Novel FEMASK-score, a histopathologic assessment for destructive Charcot neuropathic arthropathy, reveals intraneural vasculopathy and correlates with progression and best treatment.

BACKGROUND: Charcot neuropathic arthropathy is a debilitating, rapidly destructive degenerative joint disease that occurs in diabetic, neuropathic midfoot. Clinicoradiologic assessment for Charcot neuropathic arthropathy previously relied on Eichenholtz stage. There is limited histopathologic data on this entity. We wanted to independently develop a histopathologic scoring system for Charcot neuropathic arthropathy. DESIGN: Retrieval of surgical pathology midfoot specimens from Charcot patients (2012-2019) were analyzed to evaluate joint soft tissue and bone. Considering progression from large (≥half 40× hpf) to small (

Linguine sign in musculoskeletal imaging: calf silicone implant rupture.

Imaging findings of breast silicone implant rupture are well described in the literature. On MRI, the linguine sign indicates intracapsular rupture, while the presence of silicone particles outside the fibrous capsule indicates extracapsular rupture. The linguine sign is described as the thin, wavy hypodense wall of the implant within the hyperintense silicone on T2-weighted images indicative of rupture of the implant within the naturally formed fibrous capsule. Hyperintense T2 signal outside of the fibrous capsule is indicative of an extracapsular rupture with silicone granuloma formation. We present a rare case of a patient with a silicone calf implant rupture and discuss the MRI findings associated with this condition.

Risk factors for recurrence and prognosis of low-grade endometrial adenocarcinoma; vaginal versus other sites.

Endometrial adenocarcinoma is the most common gynecologic cancer in the United States. The prognosis is generally favorable, however, a significant number of patients do develop local or distant recurrence. The most common site of recurrence is vaginal. Our aim was to better characterize patients with vaginal recurrence of low-grade endometrioid adenocarcinoma with respect to associated tumor parameters and clinical outcome. We compiled 255 cases of low-grade (FIGO Grade I or II) endometrioid adenocarcinoma on hysterectomy specimens with lymph node dissection. A total of 113 cases with positive lymph nodes or recurrent disease were included in our study group. Seventy-three cases (13 Grade 1, 60 Grade 2) developed extravaginal recurrence and 40 cases (7 Grade 1, 33 Grade 2) developed vaginal recurrence. We evaluated numerous tumor parameters including: percentage myoinvasion, presence of microcystic, elongated, and fragmented pattern of myoinvasion, lymphovascular space invasion, and cervical involvement. Clinical follow-up showed that 30% (34/113) of all patients with recurrent disease died as a result of their disease during our follow-up period, including 31 (42.5%) with extravaginal recurrence and 3 (7.5%) with primary vaginal recurrence (P=0.001). The 3 patients with vaginal recurrence developed subsequent extravaginal recurrence before death. Vaginal recurrence patients show increased cervical involvement by tumor, but lack other risk factors associated with recurrent disease at other sites. There were no deaths among patients with isolated vaginal recurrence, suggesting that vaginal recurrence is not a marker of aggressive tumor biology.

Knee popping and clicking in a pediatric athlete: meniscal injury or sports tumor?

This case report presents a teenage patient who initially was thought to have a sports-related injury but ultimately was diagnosed with a primary soft tissue tumor. A previously healthy 16-year-old softball player presented with a history of left knee joint line pain, clicking, and swelling. The patient was presumed to have a lateral meniscus tear. However, magnetic resonance imaging demonstrated an intra-articular mass. Arthroscopy revealed a 2.5- × 1.5-cm firm pedicular mass in the lateral joint. Histological exam demonstrated localized pigmented villonodular synovitis. The patient healed uneventfully and returned to sporting activities. This report re-emphasizes the possibility that "sports tumors" can mimic symptoms of a meniscal tear in young athletes.

Attenuation of arthritis in rodents by a novel orally-available inhibitor of sphingosine kinase.

UNLABELLED: Pro-inflammatory cytokines like TNF-α activate sphingosine kinase (SK). Therefore, inhibition of SK is a potential molecular target for the treatment of rheumatoid arthritis. AIMS: The primary goal of this study was to assess the efficacy of ABC249640 (a selective SK-2 inhibitor) in two models of rodent arthritis. A secondary goal was to evaluate the pharmacological profile of ABC294640, when given in combination with methotrexate. METHODS: The efficacy of ABC294640 was determined by paw diameter/volume measurements, histological evaluations, and micro-CT analyses. RESULTS: ABC294640 attenuated both collagen-induced arthritis in mice, as well as adjuvant-induced arthritis in rats. With the adjuvant arthritis model, the prophylactic efficacy profile of ABC294640 was similar to indomethacin. Of note, ABC294640 reduced the bone and cartilage degradation, associated with adjuvant-induced arthritis. Rats treated with a suboptimal dose of MTX (50 µg/kg/day) in combination with ABC249640 (100 mg/kg/day) had better anti-arthritis effects in the adjuvant model, than treatment with either agent alone. CONCLUSION: Our results suggest that ABC249640 is an orally available drug candidate with a good pre-clinical efficacy profile for the prevention and/or treatment of RA.

