A rare diagnosis of Langerhans cell histiocytosis made on thyroid histology with coexisting papillary thyroid cancer and AVP deficiency.

Summary: A 48-year-old Asian male, presented to the hospital for an elective total thyroidectomy in the context of 6.3 cm thyroid nodule. The fine needle aspiration cytology of the nodule confirmed papillary thyroid cancer (PTC) with some atypical histiocytes. He has a history of idiopathic arginine vasopressin deficiency (AVP-D) and has been taking oral DDAVP 100 µg daily, self-adjusting the dose based on thirst and polyuria. Additionally, he also has a history of recurrent spontaneous pneumothorax. His total thyroidectomy was aborted due to significant intraoperative bleeding, and his admission was further complicated by post-operative hyponatraemic seizure. Thyroid histology revealed the diagnosis of Langerhans cell histiocytosis (LCH), and further investigation with contrast CT demonstrated multi-organ involvement of the thyroid, lungs, and bones. Learning points: Langerhans cell histiocytosis (LCH) is a condition that can affect one or more organ systems, including the pituitary, where it can present as AVP deficiency. Strict monitoring of fluid balance, as well as serial monitoring of serum sodium, is essential in all patients with AVP-D in the perioperative setting. Iatrogenic hyponatraemic seizure is an uncommon but serious complication of DDAVP treatment in hospitalised patients with AVP-D. DDAVP dosing must be carefully monitored. LCH with multisystem involvement is an important mimic for metastatic conditions, and histological diagnosis is essential to guide treatment and prognosis. Although LCH without bone marrow involvement is unlikely to increase the risk of bleeding, its effect on tissue integrity may make surgery more challenging. BRAF-V600E mutation is an important driver mutation and a potential therapeutic target in the treatment of LCH.

Combined pathologic-genomic algorithm for early-stage breast cancer improves cost-effective use of the 21-gene recurrence score assay.

Background: The 21-gene recurrence score (RS) (Oncotype DX®; Genomic Health, Redwood City, CA) partitions hormone receptor positive, node negative breast cancers into three risk groups for recurrence. The Anne Arundel Medical Center (AAMC) model has previously been shown to accurately predict RS risk categories using standard pathology data. A pathologic-genomic (P-G) algorithm then is presented using the AAMC model and reserving the RS assay only for AAMC intermediate-risk patients. Patients and methods: A survival analysis was done using a prospectively collected institutional database of newly diagnosed invasive breast cancers that underwent RS assay testing from February 2005 to May 2015. Patients were assigned to risk categories based on the AAMC model. Using Kaplan-Meier methods, 5-year distant recurrence rates (DRR) were evaluated within each risk group and compared between AAMC and RS-defined risk groups. Five-year DRR were calculated for the P-G algorithm and compared with DRR for RS risk groups and the AAMC model's risk groups. Results: A total of 1268 cases were included. Five-year DRR were similar between the AAMC low-risk group (2.7%, n = 322) and the RS < 18 low-risk group (3.4%, n = 703), as well as between the AAMC high-risk group (22.8%, n = 230) and the RS > 30 high-risk group (23.0%, n = 141). Using the P-G algorithm, more patients were categorized as either low or high risk and the distant metastasis rate was 3.3% for the low-risk group (n = 739) and 24.2% for the high-risk group (n = 272). Using the P-G algorithm, 44% (552/1268) of patients would have avoided RS testing. Conclusions: AAMC model is capable of predicting 5-year recurrences in high- and low-risk groups similar to RS. Further, using the P-G algorithm, reserving RS for AAMC intermediate cases, results in larger low- and high-risk groups with similar prognostic accuracy. Thus, the P-G algorithm reliably identifies a significant portion of patients unlikely to benefit from RS assay and with improved ability to categorize risk.

Long-term survival outcomes of triple-receptor negative breast cancer survivors who are disease free at 5 years and relationship with low hormone receptor positivity.

