A 77-year-old lady with no known medical illness was admitted to our hospital with recurrent episodes of falls within two days duration. She described the falls without any mechanical component, associated with dizziness and sustained causing several bruises over her face, right forearm, and bilateral legs. She also reported of unsteady gait which caused her to veer towards her right side. She denied any postural dizziness, weakness in the limbs, visual or speech disorder. She also had reduced exercise tolerance after multiple falls but denied any chest pain or palpitation.
On examination, she was oriented to time, place, and she had blood pressure of 135/70 mmHg and the heart rate of 78 bpm. Her cardiovascular examination was unremarkable with no audible murmur or carotid bruit. Neurological examination revealed a reduced power for all limbs with the strength of 4 out of 5. However, tones, reflexes, and sensations of extremity muscles were within normal limits. Examination of cranial nerves was unremarkable with negative cerebellar signs.
A baseline ECG () showed a sinus rhythm with concave ST segment elevation over leads I, II, V3 -V6 and reciprocal ST depression in lead III. Furthermore, PR elevation is observed in lead a VR. Hemoglobin value was 13.4 g/dL with total white cell, and platelet counts of 16.4x109/L and 276x109/L, respectively. Electrolytes were within normal ranges (urea, 6.4 mmol/L; creatinine, 70 mmol/L, and potassium 3.7 mmol/L). Troponin I was elevated (14.51 ng/mL).
Computerized Tomography (CT) of the brain was performed () and reported as fairly ill-defined hypodensity at the right corona radiata in keeping with subacute infarcts, and well-defined hypodensities at the left head of caudate nucleus extending to the anterior horn of the left internal capsule, the left basal ganglia, and the left external capsule in keeping with chronic infarcts.
Thus, a diagnosis of lacunar infarct was made in correlation with her symptoms and CT brain findings. However, an additional diagnosis of acute coronary syndrome (ACS) was assumed in view of ECG changes with elevated troponin I level. Therefore, she was commenced on dual antiplatelet treatment and referred to a cardiologist. Emergency Coronary angiogram was arranged which revealed the presence of normal coronary arteries. Ventriculogram was performed, classical apical ballooning was shown, suggestive of Takotsubo Cardiomyopathy (). Her recovery was uneventful, and she was discharged with daily doses of aspirin (100 mg), perindopril (2 mg), atorvastatin (40 mg), and bisoprolol (1.25 mg). She was subsequently seen in the outpatient clinic after a month with no neurological deficit. In addition, a transthoracic echocardiogram was performed on the same setting and noted ejection fraction (EF) of 65% without regional wall motion abnormality.


A 4-day-old full-term male newborn presented to pediatrics emergency with history of multiple seizures and poor intake since day 3 of life. Antenatal history was normal and the baby was born by normal vaginal delivery. There was no sepsis setting in mother and no history of birth asphyxia in the baby. Baby was second in order and the first sibling was normal on physical examination with no congenital anomalies. Baby was having refractory subtle as well as multifocal clonic seizures. The convulsions were refractory to anticonvulsant drugs such as phenobarbital, phenytoin, and levetiracetam.
On physical examination, the newborn had birth weight of 2.2 kg (small for gestational age), length of 51 cm (50th percentile), and occipitofrontal circumference of 32 cm (microcephaly).
The baby was dull looking and vital signs were normal. Anterior Fontanelle was at level, heart and lung sounds were normal and there was no organomegaly. The baby was hypotonic, lying in semi-flexed posture with poor cry and suck reflex. He had a micropenis (5 mm) with a single urethral opening and bilateral cryptorchidism []. There were no palpable gonads in bilateral inguinal region.
Sepsis screen was negative in the patient. Other biochemical investigations like serum electrolytes including ionized calcium, liver, as well as kidney function tests were normal. CSF examination was also normal. Patient had hypoglycemia intermittently but seizures persisted even blood sugar levels were normal. Intermittent episodes of hypothermia were present during the hospital stay. Levels of 17 OH progesterone (1.52 ng/ml), TSH (1.52 mIU/L), Cortisol (6.80 mcg/dl) were normal and testosterone was not detectable (0.00 ng/ml). Neither uterus nor testis were seen in USG abdomen. Normal male karyotype (46 XY) was seen on chromosomal analysis (46, XY).
MRI brain showed abnormal gyral pattern with smooth broad gyri suggestive of Lissencephaly pachygyria spectrum. There was corpus callosum agenesis with parallel orientation of lateral ventricles. A large interhemispheric cyst was seen in mid posterior interhemispheric region measuring 6.5 × 2.6 × 3.9 cm. Posterior fossa structures, bilateral thalami, and basal ganglia were normal [].
EEG showed abundant spike wave discharges suggestive of epileptic encephalopathy []. Genetic analysis could not be done due to financial crisis of parents, though the genetic nature of the disease and its recurrence in future pregnancies was appropriately explained.
Baby was managed on multiple antiepileptics still seizures remained uncontrolled. Baby finally expired on day 25 of life. Patient consent form was obtained from the parents and ethical clearance was taken from the institution.