Matched unrelated umbilical cord blood transplantation for a patient with chemotherapy resistant Wilms tumor.

We report a patient with chemotherapy refractory Wilms tumor who underwent an unrelated donor cord blood transplant for chemotherapy refractory disease. The preparative regimen consisted of busulfan, melphalan, and anti-thymocyte globulin, and was well tolerated. This patient did not experience significant toxicity related to the chemotherapy regimen and did not develop any graft versus host disease from his HLA (A, B, DR) 6/6 matched cord blood transplant. Follow-up CT scans 2 years post-transplant have shown no evidence of disease progression, with only a few pulmonary nodules remaining, which are unchanged in size from his pre-transplant CT scan. It is possible that high-dose chemotherapy and stem cell transplantation can be curative in patients with tumors that are non-responsive to conventional chemotherapy.

CD10-positive myxofibrosarcomas: a pitfall in the differential diagnosis of atypical fibroxanthoma.

CD10 is now commonly used to differentiate atypical fibroxanthoma (AFX) from melanoma, spindle cell and dedifferentiated variants of squamous cell carcinoma and leiomyosarcoma. However, we have encountered CD10-positive tumors that mimicked AFX but proved to be myxofibrosarcomas. The purpose of this study was to evaluate CD10 expression in a wide range of mesenchymal neoplasms that may involve the skin using tissue microarrays. Our results indicate that in addition to AFX, CD10 expression is common in myxofibrosarcomas, undifferentiated pleomorphic sarcomas, dermatofibromas and dermatofibrosarcoma protuberans. Myxofibrosarcomas commonly present in the skin and may be difficult to distinguish from AFX on small biopsies and CD10 positivity may confound the diagnostic difficulty.

A case report of brown tumor in a patient with chronic renal failure and renal cell carcinoma.

We report a case of a 72 year old male with hyperparathyroidism secondary to end stage diabetic renal disease and coexisting bilateral chromophobe renal cell carcinomas. The patient presented with back and groin pain, right pelvic hemorrhage, and multiple lytic bone lesions concerning for metastatic renal cell carcinoma. Fine needle aspiration cytology demonstrated benign appearing osteoclasts and spindled cells. A concurrent core biopsy showed foci of spindled cell proliferation populated by osteoclast-like giant cells with stromal hemorrhage without evidence of metastatic carcinoma. The cytologic and histologic findings, in correlation with the clinical history, radiographic features, markedly increased parathyroid hormone levels and other serologic studies, were diagnostic of the reactive lesion seen in brown tumor of hyperparathyroidism secondary to chronic renal failure.

A case of vasculopathy of unknown etiology associated with fatal hydrops fetalis and review of the literature on intimomedial mucoid degeneration.

Non-immune hydrops fetalis (NIHF) has a high mortality rate [1]. Many etiologies of NIHF have been identified, including cardiovascular abnormalities, severe anemia, and genetic defects. In patients with cardiovascular etiology, structural malformations lead to fluid accumulation resulting in increased intravascular hydrostatic pressure. We report a fatal case of NIHF in a 31 week gestational age, Caucasian neonate with heart remodeling associated with a stenotic vasculopathy of the right pulmonary artery. The artery revealed partial occlusion with vascular wall abnormalities, including disarrayed smooth muscle fibers, hyperplasia within the tunica media, and myxoid change within the media and intima. Identical vasculopathy was also identified within a mesenteric artery, and this contributed to hemorrhage and early ischemic necrosis of the small intestine, discovered on postmortem examination.

Class I alcohol dehydrogenase is highly expressed in normal human mammary epithelium but not in invasive breast cancer: implications for breast carcinogenesis.