BACKGROUND: We counsel our triple-negative breast cancer (TNBC) patients that the risk of recurrence is highest in the first 5 years after diagnosis. However, there are limited data with extended follow-up on the frequency, characteristics, and predictors of late events. METHODS: We queried the MD Anderson Breast Cancer Management System database to identify patients with stage I-III TNBC who were disease free at 5 years from diagnosis. The Kaplan-Meier method was used to estimate yearly recurrence-free interval (RFI), recurrence-free survival (RFS), and distant relapse-free survival (DRFS), as defined by the STEEP criteria. Cox proportional hazards model was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We identified 873 patients who were disease free at least 5 years from diagnosis with median follow-up of 8.3 years. The 10-year RFI was 97%, RFS 91%, and DRFS 92%; the 15-year RFI was 95%, RFS 83%, and DRFS 84%. On a subset of patients with oestrogen receptor and progesterone receptor percentage recorded, low hormone receptor positivity conferred higher risk of late events on multivariable analysis for RFS only (RFI: HR=1.98, 95% CI=0.70-5.62, P-value=0.200; RFS: HR=1.94, 95% CI=1.05-3.56, P-value=0.034; DRFS: HR=1.72, 95% CI=0.92-3.24, P-value=0.091). CONCLUSIONS: The TNBC survivors who have been disease free for 5 years have a low probability of experiencing recurrence over the subsequent 10 years. Patients with low hormone receptor-positive cancers may have a higher risk of late events as measured by RFS but not by RFI or DRFS.

Study of the microstructure information of GaAs epilayers grown on silicon substrate using synchrotron radiation.

Williamson-Hall (WH) analysis is a well established method for studying the microstructural properties of epilayers grown on foreign substrates. However, the method becomes inapplicable in specific cases where the structure factor considerations and the presence of anti-phase domains forbid the data acquisition for certain reflections in conventional high-resolution X-ray diffraction (HRXRD) measurements. Here, this limitation is overcome by exploiting the large intensity (25 µW mm(-2)) and high photon energy (15.5 keV) of the X-ray beam obtained from a synchrotron radiation source. The lateral coherence length, vertical coherence length, tilt and micro-strain of GaAs epilayers grown on Si substrate have been successfully measured using the conventional WH analysis. The microstructure information obtained from the conventional WH analysis based on the data acquired at the synchrotron radiation source is in reasonable agreement with the results obtained from atomic force microscope and surface profiler measurements. Such information cannot be obtained on a laboratory-based HRXRD system where modification of the WH method by involving a set of parallel asymmetric crystallographic planes is found to be essential. However, the information obtained from the modified WH method is along a different crystallographic orientation.

Dermcidin isoform-2 induced nullification of the effect of acetyl salicylic acid in platelet aggregation in acute myocardial infarction.

The aggregation of platelets on the plaque rupture site on the coronary artery is reported to cause both acute coronary syndromes (ACS) and acute myocardial infarction (AMI). While the inhibition of platelet aggregation by acetyl salicylic acid was reported to produce beneficial effects in ACS, it failed to do in AMI. The concentration of a stress induced protein (dermcidin isoform-2) was much higher in AMI than that in ACS. Incubation of normal platelet rich plasma (PRP) with dermcidin showed one high affinity (Kd = 40 nM) and one low affinity binding sites (Kd = 333 nM). When normal PRP was incubated with 0.4 µM dermcidin, the platelets became resistant to the inhibitory effect of aspirin similar to that in the case of AMI. Incubation of PRP from AMI with dermcidin antibody restored the sensitivity of the platelets to the aspirin effect. Incubation of AMI PRP pretreated with 15 µM aspirin, a stimulator of the NO synthesis, resulted in the increased production of NO in the platelets that removed the bound dermcidin by 40% from the high affinity binding sites of AMI platelets. When the same AMI PRP was retreated with 10 µM aspirin, the aggregation of platelets was completely inhibited by NO synthesis.