A 26-year-old female with history of recent international travel presented with fever and excessive fatigue for 1 day. She also complained of sudden onset loss of taste and smell. On admission she was stable, with normal vital parameters, no tachypnoea and maintained 100% saturation on room air. The systemic examination was unremarkable. In view of her symptoms and history of recent international travel, a clinical diagnosis of COVID-19 was made. The oropharyngeal and nasopharyngeal swab specimens were sent for RT-PCR, which were positive. The swabs were also tested for Influenza A and H1N1 coinfection, but were negative. Complete blood counts and other investigations performed during hospitalization are summarized in . Chest X-ray was normal. She was initiated on oralamoxycillin-clavulanate and azithromycin for 5 days. Defervescence of fever was noted on Day 2 and she remained afebrile during her hospitalization. However, her anosmia and ageusia were persistent. Repeat test for COVID-19 on Day 7 (2 samples) and day 14 (2 samples) were negative. She was discharged subsequently after a period of hospital isolation of 14 days. However, there was little improvement in the symptoms of loss of taste and smell, which were still persistent.


A 40-year-old female patient reported to the dental OPD with chief complaint of pain in the lower right and left side of jaw since 2 months. Patient reported that she noticed multiple ulcerations in the attached and marginal gingiva on the right and left mandibular region since 14 months. Initially, ulcers healed by themselves, but with time the exacerbation of ulcers increased and presently the ulcerations did not heal for months. History of pain with the similar kind of ulcers was evident which was dull, aching, nonradiating in nature with no aggravating or relieving factors. Noted a history of bleeding while brushing. No history of any sensory loss, exfoliation of tooth, intraoral burn, or pus discharge from the affected areas. Medical history revealed that the patient was HIV positive and is under antiretroviral treatment (ART) for the last 10 years since 2009. Presently, the CD4 count for the patient was 250. History of fatty liver associated with splenomegaly since 2 years and was under treatment. Patient was married and her husband was also HIV positive patient since 2001 before marriage and was under HAART therapy. Patient had 2 sons who were not affected. No history of any smoking or smokeless tobacco. On general examination, patient was well oriented to time place and person. Temperature was afebrile, pulse 78/min, blood pressure 110/85 mmHg, and respiratory rate 15/min. Built was lean and gait was normal. On extraoral examination, no gross facial asymmetry present. Noted hyperpigmentation on the left malar region []. Swelling present on the lower right chin region, on inspection size 2 cm × 1 cm approximately, shape roughly oval, surface covered with crustrations, reddish in color, margins well defined. On palpation, the inspectory findings were confirmed. Consistency was soft, tenderness was present, and no bleeding or pus discharge on manipulation; similar swelling of smaller size was present 1 cm anterior to it []. Lips were competent and TMJ movements bilaterally were smooth and synchronous. A single right submandibular lymph node was palpable of size 1 cm × 0.5 cm approximately, shape roughly oval, firm in nature, fixed to the underlying structure, and tender on palpation. On intraoral examination, there were multiple ulcerations present with the lower anterior region and right side of jaw extending anteroposteriorly from 35 to 46 region. Consistency was soft to firm in nature; surface was covered with yellowish slough surrounded by erythematous halo. Ulcerations were seen both buccal [] and lingual side [] of the alveolus in the same region. Similar ulceration was seen in the maxillary jaw extending anteroposteriorly from 21 to 24 region on the lingual side, and erythema with a bluish hue with swelling was seen on the buccal side of maxillar []. Gingiva was normal with no bleeding on probing and no clinical pockets. With the clinical examination, the provisional diagnosis was KS affecting the maxillary and mandibular jaw.
Patient was advised to get the CD4 count and routine blood report. The report revealed CD4 count was 220 cells/mm3, hemoglobin was 10.2 g%, and total white blood cell count was 8400/mm3. The other blood investigations were within normal range.
Histological examination from the ulcerative area from the right side of gingiva revealed angiomatoid slit like vascular spaces containing red blood cells surrounded by spindle cells []. The spindle cells were arranged in fascicles and their nuclei did not show any atypical features or mitotic activity. In between tumor cells, deposition of hemosiderin pigment and infiltration by mononuclear cells were identified which were suggestive of KS.
The treatment advised was oral prophylaxis and antiretroviral therapy (lamivudine 150 mg BD, stavudine 30 mg BD and efavirenz 600 mg HS) with chemotherapy. There was no improvement in patient's condition and she died within 9 months


