The patient was a 67-year-old man who presented with dysuria. Computed tomography (CT) examination of the upper abdomen revealed multiple swollen retroperitoneal and pelvic lymph nodes and abnormal bone density on January 5th 2015. Positron Emission Tomography-CT (PET-CT) revealed hypermetabolic lesions in the left lobe of the prostate, and multiple bone sites, as well as enlarged lymph nodes of the left neck, supraclavicular region, retroperitoneal, bilateral iliac blood vessels and pelvic left side wall, which were diagnosed as malignant metastasis on February 5th 2015. A prostate biopsy was performed on February 28th 2015, and histologic assessment showed conventional adenocarcinoma with Gleason score 4 + 3 = 7, while serum TPSA level was >100 ng/mL. The clinical course of the patient was summarized in Fig. .
The patient started the treatment with bicalutamide tablets, zoladex and zoledronate on February 28th 2015. His TPSA level dropped to 13 ng/mL after two months of treatment, and he continued on the therapy. However, recurrent disease developed on July 9th 2015, marked by elevated TPSA up to 60 ng/mL. The patient was then switched to the treatment with flutamide and zoledronate. On October 10th 2015, due to persistent increase in TPSA level, the patient was further treated with abiraterone. On February 5th 2016, emission CT showed progression with bone metastases, with TPSA level rising to 150 ng/mL. The patient then started six cycles of systemic chemotherapy with docetaxel and metacortandracin, during which time his TPSA level continued to rise. One month after finishing the systemic chemotherapy, his TPSA level reached 492.3 ng/mL. The patient then received enzalutamide, but by August 22nd 2016, the TPSA level had risen to 644.3 ng/mL.
Considering the poor responses to all currently available therapies, we performed genetic testing on patient’s circulating tumor DNA (ctDNA) from blood using next-generation sequencing (NGS) targeting over 400 cancer-relevant genes. The assay was done using a commercial test. Genomic DNA from the whole blood sample was used as germline control. We detected several genomic alterations known to be associated with prostate cancer; specifically, we identified PIK3CA-Q546K activated mutation with a mutant allele frequency (MAF) of 17%, a TP53-DISCIFP1 fusion (MAF: 12%), 4.1 folds of relative copy number gain of the AR gene, as well as germline BRCA2-G1761X mutation. As a result, the patient started treatment with everolimus, a mTOR inhibitor, for his high MAF of PIK3CA-Q546K mutation. Despite this however, serum TPSA continued to increase slowly 798.9 ng/mL to 1379 ng/mL. On October 27th 2016, CT scan showed progression of multiple lymph nodes metastases, double pleural effusion and appearance of new liver metastases (Fig. ). The patient also developed a fever, shortness of breath and lethargy followed by unconsciousness. The patient was transferred to the intensive care unit (ICU) and underwent transfusion, respirator assisted ventilation and tracheotomy.
Due to prior detection of the BRCA2 G1761X germline mutation and poor physical condition, the patient started on olaparib treatment, 400 mg twice daily by nasal feeding tube, on November 1st 2016; the patient tolerated the dose and his symptoms significantly relieved. On December 26th 2016, CT assessment indicated a partial response (PR) of liver metastases to olaparib (Fig. ). Furthermore, TPSA level was reduced from 1379 ng/mL to 208 ng/mL. Following resolution of fever, shortness of breath, lethargy and unconsciousness, the patient was transferred out of the ICU. On January 22nd 2017, the patient’s blood sample was obtained for ctDNA testing by NGS, which showed that the tumor specific mutations identified before the treatment had significantly decreased (PIK3CA-Q546K, 0.4%; TP53-DISCIFP1 fusion, 0.1%; undetectable copy number gain of AR). After four months of the therapy, his TPSA level continued to fall to 30.65 ng/mL. However, unfortunately, the patient’s disease progressed again after six-month of the treatment, and his ctDNA testing showed that all the previous detected tumor specific mutations elevated to an even higher level compared to pretreatment (PIK3CA-Q546K, 19.9%; TP53-DISCIFP1 fusion, 29.1%; 4.1 folds of relative copy number gain of AR), as well as a newly emerged RB1 single copy number loss. In addition, some other somatic genomic alterations had been found in the third test (Table ).


A 51-year-old black woman with an 18-pack-year smoking history presented to our institution with a 3-month history of a progressively productive cough unresponsive to antibiotics. In addition, she had dyspnea on exertion and a 25-pound weight loss. Her past medical history included a duodenal ulcer resulting in a perforation which required exploratory laparotomy 2 years prior to presentation. Other history included subarachnoid hemorrhage requiring craniotomy with hematoma evacuation roughly 20 years prior to presentation, as well as hypertension. Her family history included her mother being diagnosed with ovarian cancer at the age of 54. The patient is married and worked full-time at the front desk for the past 30 years for a shipping company. She reported alcohol intake of two drinks per occasion twice weekly. She denied the use of any recreational drugs. She denied any environmental exposures. Medications that the patient was receiving at the time of diagnosis included amlodipine and albuterol.
The patient underwent computed tomography (CT) of the chest, which revealed a 5.3 × 6-cm right hilar mass that was occluding the right upper lobe bronchus with narrowing of the SVC. The SVC remained radiographically patent (Fig. ). The patient’s vital signs included afebrile temperature of 37.0 °C, cardiac pulse of 100 beats per minute, and oxygen saturation of 96% on room air. Her physical examination at that time was without any clinical signs of venous congestion. She had no facial plethora and had flat neck veins and no signs of jugular vein distention. She had decreased breath sounds in the right upper and middle lung fields. The skin of the neck and breast was without any pitting or edema. Neurologically, the patient was fully functional with cranial nerves II–XII intact and 5/5 strength in the upper and lower extremities bilaterally. All laboratory test results, including complete blood count and comprehensive metabolic panel, were within normal limits.
Two weeks after the patient’s initial presentation, she was found to have bilateral distended venous jugular veins, with no facial, neck, or breast fullness, which was self-limiting and resolving prior to chemoradiation. She eventually underwent an endobronchial ultrasound with fine-needle aspiration of the right hilar mass along with the contralateral mediastinal station 4L lymph node demonstrating poorly differentiated NSCLC adenocarcinoma in both sites. She then underwent brain magnetic resonance imaging (MRI) and positron emission tomography (PET)/CT (Fig. ), which revealed no evidence of metastatic disease. She was diagnosed with T2bN3M0 stage IIIB lung adenocarcinoma according to American Joint Committee on Cancer 8th edition staging guidelines.
The patient proceeded with expedited radiation planning and treatment, given her radiographic evidence of extrinsic SVC narrowing and physical examination findings of mild and self-limiting jugular venous distention. She received a definitive radiation dose of 60 Gy in 30 fractions concurrent with chemotherapy (cisplatin and etoposide). The patient was simulated in the supine position in a whole-body Vac-Lok ™ (CIVCO Radiotherapy, Orange City, IA, USA) with arms above her head. A four-dimensional (4D) CT simulation was performed using a Philips Ingenuity CT simulation scanner (Philips, Cleveland, OH, USA) to acquire images for treatment planning and assessment of internal target motion. Treatment planning was performed using an Eclipse® treatment planning system (Varian Medical Systems, Pao Alto, CA, USA), and treatment was delivered using a TrueBeam® radiotherapy system (Varian Medical Systems) with two volumetric modulated arc therapy arcs using 6-MV photons. Gross tumor volume (GTV) was contoured on 4D CT images in different phases of the respiratory cycle. An internal target volume was created by the summation of GTV volumes of the different respiratory phases. A 5-mm expansion was used to create the clinical target volume and planning target volume (PTV), respectively. Ninety-five percent of the PTV received at least 57 Gy or 95% of the prescribed dose (Fig. ). Cycle 1 of cisplatin (50 mg/m2 on days 1, 8, 29, and 36) plus etoposide (50 mg/m2 daily on days 1 to 5 and days 29 to 33) started 2 weeks after initiation of radiation therapy. One additional cycle was given after completion of radiation for a total of two cycles of chemotherapy received. The patient did experience some breast swelling and pain that was seen with day 10 of chemotherapy. The event was suspected to be a consequence of the excess intravenous fluids (3 L) coadministered with each infusion of cisplatin. This event was in the setting of the previous stenosis of the SVC resulting from extrinsic compression from the patient’s large right hilar mass. This swelling resolved within 1 week without intervention. The patient also developed esophagitis requiring temporary gastric tube placement necessitating a 5-day hospitalization.
The patient returned to the radiation oncology department for a 3-month posttreatment follow-up visit, for which imaging was ordered. The patient reported that for the past 2 weeks she had developed swelling and pain in her right breast and right supraclavicular region, which were new for her. She also complained of worsening dyspnea on exertion, a 16-pound weight gain over the past 3 months, and intermittent headaches. She denied any facial fullness, orthopnea, or dysphagia. Examination revealed that her vital signs were within normal limits; however, she had obvious compressible swelling of the right supraclavicular region and fullness within the right breast. Chest CT performed 2 days prior to the follow-up visit revealed a remarkable reduction in size by approximately 50% of the treated right hilar mass (Fig. ). However, the SVC was significantly narrowed to completely occluded radiographically, despite being narrowed but patent before treatment. The patient was sent to the emergency department for further evaluation and management. Interventional radiology was consulted, and it was concluded that the patient’s SVC syndrome was likely chronic based on the presence of significant collaterals. No acute intervention was recommended, and she was discharged to home uneventfully.
The patient did have initial radiographic evidence of stenosis of the SVC; however, her initial stenosis did not produce SVC syndrome. The patient did respond very well to treatment, because she had marked reduction of the tumor volume and decrease in the extent of extrinsic compression on the SVC. It was peculiar that she developed SVC syndrome despite her significant treatment response.
We also contemplated intrinsic etiologies for SVC syndrome, including thrombus formation, but this consideration was not confirmed on radiographs. Interventional radiology was consulted and had reviewed her films and did not think thrombus was a likely scenario. There was a concern for recurrent or persistent microscopic disease within the region of the SVC, but there was no fludeoxyglucose avidity in the region on posttreatment PET (Fig. ). The development of an adequate collateral circulation system did indicate the chronicity of venous congestion. The differential diagnosis also included the possibility that the continued stenosis of the SVC was a direct effect of treatment (chemoradiation) because the SVC resided within the PTV receiving the full radiation dose. The SVC was contoured, and dosimetric parameters were as follows: Minimum dose to SVC was 59.74 Gy with maximum dose to SVC 62.36 Gy, and 95% of the SVC received at least 60.35 Gy (Fig. ).
The patient was presented at the multidisciplinary thoracic oncology tumor board, and observation was recommended on the basis of absence of tumor progression and presence of an adequate collateral venous system. Her supraclavicular and breast swelling was self-limited, resolving within 2 weeks after her presentation. Six months after completion of radiation therapy, she underwent PET/CT indicating recurrent thoracic disease and had a fine-needle aspiration biopsy confirming metastatic, poorly differentiated adenocarcinoma in a station 4R lymph node. She was placed on the PD-1 (programmed cell death protein 1) inhibitor nivolumab. Brain MRI was performed for workup, revealing two ring-enhancing lesions in the left frontal and right cerebellum, the largest of which was 2.2 × 1.8-cm in the left frontal lobe. Gamma Knife® (Elekta, Stockholm, Sweden) stereotactic radiosurgery was performed on the two lesions. One year after completion of definitive thoracic radiotherapy, the patient was found to have a new metastatic left parieto-occipital brain lesion that was being worked up at the time of this report. She has not had redevelopment of SVC syndrome.