A microfocus X-ray fluorescence beamline at Indus-2 synchrotron radiation facility.

A microfocus X-ray fluorescence spectroscopy beamline (BL-16) at the Indian synchrotron radiation facility Indus-2 has been constructed with an experimental emphasis on environmental, archaeological, biomedical and material science applications involving heavy metal speciation and their localization. The beamline offers a combination of different analytical probes, e.g. X-ray fluorescence mapping, X-ray microspectroscopy and total-external-reflection fluorescence characterization. The beamline is installed on a bending-magnet source with a working X-ray energy range of 4-20 keV, enabling it to excite K-edges of all elements from S to Nb and L-edges from Ag to U. The optics of the beamline comprises of a double-crystal monochromator with Si(111) symmetric and asymmetric crystals and a pair of Kirkpatrick-Baez focusing mirrors. This paper describes the performance of the beamline and its capabilities with examples of measured results.

Pattern of head and neck malignancies in eastern part of Nepal.

The term head and neck refers to the upper aerodigestive tract, the salivary glands, the thyroid, parathyroid glands, the sino-nasal tract and the skin of the head and neck region. Malignancies at these sites are important due to the divergence in their behaviors and prognosis. A retrospective, cross sectional, series of cases were studied to determine the pattern of head and neck malignancies in our department from January, 2005 to July, 2006. A total of 90 cases of head and neck malignancies proven on histopathology were studied. Pharynx 25 (27.78%) was the commonest site involved by cancer. In the pharynx, malignancies at the nasopharyngeal region contributed to the bulk of the tumor constituting 12 (48.00%). Histopathologically, squamous cell carcinoma was seen in 61, (67.77%) subjects. Most of the patients presented in IIIrd or IVth stage of disease. The commonest treatment strategy adopted was surgery with post operative radiotherapy. Nasopharyngeal carcinoma is a major concern in this part of the region.

Primary disseminated extrapulmonary multidrug resistant tuberculosis.

Disseminated tuberculosis is a common mode of presentation of tuberculosis in patients both with and without HIV/AIDS in India. However, primary multidrug resistance in disseminated tuberculosis involving only the extrapulmonary sites in an immunocompetent adult is rare. Here, we report a case of a 19-year-old man who had disseminated tuberculosis involving left pleura, pericardium, peritoneum and intraabdominal lymph nodes. He was initially taking WHO category I antituberculous drugs, but was not responding in spite of 5 months of chemotherapy. Culture of the pleural biopsy specimen grew Mycobacterium tuberculosis which was resistant to isoniazid and rifampicin. He was put on therapy for multidrug resistant tuberculosis,following 24 months of chemotherapyhe had an uneventful recovery.

Abdominal wall endometriosis.

Endometriosis of abdominal wall scar following operation on uterus and tubes is extremely rare. The late onset of symptoms after surgery is the usual cause of misdiagnosis. Scar endometriosis is a rare disease which is difficult to diagnose and should always be considered as a differential diagnosis of painful abdominal masses in women. The diagnosis is made only after excision and histopathology of the lesion. Preoperative differentials include hernia, lipoma, suture granuloma or abscess. Hence an awareness of the entity avoids delay in diagnosis, helps clinicians to a more tailored treatment and also avoids unnecessary referrals. We report a case of abdominal endometriosis. The definitive diagnosis of which was established by histopathological studies.

Infantile myofibromatosis of the craniovertebral junction.

Infantile myofibromatosis (IM) is a rare pathological entity characterized by solitary or multiple nodular skin, soft tissues or bony lesions. Craniovertebral (CV) junction lesions are rare. We report the successful management of a solitary IM involving the posterior elements of the CV junction in a 6-month-old child.

Intraparenchymal pericatheter cyst following ventriculoperitoneal shunt insertion: does it always merit shunt revision?

