "serpentine" pattern or a "multiple semicircle" pattern. MR imaging evidenced heterogeneous soft tissue masses, localized in the subcutaneous fat, and showed hyperintense fat interspersed with hypointense septations on both T1- and T2-weighted images. CONCLUSION: Fibrous hamartoma of infancy has a suggestive appearance on US with heterogeneous, echogenic subcutaneous lesions with intervening hypoechoic portions, in parallel or circumferential arrangement that can be seen as a serpentine or semicircular pattern. On MRI, interspersed macroscopic fatty components show high signal intensity on T1- and T2-weighted images and reduced signal on fat-suppressed inversion recovery images, with irregular peripheral enhancement.

Surgical management of dermatofibrosarcoma protuberans.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon, locally aggressive cutaneous malignancy. Complete resection is the primary treatment but there is debate over the optimal method. Wide local excision was traditionally the standard of care; however, National Comprehensive Cancer Network guidelines now recommend Mohs micrographic surgery as the preferred approach. Medical therapy with imatinib can be used in advanced or unresectable disease. This review will discuss the current management of DFSP, focusing on optimal surgical approach.

Papillary Intralymphatic Angioendothelioma in a Child With PIK3CA-Related Overgrowth Spectrum: Implication of PI3K Pathway in the Vascular Tumorigenesis.

Papillary intralymphatic angioendothelioma (PILA) is an extremely rare vascular tumor and its pathogenesis is unknown. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-related overgrowth spectrum (PROS) is a heterogeneous group of disorders caused by mosaicism for activating mutations of PIK3CA and characterized by asymmetric overgrowth, skeletal anomalies, skin lesions, and vascular malformations. An association between PILA and PROS has not been known. We report a case of PILA involving the spleen of a young girl with the clinical and molecular diagnosis of PROS. Sequencing of the patient's germ-line DNA detected a pathogenic PIK3CA variant c.1357G>A in 10.6% of alleles. Splenectomy revealed a 4-cm tumor composed of ectatic lymphatics with intraluminal papillary projections, consistent with PILA. The tumor cells showed immunohistochemical expression of CD31, CD34, ERG, FLI-1, PROX1, and caldesmon, while D2-40 was negative. The latter may suggest that the tumor derived from an endothelial precursor arrested in the final steps of lymphothelial differentiation, in keeping with the known role of the PIK3CA-governed molecular pathway in the progression of vascular progenitors to mature endothelial cells. The data implicates PIK3CA in the pathogenesis of PILA and broadens the spectrum of phenotypic expressions of PROS.

Analysis of lumbar spine stenosis specimens for identification of amyloid.

BACKGROUND: Lumbar spinal stenosis (LSS) is a common reason for spine surgery in which ligamentum flavum is resected. Transthyretin (TTR) amyloid is an often unrecognized and potentially modifiable mechanism for LSS that can also cause TTR cardiac amyloidosis. Accordingly, older adult patients undergoing lumbar spine (LS) surgery were evaluated for amyloid and if present, the precursor protein, as well as comprehensive characterization of the clinical phenotype. METHODS: A prospective, cohort study in 2 academic medical centers enrolled 47 subjects (age 69 ± 7 years, 53% male) undergoing clinically indicated LS decompression. The presence of amyloid was evaluated by Congo Red staining and in those with amyloid, precursor protein was determined by laser capture microdissection coupled to mass spectrometry (LCM-MS). The phenotype was assessed by disease-specific questionnaires (Swiss Spinal Stenosis Questionnaire and Kansas City Cardiomyopathy Questionnaire) and the 36-question short-form health survey, as well as biochemical measures (TTR, retinol-binding protein, and TTR stability). Cardiac testing included technetium-99m-pyrophosphate scintigraphy, electrocardiograms, echocardiograms, and cardiac biomarkers as well as measures of functional capacity. RESULTS: Amyloid was detected in 16 samples (34% of participants) and was more common in those aged ≥ 75 years of age (66.7%) compared with those <75 years (22.3%, p < 0.05). LCM-MS demonstrated TTR as the precursor protein in 62.5% of participants with amyloid while 37.5% had an indeterminant type of amyloid. Demographic, clinical, quality-of-life measures, electrocardiographic, echocardiographic, and biochemical measures did not differ between those with and without amyloid. Among those with TTR amyloid (n = 10), one subject had cardiac involvement by scintigraphy. CONCLUSIONS: Amyloid is detected in more than a third of older adults undergoing LSS. Amyloid is more common with advancing age and is particularly common in those >75 years old. No demographic, clinical, biochemical, or cardiac parameter distinguished those with and without amyloid. In more than half of subjects with LS amyloid, the precursor protein was TTR indicating the importance of pathological assessment.

A Case of Pediatric Stroke: Osteosarcoma Embolus in the Internal Carotid Artery.