In February 2014, an 11-year-old male presented with a history of recurrent respiratory tract infections and suspected tuberculosis following a case within his family. On physical examination, he appeared to be in good health. Chest auscultation did not reveal any specific pathological heart or lung sounds. Abdominal objectivity was negative. His parents did not refer any other relevant medical history about him. Tuberculin skin tests resulted positive and a chest X-ray showed a dishomogeneous parenchymal consolidation in the left lower lobe (). Suspecting active tuberculosis, a preliminary CT scan of the thorax was performed showing a heterogeneous consolidation with some cystic masses containing mixed fluid and air in the left lower lobe posterior segment, not in communication with the respiratory tract, and a probable expression of a dysplastic parenchymal area ( and ). These findings were suggestive of pulmonary sequestration, including a differential diagnosis of congenital pulmonary airway malformation, because of the presence of a cystic component within the consolidation. The injection of contrast medium showed an artery arising from the descending thoracic aorta that divided into two 1.2 cm after its exit, with both branches extending to the dysplastic area; therefore, a diagnosis of intralobar sequestration with associated aspects of bronchial atresia was made; superinfection and trapping of contiguous parenchyma coexisted. Just below the emergence of the previously anomalous vessel, another artery was detected that crossed the midline to achieve a healthy parenchyma in the right pulmonary base, configuring a pattern of aberrant systemic artery feeding a normal lung (–). Other congenital anomalies that appear to be related to pulmonary sequestration were absent; in particular, pulmonary venous drainage was regular through the pulmonary veins, there was no communication between the bronchus and the oesophagus, and no diaphragmatic defects or other gross pulmonary anomalies were identified either. Our patient responded well to antitubercular antibiotic therapy and his clinicians, together with his family, decided to keep him under control with clinical follow-up, avoiding surgery for the moment.


In August 2006, the remains of a 38-year-old female were discovered in Pachangnoi Subdistrict (N 19°19′24.24″; E 100°27′17.28″), Pong District, Phayao Province, northern Thailand (), and transferred to the Department of Forensic Medicine, Faculty of Medicine, Chiang Mai University. Forensic autopsy revealed the impact of blunt and sharp forces on the head and the abdomen. The bloated body was infested by fly maggots. Two blow flies, C. megacephala and C. villeneuvi, and one muscid species belonging to the genera Hydrotaea were identified. The minimum post-mortem interval (PMImin) was estimated to be six days, based on the developmental rate of C. megacephala. However, identification of one fly species could not be achieved due to the limited information on fly larvae morphology of species of forensic importance in Thailand at that time.
Initial macroscopic examination of the fly larvae sampled showed two groups of maggots: third instars of non-hairy maggots and third instars hairy maggots. The non-hairy maggots were identified as the blow fly, C. megacephala and the muscid Hydrotaea sp. The hairy maggots were mainly identified as third instars of the blow fly, C. villeneuvi []. Interestingly, we sampled about 20 third instars specimens that were unfamiliar to us. All larvae sampled were preserved in 70% alcohol. The largest larva was measured using Vernier calipers. In 2017, we decided to reanalyse the unidentified larvae of this case. Some specimens were cut using a sharp blade at two sites, across the third thoracic segment and across the middle of the eighth abdominal segment, to examine the cephaloskeleton and posterior spiracle, respectively. The anterior and posterior ends were transferred into a small eppendorf tube consisting 10% KOH. These tubes were then put into a beaker (half-filled with boiling water) which was placed on a hotplate (Barnstead/Thermolyne, Model: SP46920-26, USA) for 10 min. Specimens were washed twice with distilled water. To remove the alcohol, specimens were placed in Cellosolve (ethylene glycol monoethyl ether) and left for 5 min. The specimens were then transferred onto a glass slide and one drop of Euparal® was added. Specimens were arranged in their appropriate positions and covered with a cover slip. Prepared anterior and posterior ends were examined and photographed under a light microscope (Olympus CX41, Tokyo, Japan, with Olympus DP22 digital camera). For photographing, the focus stacking was shot by taking a series of images with the same composition and gradually changing the area of sharp focus. The number of pictures taken depended on the thickness of the specimen. For preserved larvae, stacking pictures were taken using a Nikon D7100 digital camera with a Nikkor lens Af-s macro 60 mm f2.8G. Each picture was merged in the program Helicon Focus 6.6.0 using method C (pyramid stacking). Terminology for general larval morphology followed Courtney et al. [], for peripheral tubercles of larvae followed Liu and Greenberg [] and for modifications of larval cephaloskeleton followed Szpila et al. [].
The largest specimen was 12.8 mm long. The prominent features are the protuberant tubercles encircling body segments, of which the prominent tubercles originate from the first abdominal segment and are present until the eighth abdominal segment ((A–C) and (A)). Spine bands between segments are obvious in the thoracic segments, with the most prominent between the first and second thoracic segments ((A)). These spine bands between thoracic segments are relatively sclerotized ((A,B). However, spine bands between the abdominal segments are unnoticeable ((C)).
A very distinct ultrastructure of the surface integument is seen on the body surface, which is covered with dense variable size of denticles ((A–C) and (B)). The anterior spiracle consisted of 9–11 lobes (n = 13) arranged in a single row ((B,C)). The cephaloskeleton ((C)) has large and heavily sclerotized mouthhooks, curved downwards. The posterior base of the mouthhooks is large and broad. An accessory sclerite is moderately sclerotized, adjacent to the base of the mouthhooks. The dental sclerite is apparent, curved backward apically and connected to the base of the mouthhooks. An intermediate sclerite is present. The parastomal bar is slender and slightly curved upward apically. The dorsal bridge is slender apically and bent downward, with the same length as the anterior margin of parastomal bar. The dorsal cornua, vertical plate and ventral cornua are heavily sclerotized. The dorsal cornua are much longer than the ventral cornua. The ventral cornua have an opening or window ((C), arrow).
The posterior end of the third instar shows six prominent pairs of tubercles along the peripheral rim of the eighth abdominal segment ((A,C) and (E)), of which all six pairs (inner dorsal, median dorsal, outer dorsal, outer ventral, median ventral and inner ventral tubercles) are almost equally in their protuberance. Viewed posteriorly, there is a remarkably sculpture encircling the posterior spiracles and adjacent to these tubercles ((E)). Higher magnification of the posterior spiracles revealed thick, heavily sclerotized complete posterior spiracular peritremes enclosing three spiracular slits ((F)). The button (or ecdysial scar) is indistinct ((F), arrow).
A key for identification of the third instar of blow flies of forensic importance in Thailand is provided as follows:
Abdominal segments with large, elongate tubercles ((A) and (A))…………2 Abdominal segments lacking large, elongate tubercles ((B))…………3 Tubercles bear numerous small spines at tip ((B)); anterior spiracle with 9–12 lobes; posterior spiracle large, with heavily sclerotized incomplete peritreme ((C))………C.rufifacies (Macquart) Tubercles bear numerous small spines throughout ((D)); anterior spiracle with 13–15 lobes; posterior spiracle large, with heavily sclerotized incomplete peritreme ((E))…………C.villeneuvi Patton Abdominal segments bear protuberant tubercles ((A–C)); anterior spiracle with 9–11 lobes; six prominent pairs of tubercles along the peripheral rim of the eighth abdominal segment ((D,E)); posterior spiracle large, with moderately sclerotized complete peritreme ((F))………C.chani Kurahashi Abdominal segments without protuberant tubercles…………4 Peritreme incomplete………5 Peritreme complete…………7 End of upper peritreme gradually enlarged ((A)); spines between the first and second thoracic segment large, multipointed ((B)); some specimens with brown patch on dorsal integument ((C)), but some not ((D))……………C.nigripes Aubertin End of upper peritreme normal; never with brown patch on dorsal integument………6 Anterior spiracle with 4–6 lobes; posterior spiracle large, with moderately sclerotized incomplete peritreme ((A)); spines between the first and second thoracic segment large, single point ((B))…………C.bezziana Villeneuve Anterior spiracle with 9–12 lobes; posterior spiracle large, with moderately sclerotized incomplete peritreme ((C)); spines between the first and second thoracic segment moderate, single or multipointed ((D))…………C.megacephala (F.) With prominent outer ventral tubercle at the rim of the eighth abdominal segment; anterior spiracle with 9–12 lobes; posterior spiracle lightly sclerotized with incomplete peritreme ((A)); spines between the first and second thoracic segment large, arrange singly or rows ((B)); accessory sclerite heavily sclerotized ((C))…………Lucilia sinensis Aubertin Without prominent outer ventral tubercle at the rim of the eighth abdominal segment…………8 Posterior spiracle small, lightly sclerotized ((D)); anterior spiracle with 3–6 lobes; spines between the first and second thoracic segment small, arranged mostly in group or row ((E)); accessory sclerite unsclerotized ((F))…………L.cuprina (Wiedemann) Posterior spiracle large, moderately sclerotized ((G)); anterior spiracle with 5–9 lobes; spines between the first and second thoracic segment small, arranged mostly in rows ((H)); accessory sclerite unsclerotized ((I))………L.porphyrina (Walker) Specimens of larvae used in the key were from laboratory colony and/or forensic death scenes, by which adults were confirmed by morphology.
Some samples of these unknown species have been preserved in 70% ethanol since 2006 with the label of date and time of collection. To confirm the state of the species, molecular identification was performed in 2017 using these samples kept for more than 10 years.
For DNA extraction, polymerase chain reaction (PCR) amplification and DNA sequencing, the genomic DNA was extracted from one larva according to the dilution protocol of the Phire Animal Tissue Direct PCR Kit (Thermo Scientific). After measuring the DNA concentration, 100 ng/mL of the extracted DNA was subsequently used for PCR reaction.
DNA amplification was performed according to the PCR protocol of the kit. Partial COI sequences were amplified using the primers TY-J-1460 (5′-TACAATTTATCGCCTAAACTTCAGCC-3′) and C1-N-2800 (5′-CATTTCAAGCTGTGTAAGCATC-3′) []. Cycling condition was initially denaturation at 98 °C for 5 min, followed by 40 cycles of denaturation at 98 °C for 5 s, annealing at 61.7 °C for 5 s, extension at 72 °C for 30 s, followed by extension at 72 °C for 1 min. PCR products were electrophoretically separated in an 1% agarose gel, stained with RedSafe™ (Intron Biotechnology). For sequencing, the unpurified PCR products were sent to the First BASE Laboratories Sdn Bhd (Selangor, Malaysia).
To perform the sequence alignment and phylogenetic analysis, the obtained DNA sequences from both directions were edited and assembled using BioEdit software version 7.0.9.0. []. For the highest similarity search, the sequence was compared with the available sequence database via a Basic Local Alignment Search Tool (BLAST) search at the National Center for Biotechnology Information (). Using MEGA6 software [], neighbour-joining tree [] was constructed using Kimura 2-parameter (K2P) model [] with 1 000 bootstrap replications. Additionally, reference sequences retrieved from GenBank covering a fragment length equal or longer than ours were aligned, trimmed and added to the analyses.
Based on the BLAST search, our larval sample collected from the human corpse was 100% identical to C. chani (GenBank accession no: KR921606), confirming to be C. chani, based on 1 205 bp of COI (). Additionally, analysis of phylogenetic analysis revealed that C. chani was grouped within C. megacephala, C. pinguis, C. thanomthini, C. bezziana and C. nigripes [].


