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.

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.

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.

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.

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.

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.

Vitamin C and alpha-naphthoflavone prevent estrogen-induced mammary tumors and decrease oxidative stress in female ACI rats.

The mechanisms underlying the pathogenesis of estrogen-induced breast carcinogenesis remain unclear. The present study investigated the roles of estrogen metabolism and oxidative stress in estrogen-mediated mammary carcinogenesis in vivo. Female August Copenhagen Irish (ACI) rats were treated with 17beta-estradiol (E(2)), the antioxidant vitamin C, the estrogen metabolic inhibitor alpha-naphthoflavone (ANF), or cotreated with E(2) + vitamin C or E(2) + ANF for up to 8 months. E(2) (3 mg) was administered as an subcutaneous implant, ANF was given via diet (0.2%) and vitamin C (1%) was added to drinking water. At necropsy, breast tumor incidence in the E(2), E(2) + vitamin C and E(2) + ANF groups was 82, 29 and 0%, respectively. Vitamin C and ANF attenuated E(2)-induced alterations in oxidative stress markers in breast tissue, including 8-iso-prostane F(2alpha) formation and changes in the activities of antioxidant enzymes superoxide dismutase and glutathione peroxidase. Quantification of 2-hydroxyestradiol (2-OHE(2)) and 4-hydroxyestradiol (4-OHE(2)) formation in breast tissue confirmed that ANF inhibited 4-hydroxylation of E(2) and decreased formation of the highly carcinogenic 4-OHE(2). These results demonstrate that antioxidant vitamin C reduces the incidence of estrogen-induced mammary tumors, increases tumor latency and decreases oxidative stress in vivo. Further, our data indicate that ANF completely abrogates breast cancer development in ACI rats. The present study is the first to demonstrate the inhibition of breast carcinogenesis by antioxidant vitamin C or the estrogen metabolic inhibitor ANF in an animal model of estrogen-induced mammary carcinogenesis. Taken together, these results suggest that E(2) metabolism and oxidant stress are critically involved in estrogen-induced breast carcinogenesis.

Antioxidant butylated hydroxyanisole inhibits estrogen-induced breast carcinogenesis in female ACI rats.

Exposure to estrogens is suggested to be a risk factor in human breast cancer development. The mechanisms underlying estrogen-induced cancer have not been fully elucidated. Both estrogen receptor (ER)-mediated proliferative processes and ER-independent generation of oxidative stress are suggested to play important roles in estrogen-induced breast carcinogenesis. In the current study, we investigated the role of oxidative stress in breast carcinogenesis using the ACI rat model of mammary tumorigenesis. Female ACI rats were treated with 17beta-estradiol (E(2)), butylated hydroxyanisole (BHA), or a combination of E(2) + BHA for up to 240 days. Cotreatment of rats with E(2) + BHA reduced estrogen-induced breast tumor development with tumor incidence of 24%, a significant decrease relative to E(2) where tumor incidence was 82%. Proliferative changes in the breast tissue of E(2) + BHA-treated animals were similar to those observed in E(2)-treated animals. Tissue levels of 8-isoprostane, a marker of oxidant stress, as well as the activities of antioxidant enzymes including glutathione peroxidase, superoxide dismutase, and catalase were quantified in the breast tissues of rats treated with E(2) + BHA and compared to activity levels found in E(2)-treated animals and respective age-matched controls. Cotreatment with BHA inhibited E(2)-mediated increases in 8-isoprostane levels as well as activities of antioxidant enzymes. In summary, these data suggest that estrogen-mediated oxidant stress plays a critical role in the development of estrogen-dependent breast cancers and BHA inhibits E(2)-dependent breast carcinogenesis by decreasing oxidant stress.

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.

Estrogen-induced breast cancer: alterations in breast morphology and oxidative stress as a function of estrogen exposure.