Intraparenchymal pericatheter cyst is a rare complication of shunt surgery. It occurs as a consequence of increased CSF outflow resistance distal to a patent ventricular catheter. Treatment has traditionally consisted of shunt revision. We report on two such cases managed conservatively. The role of shunt revisions in cases with asymptomatic intraparenchymal pericatheter cyst is debatable.

High-grade infiltrative myxofibrosarcoma in the forearm presenting as acute carpal tunnel syndrome.

Myxofibrosarcoma is one of the most common sarcomas in the extremities of elderly people and is characterized by a high frequency of local recurrence. We report a rare case of high-grade myxofibrosarcoma involving the forearm and presenting as acute carpal tunnel syndrome where absence of a discrete mass lesion and diffuse infiltrative nature precluded early recognition of tumor. To our knowledge, such a presentation with an extreme infiltrative growth pattern in the forearm has not been reported before.

Chondroid syringoma.

Pleomorphic adenoma, or chondroid syringoma (CS), is a rare, benign, skin appendageal tumour. Because of the unremarkable clinical presentation of this rare tumour, the diagnosis is made on microscopic examination. The usual presentation is of an asymptomatic, slowly-growing mass, typically located in the head and neck region. We present a case of a CS located over the forehead of a 32-year-old man. In the evaluation of a middle-aged male patient with a small cutaneous nodule in the head and neck region, chondroid syringoma should also be considered in the differential diagnosis. For such a lesion, excisional biopsy, without destroying the aesthetic and functional structures, is the preferred diagnostic, as well as therapeutic approach.

Rapidly destructive osteoarthritis of the hip joint: a case series.

BACKGROUND: Rapidly destructive arthrosis of the hip is a rare and incompletely understood disorder with scarce literature about variations in natural history within a population. METHODS: A series of cases from North Wales with rapid progressive joint destruction and extensive subchondral bone loss in the femoral head and acetabulum are presented. Radiographic findings mimicked those of other disorders such as septic arthritis, rheumatoid and seronegative arthritis, primary osteonecrosis with secondary osteoarthritis, or neuropathic osteoarthropathy, but none of the patients had clinical, pathologic, or laboratory evidence of these entities. RESULTS: Rapid progression of hip pain and disability was a consistent clinical feature. The average duration of symptoms was 1.4 years. Radiographs obtained at various intervals before surgery (average 14 months) in 18 patients documented rapid hip destruction, involvement being unilateral in 13 cases. All patients underwent total hip arthroplasty, and osteoarthritis was confirmed at pathologic examination. CONCLUSION: The authors postulate that these cases represent an uncommon subset of osteoarthritis and regular review, both clinically and radiologically, are required to assess speed of progression and prevent rapid loss of bone stock without the surgeon being aware. These cases are unsuitable for being placed on long waiting list due to technical difficulties in delayed surgery and compromised outcome following surgery.

Is magnetic resonance imaging (MRI) necessary to exclude occult hip fracture?

The possibility of occult hip fracture in older patients after a fall is a common problem in emergency and orthopaedic departments. Magnetic resonance imaging (MRI) scanning is the best investigation, but is expensive and may be difficult to obtain. The value of various clinical signs to determine which patients are at risk of occult hip fracture has not been reported. We reviewed all patients who had MRI scan for suspected hip fractures but had normal initial X-rays over a 6-year period. We identified 76 patients. Twelve patients were excluded. Two patients had MRI scan for suspected stress fracture and two patients had metastatic fractures. Eight patients had inadequate or untraceable clinical notes. Each patient's personal details, mobility, independence and detail clinical details were recorded. Following case review of 64 patients we excluded 5 patients with associated osteoarthritis of the hip joint, 1 patient with fibromyalgia and 1 patient with pre-existing multiple myeloma. Thirty-five patients had occult proximal femoral fractures. Of them four patients had isolated pubic ramus fractures and five patients had isolated greater trochanter fractures. Twenty-two patients had no fracture. The value of the individual tests was evaluated using Fisher exact and chi square analysis; with Bonferroni correction for multiple comparisons (10 tests) p<0.005 was deemed significant. Pain on axial loading of the limb and pre-fracture restricted patient mobility were both associated with the presence of a fracture (p<0.005). Both factors had identical positive predictive value=0.76, a negative predictive value=0.69 and post-test probability of disease given a negative test=0.30. Predictive values remained the same when both factors were considered together. Patients who were independently mobile before the fall and who do not have pain on axial compression of the limb are less likely to have a fracture, but these signs alone or in combination do not exclude a fracture. The clinical signs investigated cannot distinguish between patients with and without a hip fracture, and MRI scanning is necessary to establish whether some patients have an occult fracture.