A 45-year-old female presented to Endocrinology clinic for evaluation of weight gain. During the interview, she reported polyphagia and polydipsia. Her past medical history was significant for hypertension, hyperlipidemia, obesity, sleep apnea, peripheral vascular disease and mood disorder. She was also diagnosed with mild mental retardation as a child. She experienced her menarche at the age of 13 and had regular periods. She was living in a group home and was not married or had kids. The patient’s height was 4 feet 11 inches and she had a body mass index (BMI) of 40. Physical examination was significant for short stature, facial dysmorphism with prominent forehead, upslanted eyes, flat nasal bridge and a thin upper lip. Extremity examination revealed short 4th and 5th metacarpal and metatarsal bones bilaterally.
Secondary causes of obesity and AHO were considered in differential diagnosis. On blood testing the patient’s calcium, phosphate and parathyroid hormone (PTH) levels were normal. Cortisol, thyroid stimulating hormone (TSH), and free thyroxine (FT4), follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels were all normal. The patient was sent for genetic testing with a presumed diagnosis of PPHP. Karyotype test showed terminal deletion of the long q-arm of one chromosome 2 in all analyzed cells-46, XX, del (2)(q37.1), consistent with BDMR.
Figure shows round face of our patient and Figure shows the brachydactyly of third and fourth fingers.


Case 1: Ms. K, a 70-year-old woman who immigrated to the US at the age of 53, began complaining of watery eyes, chest pain, lower back and joint pain, leg cramps, and weakness. She harbored delusions of being afflicted with high blood pressure, uterine cancer, blood cancer with bone metastasis, brain cancer with extensive metastasis, and believed that her brain was "shrinking."
She first visited a cardiologist in 2013, complaining of intermittent episodes of chest pain over six months. An electrocardiogram (EKG) at the time showed bradycardia, a first-degree atrioventricular (AV) block and a left bundle branch block. At her sixth visit with the cardiologist, she mentioned non-specific somatic complaints, which she said were because of a "hematological problem." Five months later, she was evaluated for “renal hypertension” and imaging studies showed a renal cyst. While she did not follow up with the nephrologist, she continued to make hospital visits for persistent chest pain. A full medical workup was completed and found to be normal at every ER visit. Medical records from a prior ER visit revealed that she had made claims that the Russian military entered her residence and stole her urine, resulting in the disappearance of her kidneys.
Ms. K was brought to the ER by the police after she showed up with a can of gasoline and matches at her primary doctor's office and threatened to burn it down. She was irate and claimed that all of her doctors, in the US and in her home country, were concealing the fact that she had oncological issues. She vehemently denied any psychiatric illness, stating that these diagnoses appeared on her records as a result of a rumor started by an envious former colleague. She explained that because she had been a former practicing neurologist in her home country, she was confident that she had cancer. Upon repeated questioning, she admitted that in a final bid to receive the medical attention that she was rightfully due, she had devised the plan to burn down the doctor’s office.
While in the psychiatric inpatient unit, she remained somatically preoccupied and reported abdominal pain, lower back pain, and weakness, which she attributed to the metastatic spread of uterine cancer to her spine. Radiological imaging confirmed no evidence of uterine cancer, though a thickened endometrium was reported with recommendations for further testing by tissue sampling. Because Ms. K’s ability to make rational and reasonable decisions about her psychiatric and medical treatment was compromised by her delusions, the team sought and was granted a court order allowing them to treat her over her objection.


Case 2: Ms. M was a 64-year-old woman whose medical history was significant for several visits to different doctors seeking treatment for somatic complaints, including progressive blindness, headaches, hypertension, pelvic pain, vaginal swelling, lower extremity pain, and swelling. She was brought into the ER from her primary care doctor’s office for complaints of pelvic and leg swelling, which she attributed to poor diet. She expressed great concern over her problems being persistently ignored at all ERs she had been to.
Ms. M was found hiding in the closet of a primary care doctor’s office early in the morning before it was open for business. Apparently, she saw the janitor approaching and got scared. When the police were able to get into the closet, they discovered a knife, a pair of scissors, and a child's toy phone (which she had been using to call her doctor) in her possession. She revealed that she had gone to the office out of exasperation because she believed that no doctors were listening to her concerns.
She informed the team of the inpatient psychiatric unit about her history of hypertension and migraine headaches. All radiological imaging was negative for structural problems. She became increasingly irritable and accused the treatment team of not having her best interests in mind. She refused meals because she was convinced that they were poisoned and laced with psychiatric medication. Her persistent complaint of pelvic swelling and subsequent physical examination prompted a gynecology consult, which revealed a vaginal prolapse. She became fixated on the problem and demanded an immediate resolution of the issue. She continually refused psychiatric medications, interviews, blood pressure checks, and blood draws. The treatment team sought a court order and the judge ruled in favor of administering medications against her will, and she conceded and started taking them. In the days ensuing, her insight gradually improved, she became much calmer and less argumentative, and even accepted increased dosages, affirming that she understood the indication. While her somatic complaints did not dissipate, she improved to a point where she was deemed to no longer be a danger to herself or others and she was discharged.


A 41-year-old male was referred to our department for possible neurosurgical intervention following magnetic resonance imaging (MRI) that showed a lesion suspected to be an esthesioneuroblastoma (Figure ). He presented with a several-month history of intermittent headaches and loss of smell. He also reported near fainting episodes and slight unintentional weight loss over the same time period. The review of symptoms was negative for epistaxis and visual deficits, and neurological examination showed no abnormalities other than his aforementioned anosmia.
His MRI showed a large mass with both cystic and heterogeneously enhancing solid components extending from the region of the mid-left ethmoid air cells superiorly into the anterior cranial fossa, left frontal lobe, and left basal ganglia, causing mass effect on the left lateral ventricle and a midline shift.
The tumor was resected through a bifrontal craniotomy; the original surgical plan involved a formal craniofacial resection via a combined neurosurgical-otolaryngological approach. Intraoperatively, the tumor was found to have a clear arachnoid plane with no gross attachment to the surrounding dura or brain, and frozen section did not reveal any atypia, increased mitoses, or other aggressive features. Therefore, we elected to forgo a full craniofacial resection. Gross total resection was achieved and the skull-based repair was completed with a harvested pericranial flap and watertight dural closure. The patient awoke at his neurologic baseline and was discharged home on postoperative day one.
On permanent section, the lesion was determined to be a World Health Organization (WHO) Grade I schwannoma (Figures -). Surgical pathology demonstrated S-100 protein immunohistochemical stain positivity and was negative for meningioma markers (progesterone receptor (PR) and anti-epithelial membrane antigen (EMA)). The patient had an uneventful postoperative course and experienced no significant headaches, neurologic symptoms, cerebrospinal fluid (CSF) rhinorrhea, or other notable complications.
Literature review
We identified 10 cases of nasoethmoid schwannoma with intracranial extension in the medical literature (Table ). These lesions occurred in patients from age 24 to 50, with the vast majority presenting by age 40. There appears to be no association with gender. Although specific symptoms depend on the location and size of each tumor, most patients displayed a gradual onset of anosmia with increasing tumor growth and extension. Headache and visual deficits were also commonly seen among symptomatic patients. Bifrontal craniotomy was the most frequently utilized surgical approach for tumor resection, although several cases required a combined intracranial and transfacial approach. Gross total resection was achieved in all cases except one; the exception was a malignant tumor, which was neither encapsulated nor easily separable from the surrounding anatomical structures like the other benign tumors. Among articles reporting postoperative complications, CSF rhinorrhea was seen in three patients, as well as a variety of other complications associated with the unique locations and operative courses of individual lesions (Table ). Two patients, including the case presented in this paper, had no postoperative complications.