Stroke in the pediatric population is rare. Despite presentation similar to that seen in the adult patient, the diagnosis in a child can be missed or mistaken for a more common stroke mimic. Due to its rarity, there are no completed pediatric clinical trials investigating best treatment, though guidelines have been extrapolated from adult guidelines and retrospective cohort studies to include some combination of thrombolysis and mechanical thrombectomy. Rarer still is pediatric stroke caused by tumor embolus. We present the case of a young child diagnosed with stroke secondary to osteosarcoma embolism to the left internal carotid artery and review the relevant literature to discuss the considerations and challenges of treatment of stroke in the pediatric population.

Tumor-induced osteomalacia - Current imaging modalities and a systematic approach for tumor localization.

Paraneoplastic syndromes are symptom complexes that cannot be readily explained by local or distant spread of the tumor. They can occur due to hormone production, autoimmunity or other biologically active products produced by the tumor, etc. Tumor induced osteomalacia is a rare paraneoplastic syndrome in which the manifestation is mainly musculoskeletal such as bone pain, fractures and muscle weakness as a consequence of elaboration of fibroblast growth factor 23 (FGF23) by the tumor. Most of these tumors are solitary and small and hence localization of these tumors is often challenging. This review summarizes the various anatomic imaging modalities such as plain radiographs, computed tomography (CT), and magnetic resonance imaging (MRI) and nuclear medicine imaging techniques in the evaluation of these tumors.

Cytological diagnosis of angiosarcoma arising in an immunosuppressed patient 6 years after multi-visceral transplantation: a case report and literature review.

Angiosarcoma is a rare and aggressive malignant tumor of soft tissue. It can arise in almost any part of the body, most commonly in the skin and the superficial soft tissue in the head and neck region. Although the etiology of angiosarcoma is unknown, there are several well-known risk factors, such as chronic lymphedema, exposure to radiation, toxins, and foreign bodies. It rarely occurs in transplant patients. Cytological criteria for the diagnosis of angiosarcoma have not been fully established, having been described only in a few cases, mostly fine-needle aspiration biopsies (FNAB). Herein, we present a case of angiosarcoma arising in an immunosuppressed patient status post multi-visceral transplantation and diagnosed by cytology. To the best of our knowledge, this is the first report of such a case in the English literature. The cytological findings from endoscopic ultrasound-guided FNAB and ascites fluid are discussed.

Nonneoplastic lesions that simulate primary tumors of bone.

CONTEXT: The skeletal system may be affected by a variety of nonneoplastic lesions, which may potentially be confused with primary bone tumors on clinical, radiologic, and pathologic grounds. These conditions include fractures, infections, and reactive and degenerative processes, as well as an array of quasineoplastic entities, such as intramedullary cystic lesions like unicameral and aneurysmal bone cysts; fibro-osseous lesions, such as fibrous dysplasia; and exophytic entities, like osteochondromas. OBJECTIVE: To review clinical, radiographic, and histologic features of nonneoplastic lesions of bone, discussing the difficulties in diagnosis and the differential diagnosis with primary neoplasms of bone. DATA SOURCES: The sources include the more relevant medical literature on the different subjects and case-derived material. CONCLUSIONS: Because many nonneoplastic bone lesions may require biopsy or resection, the general surgical pathologist must be familiar with these lesions and be aware that review of hematoxylin-eosin slides is only one of the many steps in the diagnostic process, which also includes review of imaging studies and all available clinical information. Morphologic analysis disconnected from the clinical and radiographic context may lead to misinterpretation.

PPARγ agonists enhance ET-743-induced adipogenic differentiation in a transgenic mouse model of myxoid round cell liposarcoma.

Myxoid round cell liposarcoma (MRCLS) is a common liposarcoma subtype characterized by a translocation that results in the fusion protein TLS:CHOP as well as by mixed adipocytic histopathology. Both the etiology of MRCLS and the mechanism of action of TLS:CHOP remain poorly understood. It was previously shown that ET-743, an antitumor compound with an unclear mechanism of action, is highly effective in patients with MRCLS. To identify the cellular origin of MRCLS, we engineered a mouse model in which TLS:CHOP was expressed under the control of a mesodermally restricted promoter (Prx1) in a p53-depleted background. This model resembled MRCLS histologically as well as functionally in terms of its specific adipocytic differentiation-based response to ET-743. Specifically, endogenous mesenchymal stem cells (MSCs) expressing TLS:CHOP developed into MRCLS in vivo. Gene expression and microRNA analysis of these MSCs showed that they were committed to adipocytic differentiation, but unable to terminally differentiate. We also explored the method of action of ET-743. ET-743 downregulated TLS:CHOP expression, which correlated with CEBPα expression and adipocytic differentiation. Furthermore, PPARγ agonists enhanced the differentiation process initiated by ET-743. Our work highlights how clinical observations can lead to the generation of a mouse model that recapitulates human disease and may be used to develop rational treatment combinations, such as ET-743 plus PPARγ agonists, for the treatment of MRCLS.

Is the etiology of pretibial cyst formation after absorbable interference screw use related to a foreign body reaction?