A 22-year-old female graduate engineer presented to the accident and emergency unit with recurrent episodes of bleeding per rectum for the past 2 years which was bright red, devoid of stools and associated abdominal pain. The index presentation at the accident and emergency unit was severe with about five (5) episodes associated with dizziness, palpitations, and easy fatigability. Significantly, she had lost weight and had not noticed any protrusion of mass from the anus on defecation or had any history of epigastric pain or haematemesis.
On examination, she had signs of blood pressure of 80/40 mmHg and a pulse of 120 beats per minute. Abdominal examination was unremarkable. On digital rectal examination, haemorrhoids were felt and the examining finger was however stained with bright red blood. She was resuscitated with crystalloids and blood products. Initial Hb on presentation was 4.3 g/dL.
Colonoscopy up to the sigmoid colon done showed external haemorrhoids, numerous polyps of varying sizes throughout the rectum and sigmoid colon from which biopsies were taken (). The rectal polyps were few (). Histology showing low-grade dysplastic epithelium comprised of hyperchromatic and elongated nuclei arranged in a pseudostratified manner (). Features consistent with tubular adenoma with low-grade intraepithelial neoplasia (). However, a carcino-embryonic antigen test done at the time was 12.4 μg/L.
A computed tomography (CT) virtual colonoscopy was done to complete the picture which detailed the extent of the polyps (). Thousands of polyps filling the entire colon with relative sparing of the caecal region and the proximal part of the ascending colon covering a length of ~15 cm (). With sizes ranging from millimetres to the largest measuring ~2.6 cm.
The patient was optimized for surgical intervention with more blood products followed by laparotomy with subtotal colectomy (with bowel length of 62 cm) and ileorectal anastomosis. Intra-op multiple polyps spanning the entire colon was seen. Histopathology report of the colonic specimen revealed mucosal surface with a myriad of multiple raised lesions (>1000). The smallest had an average size of 0.5 × 0.5 cm. In some areas, the lesion appeared in aggregate with areas of mucosal ulceration. Seven lymph nodes were retrieved from the attached mesentery. Microscopically, multiple adenomatous polyps with mild dysplasia were seen. There were no high-grade changes. The section from the appendix shows lymphoid hyperplasia with reactive follicles. There was no malignancy or severe dysplasia. However, features were consistent with Adenomatous Polyposis Coli.
Fourteen days post-op, the patient has shown marked improvement in recovery with Hb of 12.9 g/dL and carcino-embryonic antigen test was 2.1 μg/L. The patient was placed on a high-fibre diet and is currently doing well.


A 67-year-old man was diagnosed with gastric cancer located in the U and M portion of the stomach. He underwent total gastrectomy and Roux-en-Y reconstruction with D2 lymphadenectomy for gastric cancer. The pathological examination showed a moderately diﬀerentiated adenocarcinoma in hematoxylin and eosin stain (H&E) that was diagnosed as pT4aN2M0 pStage IIIB in accordance with the Union for International Cancer Control (UICC) tumor node metastasis (TNM) classification for gastric cancer.
He received oral administration of S-1 (80 mg/m2) for 14 consecutive days followed by 7 days of rest, every 3 weeks, as adjuvant chemotherapy. One year after gastric surgery, computed tomography (CT) imaging showed new nodules in the bladder rectal fossa and sigmoid mesocolon (Fig. ). We diagnosed these lesions as peritoneal dissemination of gastric cancer. He had no renal dysfunction; therefore, he was treated with S-1 (80 mg/m2) with cisplatin (60 mg/m2) referring to the SPIRITS trial []. After three cycles of S-1 with cisplatin, no new tumor lesions were found on CT, but the total diameter of the two peritoneal disseminations increased by 38% (Fig. ); therefore, we judged this as progressive disease in accordance with the RECIST version 1.1.
The chemotherapy treatment was changed to paclitaxel (80 mg/m2) with ramucirumab (8 mg/kg) based on the RAINBOW trial []. After six cycles of paclitaxel with ramucirumab, SUVmaxof 18F-FDG was increased to 8.9 in rectovesical excavation and 10.3 in sigmoid mesocolon (Fig. ), with no new accumulated lesion on positron emission tomography CT (PET-CT).
We then performed a trial laparotomy and observed the abdominal cavity. There were still only two peritoneal disseminated nodules, as shown in CT imaging, and peritoneal lavage cytology was negative. We partially resected the sigmoid colon, including the disseminated nodule in the mesocolon, but we could not perform a surgical resection of the disseminated nodule close to the bladder in the rectovesical excavation. The histological typing of the resected nodule of the mesocolon was the same as that of gastric cancer, and necrosis due to chemotherapy was observed in approximately 20% of the tumor. Therefore, we administered chemo-radiotherapy consisting of S-1 (50 mg/m2) and intensity-modulated radiation therapy with 66.0 Gy in 22 fractions for disseminated nodule in the rectovesical excavation.
Twelve months after chemo-radiotherapy, the SUVmaxof 18F-FDG was reduced to 2.7 in rectovesical excavation, but a new mass lesion (SUVmax: 9.4) appeared in the spleen on PET-CT (Fig. ). We judged that the accumulation of 18F-FDG in the rectovesical excavation was an inflammatory change after chemo-radiation and diagnosed metachronous splenic metastasis of gastric cancer. Splenic metastasis is known as the terminal image of cancer and since there was a history of peritoneal dissemination, we introduced chemotherapy of capecitabine (2,000 mg/m2) with oxaliplatin (130 mg/m2) [].
After ten cycles of capecitabine with oxaliplatin, there was no increase in SUVmaxof 18F-FDG in rectovesical excavation and no 18F-FDG uptake in the spleen on PET-CT (Fig. ). Therefore, we judged that it was a CR to treatment in accordance with RECIST version 1.1. Based on the observed side effect of grade 3 peripheral neuropathy due to the accumulation of oxaliplatin (Common Terminology Criteria for Adverse Events, version 5.0), chemotherapy was discontinued.
There has been no recurrence or metastasis on imaging for 15 months after the chemotherapy was concluded.