A twenty-six-year-old male presented to our emergency department after sustaining a self-inflicted gunshot wound to the abdomen thirty minutes prior to arrival. His past medical history was noted for bipolar disorder. Upon arrival by Emergency Medical Services (EMS), trauma code was activated. On primary survey, patient was hemodynamically unstable. His blood pressure was 90\65 mmHg, heart rate was 121 beats\minutes, and was maintaining his airway with a saturation of 98% on oxygen face mask with good bilateral air entry. He scored 14\15 in Glasgow Coma Scale (GCS), with bilaterally reactive three-millimeter pupils. Examination of the abdomen showed an entry wound midline, about ten centimeters above the umbilicus with no exit wound on logrolling. Focused Assessment with Sonography for Trauma (FAST) was positive for free fluid in Morrison’s pouch, spleno-renal and suprapubic regions. Patient received two liters of normal saline, two units of Packed Red Blood Cells (PRBC) class I, and one gram of Tranexamic acid. After that, the patient was intubated, with trauma line inserted, and immediately pushed to the Operating Room (OR) as first-level emergency case within fifteen minutes. A midline exploratory laparotomy revealed large amount of hemoperitoneum and active bleeding which was controlled by packing all four-quadrants of the abdomen. One bleeder was identified to be coming from the lesser curvature, most likely from the right gastric vein, which was controlled with a figure-of-eight PDS stich. After opening the lesser sac, there was another expanding hematoma posteriorly. Decision was made to kocherize the duodenum to reach the retroperitoneum, where another two bleeders were identified. One of which was from one of the supra-renal tributaries of the Inferior Vena Cava (IVC) at its lateral wall and the other coming from the SMV just inferior to the pancreas (). The site of SMV injury was in the mid-third point, around 3–5 cm from the IVC. The SMV injury was less than 1 cm in size, with a low-flow bleeding. Therefore, we cleared the bleeding vessel above and below the injury, identified the lesion, applied proximal and distal pressure, and a couple of stiches were taken in a figure-of-eight manner using PDS sutures (, ). Then, we released proximal and distal pressure, and hemostasis was effectively achieved with our stitch. Multiple pellets were found, and we were able to remove around seventy-five of them. Exploration of major vessels using Mattox and Kocher maneuvers revealed a pocket of pellets next to the aorta, without other injuries (). Therefore, we proceeded with irrigation and partial closure of the abdomen with a Bagota’ bag. A total of eight units of PRBC and three units of Fresh Frozen Plasma (FFP) were given during the operation. The patient was shifted to the Surgical Intensive Care Unit (SICU), and post-operative CT scan and CTA run-off were done, showing patent vessels and no extravasation of contrast, with only minimal irregularity at the IVC injury site. The patient was taken back to the OR in less than forty-eight hours for a second-look laparotomy, which showed no active bleeding or other injuries. There was a concern for bowel viability, however, there was good supply as there was no ischemia or dusky bowel. Therefore, the packs were removed, irrigation and permanent closure of the abdomen were performed, and patient was sent back to the SICU. Two days later, the patient was extubated and started on oral feeding. Psychiatry consultation was made, and the patient was started on Olanzipine and Valproic acid. Close observation of the patient’s safety was ensured, with suicide precautions and one-to-one monitoring. The patient was then transferred to the general surgical ward the following day where he was observed daily by both the psychiatry and surgery teams. After two weeks, the patient was transferred to a local hospital specialized in mental health. Last follow up of the patient was in the surgery clinic, after one month from his first presentation, where he was in good health with no active issue.


A 22-year-old woman with no general health problems was referred by her dentist to the Endodontic Department, School of Dentistry, Feira de Santana State University. The patient complained of painful swelling on the mucosa over the maxillary right lateral incisor. Clinical examination revealed a sinus tract (Fig. A), and the tooth did not respond to cold thermal test (Endo-Frost; Roeko, Langenau, Germany), as well as presented hypersensitive response to percussion and palpation, although adjacent teeth all responded within normal patterns. Periodontal probing depths were normal (< 3 mm).
Radiographic examination revealed a large periradicular radiolucency, an open apex and a complex canal anatomy with type II DI (Fig. B). Cone-beam computed tomographic (CBCT) scan was requested as a complementary examination to avoid possible complications during treatment (). Sagittal and axial CBCT images showed the invagination extending beyond the cementoenamel junction, reaching the pulpal space and periapical radiolucency disrupting the bone cortical palatal (Fig. 1C,D). The patient was informed of the diagnosis and the need for root canal treatment.
Root canal treatment was performed under local anesthesia using 2% lidocaine with 1:100,000 epinephrine (Nova DFL; Taquara, Rio de Janeiro, Brazil). A rubber dam was placed, and the access cavity was performed using diamond burs in high-speed rotation. The invaginated tissue was carefully removed using an ultrasonic tip (E3D; Helse Dental Technology, São Paulo, Brazil) (Fig. A) with the aid of a dental operating microscope (Alliance; São Carlos, São Paulo, Brazil). The canal was copiously irrigated with 2.5% NaOCl and the working length (WL) was established electronically with an apex locator (Root ZX; J Morita USA Inc, Irvine, CA) using a size 50 K-file (Dentsply Maillefer, Ballaigues, Switzerland). The XP-endo Finisher instrument was placed in a contra-angle hand piece (VDW, Munich, Germany), cooled (Endo-Frost), removed from the plastic tube and inserted in the canal without rotation. Then, the rotation was initialized (800 rpm and 1 Ncm), and the instrument was activated for 1 min using a slow and gentle 7-8 mm lengthwise movements up to the WL. The instrument was brushed against the sidewalls of the canals during the instrumentation (Fig. B,C). This cycle was repeated three times. The canal was irrigated with 5 mL of 2.5% NaOCl using a 30-G NaviTip needle (Ultradent Products Inc, South Jordan, UT, USA) up to 3 mm short of the WL after each cycle. The smear layer was removed by rinsing the canal with 2 mL of 17% EDTA for 3 min followed by 5 mL of 2.5% NaOCl. Finally, a 3 mL rinse with bidistilled water was used in the final irrigation to flush out the NaOCl. After that, the canal was dried with sterile absorbent paper points (Dentsply Maillefer), filled with calcium hydroxide (Ultracal; Ultradent Products Inc), and sealed with a temporary filling material (Cavit; 3M ESPE, Seefeld, Germany).
One month later, at the second appointment, the tooth was asymptomatic and the sinus tract had disappeared. After access, the canal was copiously irrigated with 2.5% NaOCl and another cycle using the XP-endo Finisher instrument was performed to remove the calcium hydroxide. An apical plug of mineral trioxide aggregate (MTA) Repair HP (Angelus Dental Solutions; Londrina, Paraná, Brazil) with approximately 3 mm was performed. The remaining pulp space was then carefully filled with gutta-percha (VDW) and AH Plus sealer (Dentsply De Trey, Konstanz, Germany) using the continuous wave of condensation technique. The continuous wave of condensation technique was performed using a fine tip plugger of the System B, which was heated to 200°C and taken to a depth 6-mm short of the apical plug. The tip was allowed to cool for 15 s, and a single burst of heat was applied for 1 s and the tip was removed. The canal was completely backfilled with Obtura II gutta-percha (Spartan, Fenton, MO) with the unit set at 200°C.The access was sealed with a temporary filling material (Cavit), a final radiographic was performed (Fig. D) and the patient was referred to her general dentistry. The patient returned for clinical and radiographic examinations after six (Fig. A) and fourteen months (Fig. B). Another CBCT scan was performed after fourteen months (Fig. C,D). Periapical radiograph and CBCT images revealed evidence of advanced healing and periapical repair.


A 62-year-old man was diagnosed with end-stage renal disease 20 year ago, and a native AVF was created at the left wrist for hemodialysis treatments. One year later, the patient received his first kidney transplant in the right iliac fossa and took a combination of immunosuppressive medications (including azathioprine, cyclosporin A, and corticosteroids). After that, the AVF was abandoned. Fifteen years ago, physical examination found that the AVF was occluded. At 6 years after renal transplantation, the patient suffered from lower extremity edema and was diagnosed with acute kidney transplant rejection based on renal biopsy. The failed transplanted kidney was surgically removed, and the patient received his second kidney transplant in the left iliac fossa. After the transplantation, the patient continued immunosuppressive therapy, with serum creatinine levels ranging between 120 and 130 μmol/L.
Eighteen months ago, the patient presented with orthopnea, nausea, and vomiting, and was admitted to the Department of Nephrology. On physical examination, there was no thrill or pulse over the AVF and no bruit on auscultation. Vascular ultrasound examination revealed the patent brachial (Fig. , blood flow: 101 mL/min) and radial (Fig. , diameter: 1.1 mm) arteries and the totally occluded AVF with no blood flow (Fig. ), which was illustrated in the skin (Fig. ). Serum creatinine concentration was 853 μmol/L and blood urea nitrogen was 34.1 mmol/L. The patient was diagnosed with renal allograft failure, and immediate hemodialysis restart was required. To promptly prepare a vascular access, we decided to attempt percutaneous revascularization of the patient’s chronically occluded AVF. Since we already had successful experience in treating stenotic and acutely thrombosed AVFs with ultrasound-guided transluminal angioplasty, we performed the revascularization under ultrasound using the Apollo 500 system (Toshiba, Tokyo, Japan), equipped with a 9–18 MHz linear transducer probe. The AVF was retrogradely punctured with a 22-G needle, and a 6-Fr sheath (Terumo, Tokyo, Japan) was retrogradely inserted into the fistulous vein (Fig. ). At first, a 0.014-in. Hi-Torque BMW Elite guidewire (Abbott Vascular, Santa Clara, CA, USA) was advanced to the lesion, but failed to cross the chronic total occlusion lesion at the AVF after switching the wire tip direction several times (Fig. ). An additional movie file shows this in more detail (see Additional file ). With the support of a 6-Fr angiographic catheter advanced to the occlusion site, the guidewire was carefully and gradually inserted the chronic total occlusion lesion and successfully crossed the lesions at the fistula, anastomosis, and the radial artery, and parked in the radial artery (Fig. ). An additional movie file shows this in more detail (see Additional file ). Subsequently, the radial artery was dilated with a 4.0 mm × 20 mm TREK balloon (Abbott Vascular) three times at 4, 8, and 12 atm (Fig. ), and the occluded lesion was dilated at 12, 18, and 20 atm. Then, further dilation of the lesion was performed with a 6.0 mm × 40 mm TREK balloon (Abbott Vascular) three times at 12 and 20 atm (Fig. ). The procedure took 54 min. After the dilation, the diameter and blood flow of the radial artery were 3.3 mm and 138 cm/s, respectively; and the cephalic vein diameter and blood flow were 2.9 mm and 251 cm/s, respectively. The diameter of the anastomose site was 3.2 mm (Fig. ).
The revascularized AVF was used for hemodialysis after the intervention and remains patent for as long as 18 months. At the 2-, 6-, and 18-month follow-ups, the anastomose site diameter and AVF blood flow were 3.8 mm and 340 cm/s (Fig. and ), 3.8 mm and 291 cm/s (Fig. and ), and 0.8 mm and 255 cm/s (Fig. and ), respectively. Although the anastomose site was stenotic at 18-month visit, the proximal AVF segment was normal with a diameter of 4.5 mm.


Patient 1 is a girl aged 5 years and 9 months, the first child of a healthy nonconsanguineous couple. Her psychomotor milestones were profoundly delayed, with raising head at 8 months, sitting alone at 1 year old, and still unable to walk by herself at 5 years and 9 months. Poor eye contact, hand clapping, hand wringing and bruxism were observed at 1 year old, followed by deterioration of hand skills. Epileptic attack occurred at 20 months old, and she responded to valproate (VPA), oxcarbazepine (OXC), and topiramate (TPM) combined therapy. Seizure free was achieved at 5.5 years old. EEG demonstrated spike-slow waves at right medial and posterior temporal, with generalization. MRI (1 year old) revealed enlargement of frontal subarachnoid space. Above manifestations led to the diagnosis of typical RTT. However, mutational analysis of MECP2, CDKL5 and FOXG1 was negative. Through this study, a de novo missense MEF2C mutation, c.48C > G, p.Asn16Lys, was identified, which was a novel mutation.