Detoxification of ethanol can contribute to oxidative cellular and DNA damage and, thereby, to carcinogenesis. The potential relevance of this to breast carcinogenesis is suggested by evidence that alcohol consumption is a risk factor for breast cancer. It is, however, not known whether ethanol can be metabolized in breast parenchyma. The goal of this study was to determine whether class I and/or IV alcohol dehydrogenase (ADH), medium chain ADHs that can catalyze oxidation of ethanol, are expressed in human breast parenchyma. Normal and neoplastic human breast tissue specimens were examined for class I and IV ADH mRNA by reverse transcription-PCR, for protein by immunocytochemistry and Western analysis, and for their potential to catalyze NAD(+)-dependent oxidation of ethanol. Together, the findings provide evidence that: (a) class I ADH is the medium-chain ADH that is expressed in human breast parenchyma, specifically in the mammary epithelium; (b) human breast parenchyma can support ADH-mediated oxidation of ethanol; and (c) the expression of class I ADH is dramatically reduced or abrogated in invasive breast cancers. Expression of class I ADH in normal human breast parenchyma was confirmed by probing a multiple human tissue polyA(+)RNA. The unexpected finding of virtual abrogation of expression of class I ADH in invasive breast cancer suggests that the enzyme has some "tumor suppressor" function in the mammary epithelium. The one property of class I ADH fitting this designation is its potential to catalyze the oxidation of the micronutrient/prohormone retinol to retinal, the first step in the biosynthesis of retinoic acid, the principal known mediator of the actions of retinoids important for maintaining epithelia in a differentiated state.

Hybrid Neurofibroma-Schwannoma.

Neurofibromas and schwannomas are common lesions that may be idiopathic or may occur in association with neural crest genetic syndromes such as neurofibromatosis type 1, neurofibromatosis type 2, and schwannomatosis. A hybrid tumor that contains pathological characteristics of both neurofibroma and schwannoma has been described as a rare entity. We present the clinical, radiographic, and pathological findings of such a case.

Intraventricular Undifferentiated Pleomorphic Sarcoma: A Case Report.

Undifferentiated pleomorphic sarcoma is a histologic diagnosis based on cell morphology. These tumors are found throughout the body. They are rarely found in the central nervous system and almost never occur as a primary intraventricular tumor. We present the unusual case of a 68-year-old woman with an intraventricular undifferentiated pleomorphic sarcoma. We go on to discuss the clinical presentation, radiographic characteristics, and management paradigm for these rare lesions. Our patient presented with acute confusion, inability to balance a checkbook, and gait imbalance. CT and MRI demonstrated a 4 x 3.6 x 3.6 cm enhancing lesion in the left lateral ventricle abutting the foramen of Monro. Pathology revealed an undifferentiated pleomorphic sarcoma.

Thyroid lymphoma: a single institution's experience.

BACKGROUND: Primary lymphoma of the thyroid gland is uncommon. METHODS: The tumor registry at the Penn State Milton S. Hershey Medical Center was searched for all patients carrying a diagnosis of thyroid lymphoma. All available records for these patients were examined and information regarding patient and tumor characteristics, clinical presentation, interventions, and survival were tabulated. RESULTS: The average age of patient in our series was 67.5 years. There was a 2.7:1 female to male preponderance. Thirteen (60%) patients presented with thyroid nodule(s). Eleven (50%) presented with aerodigestive tract obstructive symptoms. Sixteen (73%) patients had no pre-existing history of thyroid disease; none had known pre-existing Hashimoto's thyroiditis. CONCLUSIONS: The typical thyroid lymphoma patient is female and elderly with painless thyroid enlargement. Compressive symptoms of the aerodigestive tract are common at presentation and may require urgent intervention. Treatment modalities (XRT, CHOP chemotherapy) and outcomes are distinct from other thyroid malignancies.

Risk factor analysis of recurrence in low-grade endometrial adenocarcinoma.

Prognosis of endometrial adenocarcinoma is favorable; however, the risk of recurrence ranges from 7% to 13%. Recurrence has been related to age, tumor type, International Federation of Gynecology and Obstetrics grade, depth of invasion, and lymphovascular invasion (LVI); however, morphologic features that would predict the site of recurrence have not been established. In this multi-institutional study, we reviewed 589 patients with International Federation of Gynecology and Obstetrics grades 1 or 2 endometrial adenocarcinoma, endometrioid type. Cox proportional hazard analysis was used to identify univariate and multivariate risk factors for recurrence and survival. Univariate analysis revealed features of tumors that recurred only in the vagina: low nuclear grade; superficial myoinvasion; minimal to no LVI; and minimal myoinvasion with microcystic, elongated, and fragmented (MELF) pattern; low nuclear grade and superficial myoinvasion persisted on multivariate analysis. Features of tumors that recurred at other sites included large size, deep myoinvasion, tumor necrosis, 1 or more LVI foci, LVI foci distant/deeper than invasive tumor front, MELF myoinvasion pattern, lower uterine segment and cervical stromal involvement, pelvic and/or paraaortic lymph node metastases at presentation, and higher grade of tumor in the metastatic foci, whereas increased percentage of solid component and lower percentage of mucinous features were marginally associated. Tumors with recurrences only in vagina had different features than tumors that recurred at other sites. The presence of tumor necrosis, MELF foci at the invasive tumor front, and the percentage of solid component and mucinous features could be helpful in grading endometrioid adenocarcinomas, if a 2-tier rather than a 3-tier grading system is accepted in the future.