A 38-year-old male, average built, nonsmoker, occasional drinker had presented in our emergency with a history of sudden-onset severe headache. He had no history of high blood pressure but no family history of cerebral aneurysm. The patient was neurologically intact with mild neck stiffness (H and H Grade 2 and World Federation of Neurological Surgeons Grade 1). Evaluation with noncontrast cerebral computed tomography scan revealed diffuse subarachnoid hemorrhage (Fisher Grade 3). Cerebral computed tomography (CT) angiography showed a large right side M1 MCA saccular aneurysm pointing downward and laterally, arising from the dorsal wall of the vessel [Figures and ]. Aneurysm was not associated with any M1 early branch (anterior temporal or lenticulostriate arteries). Aneurysm sac's neck was 2.23 mm, and the dome was 8.20 mm × 6.23 mm. Computational fluid dynamics (CFD) showed moderate high wall pressure with low wall shear stress (WSS), vectors were divergent to the base, and streamline was disturbed. By this CFD observation, we concluded that the aneurysm had a high tendency to rupture [].
Intraoperatively, after careful Sylvian fissure dissection, proximal MCA (M1) segment large saccular aneurysm was found which was not associated with any early branch, arising from the dorsal wall of the MCA. There were multiple atherosclerotic patches over the ICA. Beside this aneurysm, no other aneurysm and bleb was found in ICA or MCA. Clipping was done successfully flushed with the parent artery without any residual neck after meticulously dissecting the aneurysm neck. Complete occlusion of an aneurysm and patency of vessels were confirmed by indocyanine green and dual-image video angiography [].
Postoperatively, cerebral CT angiography showed no residual neck or aneurysm with clip in situ []. After clipping, the patient did well with no neurological deficit and discharged with a modified Rankin score 0.


A 31-year-old single male patient presented at the accident and emergency of Al Khor
Hospital in Qatar complaining of a painless hard nodule of his left hemi-scrotum of
6 months’ duration. He reported a history of trauma of the left scrotum in his childhood
while playing cricket. The patient has no history of hypertension, diabetes mellitus, lower
urinary tract symptoms, or urethral discharge. He denied any sexual contact.
Complete blood tests and renal function tests were normal, as were the following tumor
markers: ALPHA- FETO protein 3, BCHG < 1, LDH 177. Hormone tests [luteinizing hormone
(LH), follicle-stimulating hormone (FSH), total testosterone] were also normal.
US of scrotum showed both testicles to be normal in size and echotexture. There was a
fairly well-defined hypo echoic area in the left testicular parenchyma in its middle part,
measuring approximately 10 × 9 mm in size ().
Computed tomography (CT) of the abdomen, pelvis, and thorax was conducted with contrast.
No obvious mass lesions or lymphadenopathy were detected. The patient underwent left
inguinal radical orchidectomy.
The cut surface of the testis shows a circumscribed grey white firm area measuring
1.0 × 0.8 × 0.8 cm towards the hilar region. The surrounding normal testis appears
unremarkable.
Sections show a sex-cord-stromal tumor that is attached to the tunica and characterized
by tubules, cords, and solid clusters of medium-sized polygonal cells with abundant
eosinophilic cytoplasm, ovoid nuclei, and conspicuous, and sometimes prominent,
nucleoli. Immunohistochemical (IHC) analysi showed that the tumor cells are positive
only with synaptophysin and WT–1, while negative with OCT3/4, (D2–40), Melan-A, HMBE-1,
CK AE1/AE3, SALL-4, Inhibin, Calretinin, CK 7, CK 20, Ber-EP4, CD34, CD31, CK 5/6, PSA,
Cdx-2, and CEA. Ki-67 is less than 1%. (–)
The post-operative course was uneventful, and, after 6 months of follow up, no
recurrence, no lymph node involvement or distant metastasis has been observed.


The patient was a 76-year-old female who underwent left TKA. She started
experiencing pain in both knees approximately 20 years before TKA and managed
its progression with pain medication. However, her knee pain gradually
intensified and interfered with activities of daily living (ADL). For this
reason, she underwent right TKA 4 months prior to left TKA. After right TKA, she
could walk outdoors without using a cane, but she had difficulty walking for
long distances (approximately 500 m) and climbing stairs because of pain in her
left knee. Therefore, she was hospitalized to undergo left TKA.
The surgical procedure was similar to that described in our previous report. Under general anesthesia, we made a midline skin incision and reached the
joint using a medial parapatellar approach. The patella was not replaced, and
the posterior cruciate ligament was retained. We used the Persona®
(Zimmer Biomet, Warsaw, IN, USA) implant for the femoral component and the
NexGen® Trabecular Metal™ Monoblock Tibia (Zimmer Biomet) implant
for the tibial component.
The ethics committee of Ibaraki Prefectural University of Health Sciences
approved the study (no. e204). We explained the purpose of the study to the
patient using verbal and written forms, and her written consent was
obtained.