Epidemiological evidence indicates that prolonged lifetime exposure to estrogen is associated with elevated breast cancer risk in women. Oxidative stress and estrogen receptor-associated proliferative changes are suggested to play important roles in estrogen-induced breast carcinogenesis. In the present study, we investigated changes in breast morphology and oxidative stress following estrogen exposure. Female ACI rats were treated with 17beta-estradiol (E(2), 3 mg, s.c.) for either 7, 15, 120 or 240 days. Animals were euthanized, tissues were excised, and portions of the tissues were either fixed in 10% buffered formalin or snap-frozen in liquid nitrogen. Paraffin-embedded tissues were examined for histopathologic changes. Proliferative changes appeared in the breast after 7 days of E(2) exposure. Atypical ductal proliferation and significant reduction in stromal fat were observed following 120 days of E(2) exposure. Both in situ and invasive carcinomas were observed in the majority of the mammary glands from rats treated with E(2) for 240 days. Palpable breast tumors were observed in 82% of E(2)-treated rats after 228 days, with the first palpable tumor appearing after 128 days. No morphological changes were observed in the livers, kidneys, lungs or brains of rats treated with E(2) for 240 days compared to controls. Furthermore, 8-isoprostane (8-isoPGF(2alpha)) levels as well as the activities of antioxidant enzymes, such as glutathione peroxidase, superoxide dismutase and catalase, were quantified in the breast tissues of rats treated with E(2) for 7, 15, 120 and 240 days and compared to activity levels in age-matched controls. 8-isoPGF(2alpha) levels displayed time-dependent increases upon E(2) treatment and were significantly higher than control levels at the 15, 120 and 240 day time-points. 8-isoPGF(2alpha) observed in E(2)-induced mammary tumors were significantly higher than levels found in control mammary tissue from age-matched animals. Similarly, alterations in glutathione peroxidase and superoxide dismutase activities were detected in both mammary and tumor tissue from E(2)-treated rats. Taken together, our data reveal that proliferative changes in the breast tissue of ACI rats are associated with increases in 8-isoPGF(2alpha) formation as well as changes in the activities of antioxidant enzymes. These oxidative changes appear to be a function of E(2) exposure and occur prior to tumor development.

Clear cell and eosinophilic oncocytomas of salivary gland: cytological variants or parallels?

Oncocytomas are uncommon tumors of the salivary gland. They have an abundance of mitochondria, which is manifested as granular eosinophilic cytoplasm by light microscopy. On histological sections, presence of cytoplasmic glycogen and/or fixation artifact can impart cytoplasmic clearing, and oncocytomas with a predominance of clear cytoplasm are labeled clear cell oncocytomas. Two forms of oncocytoma, eosinophilic and clear cell, have been described in the surgical pathology literature. The purpose of this manuscript is to conduct a comparative cytological assessment to ascertain parallels and differences between the two variants.

Usefulness of CDX2 and TTF-1 in differentiating gastrointestinal from pulmonary carcinoids.

Carcinoids of different organs appear morphologically indistinguishable. We studied the usefulness of differential expression of CDX2 and thyroid transcription factor-1 (TTF-1) in 78 gastrointestinal and pulmonary carcinoids and their metastases (n = 10). CDX2 staining of gastric biopsy specimens with neuroendocrine hyperplasia (n = 11) and various gastritides (n = 10) was also performed. All ileal (6/6 [100%]), 6 (86%) of 7 appendiceal, 3 (75%) of 4 duodenal, 1 (50%) of 2 ampullary, 12 (33%) of 18 rectal, 6 (30%) of 20 pancreatic, and 1 (17%) of 6 gastric carcinoids expressed CDX2 with variable intensity; none of the pulmonary carcinoids stained. Of 15 pulmonary carcinoids, 8 (53%) stained with TTF-1, but none of the gastrointestinal carcinoids did. CDX2 and TTF-1 staining profiles of primary and metastatic carcinoids were similar. CDX2+ gastric endocrine cells had a distribution similar to that of gastrin and enterochromaffin cells but not enterochromaffin-like cells. Our results suggest that CDX2 and TTF-1 have high specificity for gastrointestinal and pulmonary carcinoids, respectively.