Dilemmas in distinguishing between tumor and the posttraumatic lesion with surgical or pathologic correlation.

This article discusses the most common diagnostic dilemmas when trying to distinguish between tumor and sports injury or other trauma. Bone tumors frequently occur in the same young active patients who experience sports injuries. If the pain persists longer than expected, imaging studies should be obtained to prevent a delay in diagnosis or an inappropriate arthroscopy. A history of spontaneous fracture or a fracture after minor trauma should raise suspicion for underlying lesion as the cause. Occasionally necrosis and/or hemorrhage within a soft tissue sarcoma is so extensive that only a small cuff of viable tumor tissue is present.

The pattern of myometrial invasion as a predictor of lymph node metastasis or extrauterine disease in low-grade endometrial carcinoma.

The purpose of this study was to examine predictors of lymph node (LN) metastases or extrauterine disease (ED) in low-grade (FIGO grade 1 or 2) endometrioid carcinoma (LGEC) in a multi-institutional setting. For LGEC with and without LN metastasis or ED, each of the 9 participating institutions evaluated patients' age, tumor size, myometrial invasion (MI), FIGO grade, % solid component, the presence or absence of papillary architecture, microcystic, elongated, and fragmented glands (MELF), single-cell/cell-cluster invasion (SCI), lymphovascular invasion (LVI), lower uterine segment (LUS) and cervical stromal (CX) involvement, and numbers of pelvic and para-aortic LNs sampled. A total of 304 cases were reviewed: LN(+) or ED(+), 96; LN(-)/ED(-), 208. Patients' ages ranged from 23 to 91 years (median 61 y). Table 1 summarizes the histopathologic variables that were noted for the LN(+) or ED(+) group: tumor size ≥2 cm, 93/96 (97%); MI>50%, 54/96 (56%); MELF, 67/96 (70%); SCI, 33/96 (34%); LVI, 79/96 (82%); >20% solid, 65/96 (68%); papillary architecture present, 68/96 (72%); LUS involved, 64/96 (67%); and CX involved, 41/96 (43%). For the LN(-)/ED(-) group, the results were as follows: tumor size ≥2 cm, 152/208 (73%); MI>50%, 56/208 (27%); MELF, 79/208 (38%); SCI, 19/208 (9%); LVI, 56/208 (27%); >20% solid, 160/208 (77%); papillary architecture present, 122/208 (59%); LUS involved, 77/208 (37%); CX involved, 24/208 (12%). There was no evidence of a difference in the number of pelvic or para-aortic LNs sampled between groups (P=0.9 and 0.1, respectively). After multivariate analysis, the depth of MI, CX involvement, LVI, and SCI emerged as significant predictors of advanced-stage disease. Although univariate analysis pointed to LUS involvement, MELF pattern of invasion, and papillary architecture as possible predictors of advanced-stage disease, these were not shown to be significant by multivariate analysis. This study validates MI, CX involvement, and LVI as significant predictors of LN(+) or ED(+). The association of SCI pattern with advanced-stage LGEC is a novel finding.

Extramedullary plasmacytoma of the pancreas: a rare entity.

Extramedullary plasmacytomas are plasma cell neoplasms in organs other than the bone marrow. Most are found in the upper respiratory tract. Involvement of the pancreas is rare. We report a case of pancreatic plasmacytoma in association with advanced multiple myeloma.

A 5-year-old girl with an enlarging mass at the elbow.

Pilomatrixoma is a rare benign neoplasm that presents as a solitary, hard, mobile, subcutaneous mass. Pilomatrixomas can be found on any hair-bearing region of the body, with the upper extremity being the second most common location. Pilomatrixomas are common in children, and have a higher frequency in girls. We present a case of left-arm pilomatrixoma in a 5-year-old girl. Surgical excision was curative. Pediatric orthopedic surgeons should be familiar with this benign tumor when evaluating a calcified soft-tissue mass in the extremities of a child.

Pulmonary crystal-storing histiocytosis diagnosed by computed tomography-guided fine-needle aspiration.

Crystal-storing histiocytosis (CSH) is a rare process most often occurring in conjunction with an underlying hematopoietic neoplasm, usually multiple myeloma or low-grade B-cell lymphoma. We report the first case of pulmonary CSH diagnosed by fine-needle aspiration biopsy. A patient with a history of urothelial carcinoma developed a lung nodule, which was evaluated by fine-needle aspiration biopsy. Cytologic examination revealed macrophages with abundant cytoplasmic crystals diagnostic of CSH. Based on this cytologic interpretation, additional clinical laboratory evaluation was pursued and revealed a previously unknown monoclonal serum protein. CSH must be differentiated from other non-neoplastic and neoplastic lesions and when diagnosed, should trigger a search for an underlying lymphoproliferative disorder.