An 87-year-old Japanese woman was transferred to our emergency room with a right hip pain after she fell in her nursing home in April 2020. In Japan, up to 5000 patients were COVID-19 positive, the beginning of COVID-19 outbreak, and one-fifth of patients were from our province at the time. She had past history of controlled arrhythmia and had no dementia. She had no history of fever, fatigue, or respiratory symptoms within the 14 days before presenting to our hospital. Physical examination on admission revealed: body temperature, 36.8°C, peripheral oxygen saturation (SpO2), 94% under room air; respiratory rate, 16 breaths/min; blood pressure, 169/66 mmHg; and heart rate, 57 beats/min. Tenderness was noted in the right Scarpa’s triangle and greater trochanter of the femur, accompanied by limited range of hip motion due to pain. Blood testing showed elevations in C-reactive protein (0.55 mg/dL) and white blood cell count (12,000 cells/mm2) with neutrophilia (80.3%) and lymphopenia (14.3%). Radiography showed right femoral intertrochanteric fracture (AO/OTA classification: type 31-A2.3) (), and only 2 nodular shadows in the upper lobe of the left lung (). Given the global COVID-19 pandemic, chest computed tomography (CT) was performed on admission and showed ground-glass opacities with consolidation in the dorsal segment of the right lower lung field. From this CT image, aspiration pneumonia was speculated as a diagnosis (). However, to confirm whether the pneumonia was due to COVID-19, qualitative real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay testing for severe acute respiratory syndrome coronavirus (SARS-CoV-2) from nasopharyngeal swabs was carried out, yielding a positive result. Femoral intertrochanteric fracture with concomitant COVID-19 infection was thus diagnosed.
Because of the infection, conservative treatment was applied to the fracture and delayed operation was planned. Rehabilitation under partial weight-bearing was started after hospital admission. On day 2, temperature increased to 37.4°C, and low SpO2 (<90%) appeared, required supplemental oxygen (1 L/min) by day 5. The patient recovered from the disease and was free of oxygen by day 10, and RT-PCR testing yielded negative results on both day 14 and day 16. Full weight-bearing was permitted from day 14. At this moment, the patient was able to ride a wheelchair and she had no hope for surgical treatment. Therefore, conservative treatment was continued. No recurrence of positive RT-PCR was seen on day 28, and she was returned to her welfare facility, able to use a wheelchair as she had before. Treatment was ongoing and she showed no other complications such as infection, dementia or deep vein thromboses. Throughout the treatment period, no cross-infection from the patient was identified in our hospital.
This case report was produced in accordance with the CARE reporting guidelines.


A 31-year-old male professional Sumo wrestler presented with right hip pain associated with a limited range of motion (ROM). His height was 190 cm, and his weight was 200 kg (body mass index [BMI] 55.4 kg/m2). Physical examination revealed a positive flexion adduction internal rotation test, flexion abduction external rotation test and dial test. The lateral center-edge angle was 19°, and the Sharp angle was 46° with a double floor at the bottom of the acetabular fossa, increased tear-drop distance, and a pistol grip deformity on the well-centered anteroposterior (AP) pelvis radiograph (). A false profile view revealed that the vertical center anterior angle was 16° (). A modified Dunn view revealed that the alpha angle was 87°, suggesting cam morphology (). Three-dimensional computed tomography scan revealed an anterior inferior iliac spine (AIIS) morphology and a cam lesion (). On magnetic resonance imaging (MRI), a T2-weighted coronal view demonstrated a high signal intensity area in the anterosuperior labrum (). Proton-density fat suppression coronal view on MRI revealed increased cartilage width (), and T2 mapping showed an increasing T2 value, suggesting articular cartilage damage.


The 1st case was an 8 month-old male infant without any birth problem who came to the emergency room (ER) with a generalized tonic-clonic type seizure after a 50 cm bedside fall. His initial mental state in the ER was semi-coma, and his pupil size was bilateral 5 mm dilatation without light reflex. Ophthalmologic examination revealed multiple retinal hemorrhages (RHs) in both eyes, and brain computed tomography (CT) scan showed acute subdural hemorrhage (SDH) on both intracranial convexity with a 1 cm left-shifted midline. After emergent bilateral fronto-temporo-parietal craniectomy, severe brain swelling progressed aggressively resulting in massive brain herniation through the craniectomy cranial window (). Electroencephalography was nearly compatible with brain death on the 9th hospital day. He died on the 19th day of hospitalization.


The 2nd case was a 7-month-old female infant who was transferred to the ER with post-ictal stuporous mentality and gingival hemorrhage. Her caregiver was a young single mother, and her boyfriend said she had no trauma history. Brain CT scans showed massive subacute SDH in the right fronto-temporo-parietal area without skull fracture. Emergent wide craniectomy on the right fronto-temporo-parietal area for brain decompression and evacuation of SDH was done. She underwent tracheostomy on the 21th postoperative day. A ventriculoperitoneal shunt was performed on the 49th postoperative day and cranioplasty on the 133th postoperative day (). She was in the vegetative state at the time of transferring to the long-term care facility on the 254th postoperative day.


The 3rd case was a 6-month-old female who came to the ER with respiratory arrest after febrile convulsion. Her parents performed cardiopulmonary resuscitation about 3 minutes. Brain CT scans revealed acute SDH in both fronto-temporo-parietal areas with severe brain swelling and multiple skull fractures (). Her parents denied any history of head trauma but the degree of injuries was severe compared to the statement. Emergent craniectomy for brain decompression and hematoma evacuation was performed. On 5th day in the hospital, single photon emission CT of the brain was compatible with brain death. He died on the 24th day of hospitalization.