Patient 2 is a 2.5 years old girl presented with RTT-like ID. she displayed profound psychomotor retardation, with controlling head at 5 months, sitting alone at 8 months. She remained unable to walk independently and still had no speech at 2.5 years old. She developed stereotypic hand movements and bruxism at 2 years of age. No seizure was reported, but there was epileptiform discharge on EEG at age of 2 years. Brain MRI revealed high T1 and T2 signal at posterior horn of bilateral ventricle. A nonsense mutation, c.565C > T, p.Arg189*, of MEF2C was discovered, a known disease causing mutation ().


Patient 3 is a 23-month-old girl who presented with RTT-like features. Feeding difficulties caused concern at 3 months of age. No epilepsy was observed, though she had medical history of febrile convulsions at 9 months old. There was significant delay in her developmental milestones, without obvious retrogression. She could sit alone at 1 year old, and walk at 23 months of age, with abnormal gaits. Unmeaningful language began at 12 months. She also presented with poor eye contact, stereotypic actions, breathing disturbance, and sleeping abnormalities. She suffered from recurrent respiratory infections frequently after 15 months of age. MRI revealed hypomyelination at 1 year and 10 months of age. A novel nonsense mutation, c.334G > T, p.Glu112*, in MEF2C was identified.


Patient 4 was a boy aged 7 years and 8 months. He achieved the gross motor developmental milestones somewhat delay, with rising head at 1 year old, sitting alone at 1 year and 2 months, and walking at 1.5 years. Lack of speech was another problem, that he still cannot speak a single word so far (7 years and 8 months). He was always immersed in his own world, showed little interest to the others, and lacked eye-contact. Febrile seizures attacked at 1 year, which turned into afebrile seizures at 2 years old. Partial seizures occurred 1~ 2 times per month, lasted few minutes to more than half an hour. The epilepsy was fever-sensitive. VPA was used at 2.5 years of age, and no seizures occurred after 4 years of age. EEG at 2.5 years displayed (multi-) spike and slow waves at right occipital region, with slow rhythm on the background. MRI at 3 years of age was normal. A novel mutation, c.403-1G > T, of MEF2C was identified, which arose de novo.


An 82-year-old woman with severe cognitive impairment (Mini Mental State score 14/30) was admitted in our department because of anorexia, weight loss, fatigue, and mild night fever. She complained of chronic knee and wrist pain. On clinical examination, she had a left pleural effusion without crackles or clinical signs of heart failure. There was no joint effusion, nor synovitis. Biological data were as follow: C-reactive protein: 59 mg/L (N < 5), White blood cell count: 3.3 G/L with 8.2% eosinophils, hemoglobin was 10 g/d L, platelet count was 150 G/L. A High contrast thoraco-abdomino-pelvic CT-scan showed multiple millimeter lymph nodes in the mediastinum, and a left pleural effusion without parenchymal lesion. A thoracocentesis (200 mL) revealed an exudate with 3065 M/L of predominantly lymphocyte-white blood cells (59%) with eosinophilia (20%). Direct cytological examination showed Hargraves cells, that is, LE cells, characterized by homogenous nuclear material (hematoxylin body) encompassed by neutrophils. No malignant cells were found, and pleural fluid culture was negative for Mycobacterium tuberculosis. A few days later, antinuclear antibodies (ANA) with homogeneous pattern were found with a titer of 2560 (N < 80) in the serum, and 5000 in the pleural effusion. Anti-nucleosome antibodies were also present (91 UI/L [N < 20]), without antiphospholipid antibodies. There was no hypocomplementemia. Search for HIV, CMV, EBV, HBV, HCV was negative, leading to the diagnosis of systemic lupus erythematosus according to ACR criteria. Hydroxychloroquine (400 mg/d) and prednisone 0.5 mg/kg/day with slow tappering, allowed patient recovery within 1 week, without recurrence of pleural effusion. Six months later, the patient had no particular complains, and clinical examination was strictly normal, C reactive protein was < 5 mg/L and ANA titer was 320. During the following year, she experienced no recurrence.


A 36 years old woman with a suspicious diagnosis of cervical carcinoma in a tertiary hospital several days before visited our hospital. The patient had a regular menstrual cycle. Her childbearing history was G4P1A3, and she gave the birth by cesarean section in 2005. She was diagnosed with hypertension for five years and took medicine regularly, with blood pressure being controlled in normal condition.
She complained about vaginal bleeding after copulation for Six months, accompanying with constipation, diameter-thinning stool and an increase of vaginal discharge. She also complained that she had a mild pain sometimes in the low back and pelvis, without obvious association with menstrual cycle. So she came to a tertiary hospital specialized in gynaecology and did some examination according to the doctor’s advice. Pelvic ultrasound showed a 6.0 × 4.3 cm hysteromyoma and a 4.7 × 3.9 cm posterior cervical mass, with the ovaries found no abnormality. Enhanced pelvic computed tomography (CT) showed a 3.5 × 3.9 cm vaginal occupying lesion invading the rectum () and a 5.8 × 4.7 × 5.3 cm hysteromyoma. The doctor gave a suspicious diagnosis of cervical carcinoma.
Then the patient came to our hospital for further diagnosis and treatment. Additional examination was done. Examination of tumor markers showed that the serum level of CA125 was 87.9U/ml, 2.5 times of the normal upper limit, with squamous cell carcinoma antigen (SCC), CEA and CA199 within the range of normal value. Physical exam found that cervix uterus was thickened, with irregular shape and locally Protruding nodules. Vaginal and cervical biopsy only showed chronic inflammation. Colonoscopy examination found a mass at the rectum 4 cm from the anus () and biopsy indicated spindle-cell-like mesenchyma-derived tumor, with the immunohistochemical result not supporting the diagnosis of interstitialoma. Supplementary PET-CT examination showed an increase of 18FDG uptake of the rectal mass (), with the standardized uptake value(SUV) as 4.7. PET-CT reported that it was a submucous tumor, with interstitialoma being suspicious. Then another biopsy examination of the rectum mass was done and the diagnosis result was rectal endometriosis supported by the immunohistochemical result.
Multidisciplinary team, including oncologists, surgical specialists, gynecologists and pathologists, was established to discuss the complex condition. The pathologist supported the diagnosis of rectal endometriosis according to the immunohistochemical result. All doctors shared a common thought that there is a possibility that both rectal carcinoma and rectal endometriosis were existent at the same time, taking the small insufficient biopsy specimen into account. If a radical operation was performed, treating it as a malignant tumor, considering that the rectal mass was only 4 cm away from the anal verge, the patient could not save the anal function, and colostomy would be existent permanently, reducing the quality of life. After a heated discussion, a consensus that partial resection should be operated to confirm the histopathological diagnosis and then to determine the further treatment was achieved. Eventually, the final diagnosis was confirmed as rectal endometriosis and gynecological management was suggested.
Thereafter, the patient was discharged, seeking medical treatment in a tertiary hospital specializing in Gynecology. Gonadotrophin-releasing hormone antagonists was injected subcutaneously once per month for six months, with all the symptoms gradually disappeared. Then, a ring that slowly releases levonorgestrel was put into the uterine cavity, and it should be used until menopause according to the instruction.


A 66-year-old woman presented with polyuria and polydipsia for 3 weeks prior to evaluation by her primary care physician. Because of the concern for diabetes insipidus, the patient underwent MRI of the brain with and without contrast. Scans showed a right temporoparietal brain lesion ~4.5 cm × 4 cm in size (Fig. ). The patient underwent surgical resection, and the neurosurgeons achieved gross total resection with an absence of visible disease on contrast-enhanced MRI. A diagnosis of GBM was made and testing determined the tumor to be methyl guanine methyl transferase (MGMT) hypermethylated, EGFR amplified and EGFRviii positive.
The patient opted to enroll in a clinical trial that uses 3D spectroscopic MRI [] to monitor the metabolic response of patients to an experimental histone deacetylase inhibitor (HDACi), belinostat, concurrent with TMZ and radiation therapy. Pan-isoform HDACi’s like belinostat are hypothesized to have a synergistic effect with TMZ for radiosensitization of tumor cells; belinostat has more blood–brain barrier penetration than other HDACi’s []. A post-resection sMRI scan suggested the presence of residual non-enhancing disease. She received 60 Gy radiation in 30 fractions over 6 weeks in conjunction with belinostat and TMZ, and appeared to have stable disease per MRI 1-month post-radiation (Fig. ).
One month later, the patient experienced linguofacial swelling and hives after her first cycle of adjuvant TMZ. Recognizing this to be an allergic reaction, an extensive desensitization regimen was performed to no avail. The patient was taken off the clinical study and alternative chemotherapeutic agents were considered. Since the patient could not tolerate TMZ and refused to try other alkylating agents, and noting that her tumor exhibited mutated EGFR, she was started on erlotinib, an EGFR inhibitor used primarily in treatment of non-small cell lung cancer []. Concurrently, she began use of Novocure’s Optune, a device which generates low intensity TTFs via a scalp-mounted transducer array []. The patient has tolerated the treatment well and her complaints thus far have been left arm paresthesia while playing stringed instruments, as well as scalp, face and arm irritation from the Optune device. She is on a regimen of 7× 150 mg tablets of oral erlotinib weekly. Per imaging and clinical course, she appears to have stable disease 9 months post-radiation (Fig. ).