Ectopic hamartomatous thymoma: a clinicopathologic and immunohistochemical analysis of 21 cases with data supporting reclassification as a branchial anlage mixed tumor.

This report describes the clinicopathologic and immunohistochemical findings in 21 cases of a highly distinctive tumor with a strong predilection for the lower neck region of adult males. Our study group consisted of 20 males and one female. The patients were 28 to 79 years old (mean age, 47 years; median age, 40 years), and they presented with solitary, lobular or multilobular masses ranging in size from 2.0 to 19.0 cm in greatest dimension (mean size, 5.1 cm; median, 4 cm). The tumors principally involved the lower neck region, usually in close proximity to the sternoclavicular joint. The preoperative duration of the lesions ranged from 2 months to 30 years. Histologically, the tumors were typically well marginated and composed of plump spindled cells, delicate spindled cells, mature adipose tissue, and epithelial cells, including both squamous and glandular elements. Epithelial-lined cysts were a focal finding in most cases and measured up to 2 cm in greatest dimension. Mitotic counts for the tumors ranged from 0 to 7 mitotic figures per 50 high power fields (mean mitotic count, 1.1 mitotic figures per 50 HPFs). Our immunohistochemical analysis revealed a complex immunophenotype with a diverse keratin profile. The plump spindled cells had a myoepithelial phenotype, as evidenced by the coexpression of keratins (5, 5/6, and 14), alpha-smooth muscle actin, CD10, and to a lesser extent, calponin. No compelling evidence for thymic differentiation was observed. The patients were initially managed by biopsy or partial resection (n = 4), simple local excision (n = 16), or an unspecified procedure (n = 1). Clinical follow-up of > or =3 years was available for 10 patients (48%). Two patients had recurrent disease, but there were no metastases or tumor-related deaths. A derivation from sequestered branchial epithelium is likely, but evidence for a thymic component is tenuous, at best. Our data support reclassification of this distinctive process as a branchial anlage mixed tumor. The differential diagnosis includes conventional mixed tumors of skin adnexal or salivary gland origin, synovial sarcoma, a peripheral nerve sheath tumor variant, and cystic teratoma.

Tenosynovial (extraarticular) chondromatosis: an analysis of 37 cases of an underrecognized clinicopathologic entity with a strong predilection for the hands and feet and a high local recurrence rate.

Tenosynovial chondromatosis is a multinodular cartilaginous proliferation that arises from the tenosynovial membranes. This report describes the clinical, radiologic, and histopathologic findings in 37 cases of this uncommon entity. There were 17 males and 20 females, ranging in age from 20 to 86 years (mean and median age, 46 years). The process involved tenosynovium of the fingers (n = 19), feet (n = 8), wrists (n = 4), ankles (n = 2), hand, not otherwise specified, or palm (n = 2), knee (n = 1), and forearm (n = 1). Signs of disease or symptoms were present for 5 weeks to 18 years (median duration, approximately 2 years) before surgical excision. The two most common complaints were a painless mass and a mass that was mildly tender with pressure. None of the tumors had clinical, radiologic, or histopathologic evidence of articular or bone involvement. Histologically, all tumors consisted of a multinodular cartilaginous proliferation involving tenosynovium and/or subsynovial connective tissue. Mild or moderate atypia, as encountered in chondroma of soft parts and synovial chondromatosis, was a frequent finding. Follow-up information was available for 16 patients (43%). Only two patients with follow-up information remained disease free after their initial surgical procedure. Seven patients had one recurrence and seven patients had two or more recurrences. Tenosynovial chondromatosis appears to be an extraarticular counterpart of synovial (intraarticular) chondromatosis. Our review indicates this process is often confused with chondroma of soft parts, in part, because both entities have a predilection for the hands and feet. Diagnosis of this underrecognized entity is of clinical importance because of the high local recurrence rate.