The last patient was a 2-month-old male infant, who came to the ER with respiratory arrest during breast feeding. The initial mental status in the ER was semi-comatous with bilateral 5 mm pupil dilatation without light reflex. According to his parents, there was no history of head trauma. Ophthalmologic examination revealed diffuse RHs and macular hemorrhages in both eyes, multiple periosteal reaction in simple extremity x-rays, and brain CT showed acute SDH in the bilateral fronto-temporo-parietal area (left side dominant) and tentorial hemorrhage (). He underwent emergent burr-hole drainage in the right parieto-occipital area. He received ventilator care in the intensive care unit in a vegetative state on the 199th postoperative day.


A 57-year-old male patient was admitted to our department with continuous back pain without any traumatic episode. The pain persisted for several months but progressively worsened with activity or while in the standing position with relief when lying down. A computed tomography (CT) scan and magnetic resonance imaging (MRI) was performed to rule out a compression fracture. The CT revealed a characteristic ‘polka dot’ pattern of the trabecular thickening involving the whole T12 vertebral body. The MRI showed the mass was high signal intensity on the T2 weighted images and low signal intensity on the T1 weighted images without epidural extension (). These findings resulted in the diagnosis of a vertebral hemangioma. Conservative treatment, including analgesic and anti-inflammatory drugs, physiotherapy, and epidural steroid injections, was performed. However, the patient complained of progressively worsening back pain over the following 2 months and re-visited our institute.
The CT and MRI took 2 months later, demonstrated an expansile mass involving the vertebral body and the posterior element with epidural extension and cord compression at the T12 (). A preoperative embolization and vertebrectomy with reconstruction are recommended for aggressive vertebral hemangiomas. However, given the patient's intact motor power, a less invasive procedure was performed. The patient underwent intraoperative vertebroplasty and percutaneous screw fixation.
The patient received about 4 mL's of polymethylmethacrylate injected into the T12 vertebral body, followed by percutaneous screw fixation to prevent tumor growth and to enhance stability (). The pathological diagnosis was consistent with epithelioid hemangioendothelioma, which is an aggressive vertebral hemangioma (). After surgery, the patient's back pain improved dramatically, and he was transferred to the hemato-oncological department for low-dose radiotherapy. No further tumor growth was observed over 4 years after the procedure.


A 62-year-old male patient presented to our outpatient department with asymptomatic violaceous lesion in the right retroauricular area for 6 months. He noticed similar smaller size lesion on the left retroauricular area for 1 month. Physical examination revealed hyperpigmented tumid plaque of size 1–4 cm studded with whitish to yellowish milia-like cysts and open comedones [Figures and ]. Examination of hair, nail, and oral mucosa revealed no abnormality. The patient denied any history of trauma, bullous lesion, use of any topical treatment or hearing aid. The patient was a known case of hypertension and diabetes since 10 years and was on treatment. Based on the clinical examination, the differential diagnosis of milia en plaque, LPFT, and nevus comedonicus was considered. Histopathological examination of biopsy taken from retroauricular lesion revealed epidermis showing focal hypergranulosis and basal cell layer vacuolization, dense infiltration with lymphocytes and melanophages in dermis. Moreover, at places, epidermis showed follicular plugging, dermis showed keratin-filled cysts and dense lymphocytic infiltration around cystic spaces [Figures -]. Routine laboratory investigations were within normal limits. Serology for hepatitis B and C virus was negative, and thyroid function test was within normal limit. Based on the clinical and histopathological examination, we reached a final diagnosis of lichen planus follicularis tumidus involving bilateral retroauricular areas. We put him on oral prednisolone 0.5 mg/kg body weight with slow tapering. The patient showed mild improvement after 4 weeks of treatment in the form of decrease in tumidity of lesion.


A 51-year-old female patient with no medical history presented to the Endodontic Department of Jilin University Stomatological Hospital with a complaint of persistent painful swelling at the left mandibular posterior buccal area.
Upon history-taking, she revealed that she underwent a tooth-filling procedure on the left mandibular posterior area 10 years ago. For the past 3 mo, she had been experiencing slight pain, discomfort, and swelling over the affected area. She took a type of anti-inflammatory drug, and the pain decreased. She was unsure of the type and dosage of the drug she took. However, for the past 1 mo, the pain and swelling recurred. It was worse in severity and not relieved by the same anti-inflammatory drug she took before.
She had no significant medical history.
The external examination of the face and palpation for lymphadenopathy did not show any significant abnormality. However, a composite resin restoration in the left mandibular first molar (tooth #36) was detected upon the intraoral examination. There was no response on the pulp vitality test, but the patient complained of obvious pain upon percussion. Furthermore, there was slight gingival congestion and swelling at the buccal area of tooth #36 with exudate extrusion upon the application of pressure. The periodontal examination showed a pocket of 6 mm depth in the mesiobuccal (MB) aspect of tooth #36, with a grade I tooth mobility. The intraoral examination also reveals a fair oral hygiene status with no signs of trauma or malocclusion.
No laboratory tests.
The preoperative radiograph (Figure ) revealed an occlusal filling close to the pulp cavity in tooth #36. A large area of radiolucency in the apical area was observed along the periodontal lining. It was associated with a bifurcation involvement. Cone beam computed tomography (CBCT) imaging showed that the apical, periodontal, and root bifurcation areas were all connected. Furthermore, a high level of resorption of the buccal bone plate in the tooth #36 region (Figure ).