A 71-year-old man, originating from Vietnam, was referred to a tertiary care endocrine surgery center with incidentally found severe hypercalcemia of 3.65 (reference range, 2.20–2.62) mmol/L during routine follow-up for atrial fibrillation. His only symptoms of hypercalcemia on further questioning were fatigue and polyuria. The patient's history included the left leg dystrophy due to childhood polio, hypertension, atrial fibrillation, chronic kidney failure (stage IIIB), and dyslipidemia. He had no family history of parathyroid or other endocrine disease, and he had no prior neck irradiation.
On physical examination, a palpable mass was noted on the right lower neck without associated palpable lymphadenopathy. Flexible nasolaryngoscopy showed normal vocal cord movement, suggesting no invasion into the recurrent laryngeal nerve. Laboratory results showed markedly elevated levels of calcium at 3.3 mmol/L, PTH at 271 (1.4–7.6) pmol/L, alkaline phosphatase (ALP) at 446 (40–150) U/L, and phosphate of 1.06 (0.8–1.4) mmol/L. Ultrasound of the neck showed a complex, predominantly cystic nodule with solid components inferior of the right thyroid lobe measuring 4.1 × 3.6 × 3.1 cm ().
Sestamibi scan ((99m)Tc) displayed a dominant right-sided neck lesion with minimal uptake of technetium. Additionally, two well-defined lucent bone lesions, located in the right clavicle and scapula, showed increased tracer uptake (). Subsequent CT scans of the neck, thorax, and abdomen and a bone scintigraphy confirmed the presence of two previously defined osseous lesions along with two additional lucent and sclerotic lesions in the sternum and 7th rib. Differential diagnosis of the bone lesions included both metastasis as well as brown tumors secondary to long-standing hypercalcemia related to hyperparathyroidism. We did not evaluate the lesion with FNA preoperatively.
Due to the clinical suspicion of parathyroid cancer, en bloc parathyroidectomy with the right thyroid lobectomy and ipsilateral level VI lymphadenectomy was planned. Rivaroxaban, a direct Xa inhibiting anticoagulant indicated for atrial fibrillation, was stopped 5 days prior to surgery. The evening before the scheduled surgery, the patient presented to the emergency department with symptomatic hypocalcemia including perioral, finger, and toe numbness. Laboratory results showed profound hypocalcemia with a corrected calcium level of 1.85 (2.32–2.62) mmol/L, phosphate of 0.61 (0.8–1.4) mmol/L, and a decrease in PTH level to 87.5 (1.4–7.6) pmol/L ().
Repeated ultrasound showed further avascular solid components of this parathyroid mass but no changes in size of the lesion. Parathyroid tumor autoinfarction was suspected with concomitant hungry bone syndrome. The surgery was postponed, and the patient was treated with high-dose calcium supplementation and activated vitamin D. After eucalcemia was achieved, the originally planned surgical intervention was performed.
Rapid intraoperative PTH assays showed a significant drop of PTH after the removal of this mass (baseline intraoperative PTH, 134 pmol/L; 10-minute sample, 13.8 pmol/L). During the surgery, we used intraoperative nerve monitoring (IONM) for assessment of the right recurrent laryngeal nerve. The nerve signal was not lost throughout the operative dissection, and there were no adhesions to the recurrent laryngeal nerve from the parathyroid lesion. Postoperative movement of vocal cords was normal, calcium levels remained stable, and the patient was discharged 1 day after surgery.
The right hemithyroidectomy specimen identified a 4.0 cm mass located at the right perithyroidal region. The mass was an infarcted enlarged cellular parathyroid gland with cystic degeneration (). There was no evidence of angioinvasion or malignant invasive growth to suggest the morphological diagnosis of parathyroid carcinoma. Given the clinical suspicion for malignancy and underlying infarction, this lesion was further assessed with immunohistochemical biomarkers () [–]. The lesion was positive for PTH (confirming the parathyroid origin) and was negative for galectin-3 and PGP9.5. There was no loss of expression for parafibromin, Rb, p27, and bcl-2. The MIB-1 labeling index was 1%. The mitotic activity was 0.6 per 10 high-power fields (based on 3 per 50 high-power fields). The immunoprofile also did not suggest malignancy. While no atrophic rim of parathyroid tissue was identified, submitted additional parathyroid tissue from the right neck and significant drop of intraoperative PTH were suggestive of a single gland disease, consistent with an infarcted parathyroid adenoma [].
At the 6-month follow-up, calcium and PTH levels remained improved and no persistence or recurrence of disease was suspected.


A male patient aged 5-year-and-1-month was referred for genetic evaluation of development and speech delay, intellectual disabilities at the genetic counselling clinic in Shenzhen Maternal and Child Healthcare Hospital. The parents described that an affected brother also presented the same clinical phenotype but was not available for the clinical examination. The chromosome karyotype and chromosomal microarray analysis (CMA) in the proband were normal. The mother was pregnant again and pursued genetic counseling. The proband was subject to comprehensive neurological testing including the Gesell Developmental index. Molecular genetic tests and biochemical and neurochemical analysis were performed on the proband. The present study was approved by the hospital’s Institutional Review Board and written informed consent was obtained from their parents.
The proband was the second boy of healthy nonconsanguineous parents (pedigree in Fig. ). He was born at 39 weeks of gestation from an uneventful pregnancy and delivered by Caesarean section (weight, 3600 g; length, 50 cm; head circumference, 36 cm). He showed head control at 12 months, ability to sit by himself at 15 months, and walking with aid at 20 months. His verbal language was nearly absent and he made no visual contact. He suffered from seizures from 6 months old. He had no craniofacial dysmorphism. Gastrointestinal problems such as chronic constipation or nausea were noted in the proband. The physical examination on the proband showed 95 cm height, weight 18.2 kg and developmental and language delay. The proband also had an electroencephalogram (EEG) test, which showed sharp and slow waves in sleep during 24-h EEG monitoring. A brain stem auditory-evoked potential (BAEP) test showed mild abnormality. The proband had a Children’s Autism Rating Scale (CARS) score of 33, which indicated mildly autistic characteristics. The Gesell developmental scale test was used to evaluate the proband. Both the development age (DA) and developmental quotient (DQ) data showed extremely low grades which suggested severe development delay (adaptability, DA = 14.23mo., DQ = 23; gross motor, DA = 26.37mo., DQ = 43; fine movement DA = 15.87mo., DQ = 26; vocabulary DA = 13.07mo., DQ = 21; personal-social skill DA = 13.3mo., DQ = 22). The test results are depicted in Additional file : Figure S1A. The affected brother of the proband (II:1) was not available for the physical examination. The parental description of the clinical phenotype of the brother was mostly the same as the proband. The parents were physically healthy and indicated no significant past medical, surgical or family history.
DNA samples were provided from the index patient and other family members, which were extracted as previously described []. The present study used the TruSight One Sequencing Panel and NextSeq 500/550 Mid Output v2 kit (300 cycles) with high depth of coverage for 4813 target genes (approximately 62000 target exons) that are associated with clinically relevant phenotypes. An average sequencing depth of 136.88x was achieved and 98.25% of targeted variants were covered at least to a 10x depth, and 97.04% of targeted variants were covered at least by 20x. The total detected variants numbered 24594, which included 21,733 SNPs, 1,182 insertions and 1,679 deletions respectively. The data were analyzed on the TGex (Translational Genomics Expert) platform featuring with the VarElect scoring system []. A missense mutation, c.1181C > A (p.Thr394Lys), in the SLC6A8 gene was called with high probability as a candidate mutation.
Sanger sequencing was performed to confirm the SLC6A8 gene c.1181C > A mutation (forward primer 5’ ACGGAACTTGTCAGATTGT3’, and reverse primer 5’CAACAGCATGAAGAAGAACA3’). The father (I:1) was wildtype and the mother (I:2) was heterozygous for the c.1181C > A variation. The affected brother (II:1) and the proband (II:2) both carried the hemizygous variation of c.1181C > A. The pregnant mother had an amniocentesis at 22 weeks and Sanger sequencing targeting the SLC6A8 gene c.1181C > A was performed. The result showed a wild-type allele (II:3) and the mother gave birth to a healthy baby girl (Fig. ). In silico variant prediction analysis methods, including SIFT, PolyPhen2, PROVEAN, and Mutation Taster demonstrated this variant had probably damaging or diseasing-causing effects.
Biochemical screening was performed with blood and urine samples from the proband and his mother. The creatine/creatinine (Cr:Crn) ratio was determined by liquid chromatography-mass spectrometry with deuterated internal standards in two urine samples taken on different days. A urine creatine test of the proband showed significantly elevated levels of creatine (0.805 mg/ml, normal control 0.160 ± 0.177 mg/ml) (Additional file : Figure S1B), and the creatine/creatinine ratio was significantly elevated compared to controls. Proton magnetic resonance spectroscopy (MRS, Magnetom Skyra 3.0-T, Siemens Healthcare GmbH, Erlangen, Germany), examination using a 3.0-T system at the brain left parietal lobe, right parietal lobe and genu of corpus callosum all showed marked reduction of the brain creatine peak (Fig. left part). Brain MRI showed a thin corpus callosum in the proband (Fig. right part). The MRS and MRI examination of the mother (I:2) showed normal results (Additional file : Figure S1C).