BACKGROUND: Arthroscopically assisted anterior cruciate ligament reconstruction using a bioabsorbable tibial fixation screw is occasionally complicated by pretibial cyst formation. The few case reports describing pretibial cyst formation noted several graft types and fixation techniques, making it difficult to establish one etiology. Some literature suggests cysts form from communication between the joint and pretibial area leading to extravasation of joint fluid, maturing into a cyst. We propose the development of cysts after PLLA screw use may be related to a foreign body reaction. QUESTIONS/PURPOSES: We propose this foreign body reaction (1) relates to the biochemical breakdown of bioabsorbable materials; and (2) differs from cystic formations resulting from joint communication. METHODS: We retrospectively reviewed seven patients who developed pretibial cysts at least 2 years after original primary ACL reconstruction surgery. MRI was used to visualize the extent of cystic formation. Cysts were treated by débridement with specimens sent for histologic analysis. Cyst appearance had a 3-year incidence of 5%. RESULTS: No cyst had an infectious etiology. In all cases, the tibial screw outline was present on MRI, although intraoperatively, the screw was substantially decomposed. Grafts were well incorporated and none of the knees demonstrated anterior laxity. Histologically, cyst material contained fragments of PLLA surrounded by foamy histiocytes, suggesting a foreign body reaction. No cysts recurred. CONCLUSIONS: Tibial cysts occur in a subset of patients undergoing ACL reconstruction using a bioabsorbable PLLA interference screw. We suspect they arise from a foreign body response to the screw breakdown. Removal is well tolerated. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Dietary quercetin exacerbates the development of estrogen-induced breast tumors in female ACI rats.

Phytoestrogens are plant compounds that structurally mimic the endogenous estrogen 17beta-estradiol (E(2)). Despite intense investigation, the net effect of phytoestrogen exposure on the breast remains unclear. The objective of the current study was to examine the effects of quercetin on E(2)-induced breast cancer in vivo. Female ACI rats were given quercetin (2.5 g/kg food) for 8 months. Animals were monitored weekly for palpable tumors, and at the end of the experiment, rats were euthanized, breast tumor and different tissues excised so that they could be examined for histopathologic changes, estrogen metabolic activity and oxidant stress. Quercetin alone did not induce mammary tumors in female ACI rats. However, in rats implanted with E(2) pellets, co-exposure to quercetin did not protect rats from E(2)-induced breast tumor development with 100% of the animals developing breast tumors within 8 months of treatment. No changes in serum quercetin levels were observed in quercetin and quercetin+E(2)-treated groups at the end of the experiment. Tumor latency was significantly decreased among rats from the quercetin+E(2) group relative to those in the E(2) group. Catechol-O-methyltransferase (COMT) activity was significantly downregulated in quercetin-exposed mammary tissue. Analysis of 8-isoprostane F(2alpha) (8-iso-PGF(2alpha)) levels as a marker of oxidant stress showed that quercetin did not decrease E(2)-induced oxidant stress. These results indicate that quercetin (2.5 g/kg food) does not confer protection against breast cancer, does not inhibit E(2)-induced oxidant stress and may exacerbate breast carcinogenesis in E(2)-treated ACI rats. Inhibition of COMT activity by quercetin may expose breast cells chronically to E(2) and catechol estrogens. This would permit longer exposure times to the carcinogenic metabolites of E(2) and chronic exposure to oxidant stress as a result of metabolic redox cycling to estrogen metabolites, and thus quercetin may exacerbate E(2)-induced breast tumors in female ACI rats.

Fine-needle aspiration cytology of subcutaneous toxoplasmosis: A case report.

Toxoplasmosis is a common opportunistic infection in patients with AIDS in whom it typically presents as encephalitis, pneumonia, lymphadenitis, and myocarditis. Skin involvement is very rare and, to our best knowledge, Toxoplasma gondii forming a subcutaneous mass has not been reported. Here, we report the findings of an interesting case of subcutaneous toxoplasmosis with the cytological appearance of an inflammatory fibrovascular lesion in a HIV-positive patient and discuss the differential diagnosis.

Characterization and comparison of the properties of sarcoma cell lines in vitro and in vivo.

To expand the available tools for investigating human sarcomas, we characterized the primary properties of 22 common, uncommon, and newly characterized sarcoma cell lines representing eight different histological subtypes. Throughout the characterization process we noticed that in vitro markers and assays are poor indicators of tumorigenicity and that generated xenografts often bear little resemblance to the original histopathology. In vitro properties examined included morphology, proliferation rate, cell cycle characteristics, invasiveness, and immunohistochemical expression of p53 and phospho-AKT. In vivo properties examined included days to tumor formation in NOD/SCID mice, xenograft morphology in several locations and immunohistochemical expression of Ki67, p53 and phospho-AKT. We believe that such an in depth comparison of a large cohort of sarcoma cell lines will be useful in both designing and interpreting experiments aimed at elucidating both the molecular biology and efficacy of therapeutic agents in sarcomas. However, that data generated also suggests a small set of sarcoma cell lines may be inappropriate for generalizations regarding biological behavior of specific sarcoma subtypes. Integration of functional genomics or other more sophisticated assays of cell lines may help bridge the differences in vitro and in vivo.