A 37-year-old female was admitted to the First Affiliated Hospital of Wenzhou Medical University in June 2019 suffering from severe exertional dyspnea that had progressed over the preceding 5 years. Oxygen inhalation was sufficient to relieve these symptoms.
The patient had suffered from exertional dyspnea for 5 years. Pneumothorax had also occurred twice within 5 years, with two surgeries having been performed to remove bullae.
This patient had been diagnosed with central diabetes insipidus (DI) in May 2007 associated with polydipsia and polyuria, and had been treated via radiotherapy, desmopressin acetate 300 mg/d, and bromocriptine mesilate 0.625 mg/d. The patient also had elevated levels of prolactin (PRL 941 mIU/L; normal range: 70.81-566.46 mIU/L). Magnetic resonance imaging (MRI) of the sella region detected posterior pituitary and pituitary stalk lesions (Figure ).
In June 2014, biochemical analysis revealed the presence of cholestasis (alkaline phosphatase, ALP 729 U/L; gamma-glutamyl transferase, γ-GT 319 U/L), as well as elevated levels of transaminases. This patient had been diagnosed with autoimmune hepatitis that had been unsuccessfully treated with a combination of methylprednisolone 4-8 mg/d and mycophenolate mofetil 1000 mg/d. The patient was also found to have elevated bilirubin levels in February 2015 (total bilirubin 58 μmol/L, direct bilirubin 45 μmol/L). An MRI analysis of the liver revealed the presence of hypointense lesions, while magnetic resonance cholangiopancreatography (MRCP) revealed local stenosis of the hepatic duct (Figure ). An ultrasound-directed liver biopsy was performed in April 2019, with subsequent histological examination suggesting the presence of chronic hepatitis.
Physical examination upon admission detected no positive signs.
Blood gas analysis with 35% oxygen concentration revealed a PaO2 of 91.4 mmHg (normal range: 80-100 mmHg), a SaO2 of 97.4% (normal range: 91.9%-99.0%), and a P(A-a)O2 of 105.2 mmHg (normal range: 5.0-30.0 mmHg).
A computed tomography (CT) scan revealed the presence of cysts in both lungs. The patient exhibited an enveloping pneumothorax in the lower lobe of the right lung which may be associated with the prior pulmonary bullae resection and pleurodesis that had been conducted in 2014. During the previous 5 years, cysts in the upper and middle lungs had grown significantly, and lower lung involvement had begun to manifest (Figure ).


A 74-year-old woman presented to a primary care physician with 10 days of mild, non-exertional pleuritic chest pain on deep inspiration and episodic low-grade subjective fever. She denied cough, shortness of breath, lower extremity symptoms, and urinary tract symptoms. She was haemodynamically stable, with normal vital signs as follows: blood pressure 110/69 mmHg, pulse 79 b.p.m., temperature 36.7°C, a normal respiratory rate, and oxygen saturation 98% on room air. Her body mass index was 20 kg/m2. Her physical examination was unremarkable, including heart, lung, and extremity evaluations.
The patient had fallen off a ladder 9 weeks earlier and sustained a tibial plateau fracture, which was treated with open reduction and internal fixation. She had completed her course of thromboprophylaxis without complication. At the time of presentation, she was recovering at home with her niece. She had no chronic medical conditions except osteoporosis and had no history of cardiac, pulmonary, renal, or venous thromboembolic disease.
Blood tests and a urinalysis were completed that day. The urinalysis was normal and the complete blood count and estimated glomerular filtration rate were within normal limits. The D-dimer level was elevated at 1653 ng/mL (age-adjusted normal <740 ng/mL). The physician ordered a same-day CTPA at the on-campus radiology suite, but the patient preferred to go home to rest and wanted to defer the imaging for 3 days. The physician explained that the delay was not optimal but would suffice if the patient promised to go to the emergency department if she developed new or worsening symptoms. She agreed. She was not treated with pre-emptive anticoagulation.
The CTPA was performed as re-scheduled and identified a lobar embolus without signs of right ventricular dysfunction. The physician called the patient, explained the results, and advised her to report to the emergency department for evaluation and treatment. The patient, however, felt this was unnecessary because she was feeling better, and she requested comprehensive clinic-based care. The physician said he would call her back after evaluating her eligibility.
The on-call pulmonologist agreed that the patient met the criteria for outpatient care. Her vital signs were all normal. Her PE Severity Index (PESI) score and class of 74 points and class II, respectively, correlate with a low 30-day all-cause mortality., She also lacked evidence of right ventricular dysfunction on imaging, a criterion of the 2019 European Society of Cardiology (ESC) PE guidelines (). Additionally, she owned a phone, had ready access to transportation, and had strong family support, all of which favoured outpatient management.
Her physician consulted the healthcare system’s pharmacy-led anticoagulation management service about medication options. On their advice, he prescribed a 5-day course of subcutaneous enoxaparin (60 mg every 12 h) followed by oral dabigatran (150 mg twice daily) for 3 months, which were the medical group’s formulary recommendations at the time. The physician communicated the treatment plan to the patient and her niece, along with basic education on anticoagulation, the expected disease course, and the indications to seek medical attention.
The anticoagulation pharmacist called the patient later that afternoon to continue patient and family education. The patient was seen in the clinic 2 days later and had a phone appointment with her primary care physician 1 week following that. She did not experience a recurrence or complications in the ensuing 3 months, after which the anticoagulation therapy was discontinued. Her D-dimer level shortly thereafter was within normal limits.