On January 4th, 2018, a 57-year-old woman was hospitalized in the department of Psychiatry, Sir Run Run Shaw Hospital because of pain and acid bilge in multiple sites of her upper body for more than 1 year. Over a year ago, the patient started feeling pain and discomfort in the upper left abdomen, and the pain got worse when coughing but with no other discomfort. Two months later, the upper left abdomen pain and acid bilge extended to the front chest, back, abdomen, and upper limbs. The symptoms persisted for months, and aggravated when changing body posture. Test results including cervical MRI, chest CT, abdominal B ultrasound of upper abdomen in a local hospital showed no abnormalities. Treated with Chinese medicine for more than 3 months, there was no significant improvement. About 6 months ago, the patient came to our hospital, expressing the symptoms above and worries about them, with weight loss of about 1–1.5 kg, but denying continuous depression, anxiety, and other symptoms (the score of 24 items of Hamilton Rating Scale for Depression was 12, and Hamilton Anxiety Rating Scale score was 11), and was diagnosed as “somatic symptom disorder.” After 4 months of treatment with 60 mg of duloxetine enteric-coated capsules twice daily and hypnotic drugs, the symptoms were obviously alleviated but not completely relieved and there was a significant weight loss of about 5 kg. Therefore, medication was adjusted to escitalopram tablets 20 mg once daily. Two months later, the patient felt no further improvement.
With hypertension history of more than 10 years, the patient claimed that it's not necessary for her to take any antihypertensive drugs to control blood pressure in recent 1 year. She had bronchitis for 12 years but no medicine was needed. She denied any history of diabetes, heart disease and other diseases and claimed there was no history of surgery and trauma. Also, the patient denied long-term chemical substances, drug or poison exposure history and had no history of smoking and drinking alcohol.
After admission, due to long-term poor efficacy of the patient, we re-evaluated the patient's physical condition to rule out organic diseases. However, through Blood routine, Blood Biochemistry, Stool Routine, Urine Routine, Chest Film, Electrocardiogram, and so on, no specific abnormality was found. We found that the patient's tumor marker CA-153 was 61.2 U/mL (< 25.00 U/mL) and ferritin was 198.70 ug/L (13.00–150.00 ug/L), with no specificity. There was another finding of patient suffering from cholecystitis and gallstones through abdominal ultrasound examination; however, the surgeon suggested that it could not explain the patient's symptoms. When perfecting cranial MRI, we unexpectedly discovered below result: diffuse thickening of the skull and increasing signal intensity. Metastasis? Multiple myeloma? (Figure ).
And lumbar MRI prompted lumbar vertebra, attachment and right iliac bone multiple bone changes, multiple myeloma? Transfer? (Figure ). Skull and pelvis plain radiographs prompted skull, maxillofacial bone, pelvis, and femoral bone changes, multiple myeloma? Transfer? (Figure ).
After perfecting corresponding blood examination, the patient eventually underwent bone marrow aspiration and the results suggested that the patient was suffered from multiple myeloma (Figure ). The patient was finally referred to the hematology department and received appropriate treatment.
Here we report on a case of a 57-year-old woman with pain and discomfort in multiple sites of upper body who was diagnosed as somatic symptom disorder after completing a partial examinations of relevant parts which turned out to be negative. Finished imageological examinations of all painful parts, she was eventually diagnosed with multiple myeloma after 6-month being misdiagnosed as somatic symptom disorder. This case highlights the importance of completing imageological examinations of all the painful parts of the patient to exclude the possibility of multiple myeloma especially when symptoms are associated with objective signs and treatment has been ineffective; and it is as well as significant to notice characteristics of symptoms and to pay excessive attention directed toward the symptoms in the diagnosis of somatic symptom disorder.
MM is a disease which is characterized by the neoplastic proliferation of immunoglobulin-producing plasma cells. Most patients with MM present with signs or symptoms related to the infiltration of plasma cells into the bone or other organs or to kidney damage from excess light chains. MM accounts for ~1–2% of all cancers and slightly more than 17% of hematologic malignancies (). Worldwide, there are ~154,000 cases and 101,000 deaths per year attributed to MM (). MM is also slightly more frequent in men than in women (~1.4:1). The risk of developing MM increases with body mass index (, ). MM is a disease of older adults. The median age at diagnosis is 66 years; only 10 and 2% of patients are younger than 50 and 40 years, respectively (, ).
Most patients with MM present with signs or symptoms related to the infiltration of plasma cells into the bone or other organs or to kidney damage from excess light chains. As an example, a retrospective analysis of 1,027 sequential patients diagnosed with MM at a single institution found the following symptoms and signs at presentation: Anemia-73%, Bone pain-58%, Elevated creatinine-48%, Fatigue/generalized weakness-32%, Hypercalcemia-28%, Weight loss-24%, one-half of whom had lost ≥9 kg ().
In American Psychiatric Association's Diagnostic and Statistical Manual, Fifth Edition (DSM-5) (), SSD is characterized by one or more somatic symptoms that are accompanied by excessive thoughts, feelings, and/or behaviors related to the somatic symptoms. It is estimated the prevalence in the general population is 4% (, ) and that among primary care patients is 17% (, ). An analysis of individual patient data from nine community studies (total n > 28,000) found that the most frequent burdensome symptom was pain (). SSD is not defined by the number of distressful physical symptoms that are present; however, patients who complain about multiple symptoms are more likely to have the disorder. In this case, the patient had a number of pains and acid bilge in multiple locations which are typically present in somatic symptom disorder, with no other symptoms of MM, for instance, anemia, elevated creatinine, fatigue/generalized weakness, hypercalcemia. These enhance the possibilities of misdiagnosing MM as SSD. The percentage of underlying somatic diseases in patients previously diagnosed with SSD is relatively small but unneglectable. A meta-analysis () reviewed six diagnostic evaluation studies (total N = 1,804 patients), 16 follow-up studies (total N = 2,440 patients), and the percentage of misdiagnosis with SSD was 8.8% (95% CI 1.0–22.2, p = 0.007) in diagnostic evaluation studies, 0.5% (95% CI 0.01–1.5, p = 0.03) in follow-up studies, while the correct diagnosis shall be diabetes mellitus, duodenal ulcer, Crohn's disease, polymyalgia rheumatica, carcinoma, herniated disc, and so on.
Imaging is a key part of the evaluation of all patients with suspected MM. In this case, we found some related negative imaging test results like cervical MRI, chest CT, abdominal B ultrasound of upper abdomen from another hospital, however, neglected to do examinations of other important parts where the patient reported discomfort, such a lumbar and pelvis imageological examinations. Pain and acid bilge in multiple sites are usually associated with musculoskeletal and nervous system disease, and MRI is the best imaging choice for the early stage of these diseases. In the diagnosis procedure of SSD, thorough physical examination, laboratory tests and imageological examinations are necessary to help clinicians and patients build confidence and ensure that no important diagnosis will be missed (–). Moreover, criteria for selective use of tests include objective signs rather than the volume of the concerns expressed by the patient, the presence of complex symptoms, and persistence of symptoms (). For instance, in our case, the pain of the patient aggravates when the body posture is changed or coughing. This characteristic probably points to a physical disease which is ignored during the early processes of out-patient treatment.
SSD patients always have excessive thoughts, feelings, or behaviors associated with the somatic symptoms. The patient was also anxious because of her symptoms which now we can consider it as healthy anxiety. Clinicians taking a history should determine whether somatic symptoms trigger healthy anxiety or not, in addition, determine whether the patient manifests persistent thoughts and anxiety related to the somatic symptoms, and whether the patient devotes excessive time and energy to the somatic symptoms (–). In International Classification of Disease-10 (ICD-10) () which is currently widely used in the world, somatoform disorders are defined on the basis of failure to find physical causes rather than the presence of definite psychological and behavioral features. The notion of taking medically unexplained symptoms as the defining feature of ICD-10 somatoform disorders creates a major hindrance to the clinical utility of the diagnosis. There is evidence that the decision about whether symptoms are medically unexplained is unreliable and lacks validity. The inherent dualism in the notion of a lack of medical explanation for somatic symptoms that are cross-sectionally assessed is simplistic and ultimately unhelpful to patent care (). In ICD-11 (), excessive attention directed toward the symptoms is highlighted in the diagnosis of Bodily distress disorder.
There is evidence that antidepressants are effective for SSD (, ). However, SNRIs could relieve pain by inhibiting reuptake of serotonin and norepinephrine, and suppressing painful sensation uploading regardless of physical disease or psychiatric disorders. Therefore, pain of the patient was obviously alleviated after 4 months of treatment with 60 mg of duloxetine enteric-coated capsules twice daily. This phenomenon also could perplex the revision of the diagnosis.
This case indicates that imageological examinations of all the painful parts of the patient should be completed to exclude the possibility of MM, especially of those whose symptoms are associated with objective signs and treatment has been ineffective. Furthermore, diagnosis of SSD requires not only the elimination of somatic diseases, but also excessive thoughts, feelings, or behaviors associated with the somatic symptoms.


A 60-year-old woman underwent transurethral resection of bladder tumor (TURBT) at our institute in 2004; her pathological diagnosis was a high-grade UC with adenocarcinomatous differentiation (pT2a, G2>G3). Radical cystectomy was conducted. Only carcinoma in situ (CIS) was found in the surgical specimen, and the surgical margin was negative. There was no cancer cell infiltration in the resected uterus or anterior wall of the vagina, and no lymph node involvement was detected. The patient developed continuous pain and bleeding from the residual vagina in 2010, and a tumor was found in the residual vagina; magnetic resonance imaging (MRI) showed it to be located on the anterior wall (). A biopsy of the tumor revealed a pathological diagnosis of adenocarcinoma (). Computed tomography (CT) and bone scintigraphy revealed no metastasis. Based on a preoperative diagnosis of a primary adenocarcinoma occurring on the residual vagina, tumor resection was performed (). The sigmoid colon was partially resected as it was strongly adherent to the tumor. On pathological examination, adenocarcinoma and SCC were detected (); on immunohistochemistry, sections of the tumor were positive for the SCC markers CD56, chromogranin A, and synaptophysin and were negative for the urothelial carcinoma markers GATA-3, p63, uroplakin, thrombomodulin, and 34βE12. We then reexamined the original TURBT specimen and confirmed the presence of SCC (). Adenocarcinoma and SCC were mostly present in the superficial layer of the TURBT specimen, while high-grade UC was found in the deeper layers where muscle invasion was present. Based on these findings, the tumor was diagnosed as a recurring bladder tumor. Local recurrence and pelvic bone metastasis were detected via MRI 3 months after the patient underwent surgical resection of the vaginal recurrence, whereupon she underwent radiation therapy (52 Gy, 26 fractions). She developed ileus in January 2011 and underwent release surgery. Subsequently, multiple lung metastases and local recurrence in the pelvis developed in June, and she died of disease progression the following month.


A 46-year-old female patient underwent a left hip resurfacing arthroplasty (Birmingham®, UK) for severe hip osteoarthritis, secondary to developmental hip dysplasia, in 2005. She had a good initial outcome with no complications. The surgery was performed in another centre.
She consulted with us for the first time six years later (2011) complaining about hip pain and paresthesia in the anterior left thigh, which progressively compromised her function. She denied fever or other signs of infection. Physical exams revealed a mild claudication gait and limited active and passive hip flexion. No palpable masses or skin lesions were observed. Laboratory analyses showed a WBC, ESR, and CRP within normal limits. No signs of osteolysis were found in the hip anteroposterior radiography; nevertheless, a vertical cup was noted (). It was compared with the immediate postsurgery radiography, and no change was noted.
Computed tomography and an MRI demonstrated a biloculate hypodense mass of approximately 34 × 19 cm that extended from the retroperitoneum, compromising the left iliopsoas muscle and an intimate contact with the femoral vessels, to the left hip and the left femoral-cutaneous nerve (Figures and ). A routine hip arthrocentesis was performed to rule out infection. The cytochemical and Gram analyses were negative for infection. Cultures were negative after 14 days.
Thus, a pseudotumour was the diagnosis, and surgery led by an orthopaedic surgeon and a coloproctology surgeon was planned. The aim was to remove the pseudotumor entirely and to perform an RHA. As the CT shows (), the intrapelvic mass was significant, so it was decided to start with a laparotomy by the coloproctology surgeon.
First, the patient was positioned supine, and an infraumbilical laparotomy was performed; the left paracolic gutter was dissected to address the retroperitoneum. The iliac vessels and the left ureter were protected, and an irregular cystic mass was observed in direct contact with the psoas muscle and femoral bundle. It was punctured, and an abundant grey milky-like fluid was obtained. The membrane of the cyst was carefully removed, protecting the vessels and the femoral nerve. The lesion was completely resected, and samples were sent for biopsy and cultures ().
Then, the patient was repositioned in lateral decubitus, and a posterolateral hip approach was performed. The capsule was looking distend; it was punctured and then, a 30 cc fluid was obtained, similar to the liquid found in the retroperitoneum. After capsulotomy and femoral neck osteotomy, all arthroplasty components were removed, noticing an anterosuperior wall defect in the acetabulum. After complete pseudotumour resection, RHA was performed (). The acetabular cup component was a cementless 56 mm Dynasty® (Wright Medical, Memphis, USA), and the femoral component was a high offset femoral cementless stem (Stellaris®, Mathys, Bettlach, Switzerland, no. 17). The bearing surface used was polyethylene-ceramic, being Dynasty® polyethylene liner, on the acetabulum and a 40 mm ceramic on the femoral head (BIOLOX®, Mathys, Bettlach, Switzerland). Post surgery, an anteroposterior pelvic radiograph was taken (). After fourteen days, tissue cultures obtained at surgery were negative for infection.
Histopathological findings confirm the pseudotumour. The analyses reported an extensive aseptic inflammatory infiltrate of macrophages with detritus inside near a necrotic tissue area (). A PAS histochemical stain confirmed these findings. No signs of ALVAL were observed. Also, reparative tissue was found with black particulate material corresponding to the prosthetic material near the neoformation of blood vessels and fibroblast ().
No early- or late-surgery complication is reported. Since post surgery, the patient progressively recovers the hip's range of motion and normal gait. In the last follow-up, 60 months postoperatively, the patient is in excellent condition with no functional limitations and a full hip range of motion. Radiological exams, which included an annual MRI, showed no pseudotumour formation and no arthroplasty loosening. The MRI at five years of follow-up is shown in .