Radioprotective and antioxidant activity of fractionated extracts of berries of Hippophae rhamnoides.

Plants are an abundant source of medicinal compounds, some of which are useful in combating free radical-mediated oxidative stress. In the present study, initially two fractions designated REC-1001 (flavonoid-rich fraction) and REC-1002 (flavonoid-poor fraction) of Hippophae rhamnoides were screened on the basis of their reducing power in the aqueous phase. REC-1001 was selected for further study, since it exhibited 27.38 times higher antioxidant activity than REC-1002. REC-1001 also showed significant (P < .05) membrane protection potential at 50 microg/mL, which was attributed to its ability to scavenge peroxyl radicals (64.82 +/- 1.25% scavenging within 1,440 min). A significant (P < .05) difference of 67.02% in free radical scavenging activity at 1,000 ng/mL between REC-1001 and vitamin E demonstrated the extract fraction's worth in radiation protection. Such activities were attributed to the presence of quercetin, isorhamnetin, and kaempferol in this fraction. Further, REC-1001 was found to be nontoxic up to 200 mg/kg of body weight. This research suggests that the REC-1001 fraction of H. rhamnoides extract is a safe and effective antioxidant nutraceutical product.

Intracranial metastases from carcinoma of the cervix.

Uterine cervix carcinoma usually spread by local extension and through the lymphatics to the retroperitoneal lymph nodes. Brain metastases are extremely rare in the course, are usually seen late and have poor prognosis. We report a 49-year-old woman with squamous cell carcinoma of the cervix who developed right parieto-occipital lobe metastasis after three years of treatment of the primary disease. The presenting symptoms of the metastatic disease were hemiparesis, headache, and vomiting. Her hemiparesis improved after surgical excision of the metastasis. Treatment in these cases is mainly palliative but may offer symptomatic relief and improvement in the quality of life.

Methotrexate used in combination with aminolaevulinic acid for photodynamic killing of prostate cancer cells.

Photodynamic therapy (PDT) using 5-aminolaevulinic acid (ALA) to drive production of an intracellular photosensitiser, protoporphyrin IX (PpIX), is a promising cancer treatment. However, ALA-PDT is still suboptimal for thick or refractory tumours. Searching for new approaches, we tested a known inducer of cellular differentiation, methotrexate (MTX), in combination with ALA-PDT in LNCaP cells. Methotrexate alone promoted growth arrest, differentiation, and apoptosis. Methotrexate pretreatment (1 mg l(-1), 72 h) followed by ALA (0.3 mM, 4 h) resulted in a three-fold increase in intracellular PpIX, by biochemical and confocal analyses. After exposure to 512 nm light, killing was significantly enhanced in MTX-preconditioned cells. The reverse order of treatments, ALA-PDT followed by MTX, yielded no enhancement. Methotrexate caused a similar relative increase in PpIX, whether cells were incubated with ALA, methyl-ALA, or hexyl-ALA, arguing against a major effect upon ALA transport. Searching for an effect among porphyrin synthetic enzymes, we found that coproporphyrinogen oxidase (CPO) was increased three-fold by MTX at the mRNA and protein levels. Transfection of LNCaP cells with a CPO-expressing vector stimulated the accumulation of PpIX. Our data suggest that MTX, when used to modulate intracellular production of endogenous PpIX, may provide a new combination PDT approach for certain cancers.