A 59-year-old male patient presented with widespread edema and decreased urine output. The patient had no history of active arthritis, hemoptysis, bleeding, purpura, fever, chills, weight loss, streptococcal infection or known tropical disease and had not suffered from asthma or any other atopic diseases. At the time of his visit to our hospital, his blood pressure was 136/93 mmHg, and his temperature was 36.9 °C. The physical examination showed that the patient was suffering from left-sided hearing loss and revealed the presence of a palpable swollen mobile and non-tender lymph node with a size of approximately 1.5*1 cm located behind the left ear. No other superficial lymph nodes were palpable. A urinalysis showed 3+ proteinuria and 3.68 g of proteinuria in 24 h.The serum albumin (Alb) concentration was 11.3 g/L, the serum creatinine concentration was 218.7 μmol/L, the BUN concentration was 25.33 mmol/L, the eGFR was 27.4 mL/min/m2, and the ESR was 112 mm/h. The patient’s serum complement (C3 and C4) levels, antinuclear antibody titers, antistreptolysin O titers, and hepatitis screening results were normal. Hematology revealed a normal hemoglobin concentration and platelet count, a total white blood cell count of 6.98*10E9/L, and a percentage of eosinophils of 6.6%. The serum IgE concentration was elevated, as it was higher than 4000 IU/mL. A Mycobacterium tuberculosis γ-interferon release test was negative, and a bone marrow biopsy did not display obvious abnormalities. A neck CT showed that the cervical vascular sheath was surrounded by several small lymph nodes, and an ultrasound demonstrated the presence of bilateral pleural effusions and ascites. Pleural effusion examination revealed a karyocyte count of 76*10E6/L, a neutrophil count of 12%, a lymphocyte percentage of 85%, an Alb concentration of 1.8 g/L, a lactate dehydrogenase (LDH) concentration of 44 U/L, and an adenosine deaminase (ADA) concentration of 1.3 U/L.
Histological sections of lymph nodes were examined in the department of pathology. The examinations revealed the presence of follicular and interfollicular hyperplasia and the proliferation of venules surrounded by infiltrating eosinophils, lymphocytes, plasma cells, and mast cells. An eosinophilic microabscess was detected in the cortical area of the lymph nodes (Fig. ). These findings confirmed the diagnosis of KD.
Renal biopsy showed that two glomeruli were sclerotic (13 glomeruli were assessed). The remaining glomerular mesangial cells and stromal cells showed signs of mild proliferation. No significant widening of the mesangial area was observed, and the basement membrane had no obvious lesions. The tubular epithelial cells displayed signs of vacuolization. Additionally, part of the renal tubular epithelium had flattened, and the bristles had fallen off. Small numbers of protein casts were present in the dilated tubules. No obvious interstitial inflammatory cell infiltration (including eosinophil infiltration) was present, and no IgG, IgA, IgM, C3, C1q, C4 or Fib deposition was noted in any of the glomeruli. Electron microscopy showed mild hyperplasia of mesangial cells and stromal cells, extensive fusing of the podocyte processes of the epithelial cells, and a lack of electron-dense deposits (Fig. ).These findings confirmed the diagnosis of MCD combined with acute renal tubular injury.
The patient’s volume load did not respond to diuretics, and his urine output decreased. Furthermore, increases in the patient’s urea and creatinine levels were observed. Therefore, hemodialysis was initiated to improve the patient’s edema and kidney function. The renal biopsy demonstrated the presence of MCD combined with acute renal tubular injury. The patient was ultimately diagnosed with KD associated with MCD and acute renal tubular injury. The patient subsequently received 40 mg/day methylprednisolone for 3 weeks. Urinary protein and renal function were monitored during treatment, which decreased the patient’s serum creatinine level to 62.3 μmol/L, increased the eGFR to 103 mL/min/m2, increased the serum albumin concentration to 15.6 g/L and significantly increased urine output compared with pre-treatment values. However, the patient’s proteinuria increased to7.02 g/day.
The patient withdrew from hemodialysis and continued taking 40 mg/day prednisolone after discharge, but returned to our hospital after 6 weeks. At that time, urinalysis revealed 1+ proteinuria. The serum albumin concentration was 37.5 g/L, the serum creatinine concentration was 69.4 μmol/L, the BUN concentration was 12.55 mmol/L, and the eGFR was 97.8 mL/min/m2. The changes in the patient’s laboratory indexes are shown in Fig. .
Several databases, including PubMed, EMBASE, MEDLINE (Ovid), the Chinese National Knowledge Infrastructure (CNKI), the VIP Database for Chinese Technical Periodicals (VIP), and WanFang Data, were systematically searched from the date of database inception until Nov 01, 2017 to collect published international and domestic studies with the term “Kimura’s disease” and “Nephrotic syndrome”. The selection criteria were as follows: 1). studies including patients who were diagnosed with KD by lymph node or mass biopsy; 2). studies in which renal involvement was noted in all patients, and renal biopsy was used to define the pathology. The exclusion criteria were as follows: 1). studies which the patients were diagnosed with Kimura’s disease but with no renal involvement; 2). the data provided by the articles could not be accessed, or the full text could not be transformed. 3). the articles were reviews or abstracts. Ultimately, 18 studies [, , –] were included in the analysis. 8 studies [, , –, , , ] were published in English, and the others were published in Chinese. 26 patients were involved in this review. 20 patients were from China, 2 were from India, and one each was from Japan, Turkey, Vietnam, and Egypt (Table ).
Of the 26 patients included in the review, two were female and were from China and India, respectively, and the remaining patients were male. Thus, the male-to-female ratio was 12:1. Most of the patients presented with cervical lymphadenopathy or subcutaneous masses in the head or neck region. The mean age of these patients was 31.1 ± 14.2 years, the daily protein excretion level was 8.04 ± 4.62 g/24 h, the serum albumin concentration was 21.2 ± 8.57 g/L, the serum creatinine concentration was 170 ± 190 μmol/L, the blood eosinophil count was 23.7 ± 15.4%, and the IgE titer was 1285 ± 1223 IU/mL.
Renal biopsy was performed in all patients. Most of the patients presented with mesangial proliferative glomerulonephritis (13 patients). Other patients presented with membranous nephropathy (4 patients), minimal change disease (3 patients), focal segmental glomerulosclerosis (3 patients), IgA nephropathy (2 patients) and acute tubular injury (1 patient).
The majority of patients were treated with corticosteroids alone, while a small number of patients received corticosteroids combined with immunosuppressive agents, such as Tripterygium wilfordii, cyclophosphamide and leflunomide. With the exception of 2 patients who progressed to ESRD (end stage renal disease) and received hemodialysis, all other patients achieved remission with respect to their proteinuria. Simultaneously, the neck lymph nodes or masses became smaller. However, 5 patients experienced a proteinuria relapse during follow-up, including 4 patients with mesangial proliferative glomerulonephritis and one patient with membranous nephropathy.


A 71 year-old male presented for an urgent biopsy of a lesion of Corpus Callosum on a background of clinically diagnosed intra-operative anaphylaxis for the same procedure 4 days prior, which was abandoned. Symptoms of the initial presentation, which brought the patient under the care of the Neurosurgical team, included impaired ability to self-care and mild cognitive dysfunction. Surgical and Medical teams deemed the histo-pathological diagnosis essential due to the need for tailored subsequent medical management including potential urgent administration of chemotherapy and radiation.
The specialised allergy testing was not feasible due to the brief 4 day timeline proposed between the two procedures. Decision was made to proceed with surgery due to the urgent need for the identification of the nature of the lesion.
Both patient and the prior care episode were evaluated. Patient had a background of treated hypertension, with no other underlying illnesses. Prior to this, he had undergone uneventful surgical procedures and anaesthesia.
History, records of the procedure, and tests for mast cell mediators, were reviewed by the attending anaesthetist. During the first care episode patient was given a single dose of midazolam, followed by remifentanil and propofol total intravenous anaesthesia, rocuronium and cephazolin in quick succession. The laryngoscopic view was a Grade 3 Cormack and Lehane, with direct laryngoscopy utilising a Macintosh 4 Blade. CMAC® Blade 4 Videolaryngoscope demonstrated an equivalent Grade 3 Cormack and Lehane view. Following successful airway management, patient developed intractable hypotension, concomitant bronchospasm and was diagnosed with clinical anaphylactic episode. The patient was treated with an adrenaline infusion, procedure was abandoned and he was admitted with an endotracheal tube in situ to Intensive Care Unit where he recovered uneventfully. The patient re-presented 4 days later for a repeat procedure. Specific allergen testing was unavailable and deemed not to be feasible at this point in time.
During the repeat care episode, decision was made to secure the airway via an awake flexible endoscopic intubation prior to administering general anaesthesia. Airway was topicalised generously using a mix of 4% nebulised xylocaine, 10% local anaesthetic sprays to the back of the pharynx, and topical co-phenylcaine nasal spray. In addition to the above, Disposable devilbis atomiser was used to a total of 9 mg.kg− 1 of xylocaine. Remifentanil infusion at the dose of 0.05 mcg.kg− 1.min− 1 was used during the intubation and airway was secured uneventfully through the nose with a flexible Storztm 5.1 mm video fiber-optic bronchoscope. After connecting the breathing circuit, confirmation of CO2 was obtained and patient was administered 250 mg of thiopentone. Remifentanil infusion was increased to 0.2 mcg.kg− 1.min− 1 and maintained at this level through the case. Anaesthesia was maintained with Sevoflurane at a total dose of less than 1 MAC. For infection prophylaxis, 600 mg of clindamycin was administered. Procedure was completed uneventfully, patient extubated and taken to recovery. Using the above technique, the only medication in common between the two episodes of care was remifentanil.