A 50-year-old woman with a history of patch closure and resection of a ruptured right SVA 32 years earlier was referred to our hospital due to chest pain on exertion of 1 month duration. In the years after SVA surgery, she had been followed up without recurrence until the age of 30, after which her follow-up hospital visits had been discontinued. She had no history of atherosclerotic disease, connective tissue disease, or chest trauma and no family history of connective tissue disease or aortic aneurysm. On physical examination, a systolic murmur with an intensity of III/VI at the apex and an incision scar following a median sternotomy, but no physical features of connective tissue disease, were seen. Electrocardiography showed a sinus rhythm and slight ST depression in the inferior leads. Chest X-ray revealed bulging of the right cardiac border, which was not obvious on the images obtained 3 years earlier (). Echocardiography revealed an unruptured SVA of the non-coronary sinus with moderate aortic regurgitation (AR), severe mitral regurgitation (MR) due to floppy mitral valve, and severe tricuspid regurgitation (TR) presumably due to compression by the SVA (, , Video S). Three-dimensional reconstruction of the cardiac computed tomography (CT) images showed a large non-coronary SVA and severe narrowing of the right coronary artery (RCA). In addition, the transverse and sagittal images revealed that the RCA was compressed between the SVA and sternum (, , Video S). Adenosine triphosphate stress myocardial perfusion imaging (MPI) identified reversible ischaemia in the inferior segment ().
The patient underwent surgical intervention for the recurrent SVA. After patch closure of the SVA orifice, water testing revealed residual TR due to an enlarged tricuspid annulus. Tricuspid valve annuloplasty was performed (Medtronic, Contour 3D). Because the MR was thought to be due to a functional prolapse, mitral valve annuloplasty was performed using a Memo 3D ring. Subsequent water testing demonstrated no residual MR. After the aorta had been unclamped, transoesophageal echocardiography revealed severe AR, and aortic valve replacement was performed using an 18 mm ATS-Advanced Performance. Intraoperatively, no marked atherosclerotic changes in the RCA were observed. The pathology report described a loss of medial elastic fibres and fibrous thickening but no inflammation or myxomatous changes in the aneurysmal wall. Post-operative echocardiography showed successfully repaired SVA and AR, trivial MR, and mild to moderate TR (, , Video S). Post-operative CT imaging demonstrated the thrombosed SVA and intact RCA (), but no residual ischaemia was seen on the MPI study (). The patient was discharged home and has been asymptomatic during the follow-up period. At the 3 years after surgery, echocardiography and CT imaging demonstrated no recurrence of SVA.


A 17-year-old male initially presented with chief complaints of a fever (at 40.2°C), headache, dyspnoea on effort, and cervical lymphadenopathy. Three days later, he was diagnosed with KD based on the appearance of polymorphous rash, peripheral oedema, cracked lips, bilateral conjunctivitis, and a swollen and bumpy ‘strawberry’ tongue. He had no noteworthy previous medical history or family history. The antinuclear antibody level was below 1:40 and the rheumatoid factor was negative. Both the myeroperoxidase-anti-neutrophil cytoplasmic antibody (ANCA) and proteinase3-ANCA levels were within normal limits and no suspicious findings regarding other immune diseases were observed. He was hospitalized at this time and received a single dose of intravenous immunoglobulin (IVIG; 2 g/kg) together with oral aspirin therapy (30 mg/kg/day) in an effort to prevent the development of a coronary artery lesion (). Shortly thereafter, his blood pressure dropped to 74/38 mmHg and his heart rate increased to 133 beats/min. Chest radiograph was notable for bilateral lung congestion and cardiac enlargement (cardiothoracic ratio = 59%). An electrocardiogram included ST-segment elevation in V2–4 precordial leads (). At this time, his ejection fraction had dropped to 10% (), and accumulated pericardial fluid was detected in an echocardiogram. Likewise, plasma levels of brain natriuretic peptide (BNP) increased markedly to 1.031 pg/mL (normal < 18.4 pg/mL); serum levels of troponin-T were mildly elevated at 0.093 ng/mL (normal < 0.014 ng/mL). These findings suggested acute myocardial injury in association with KD. Emergency coronary angiography was performed, followed by right heart catheterization and endomyocardial biopsy under inotrope infusion, intra-aortic balloon pumping (IABP), and peripheral veno-arterial extracorporeal membrane oxygenation (V-A ECMO) support. He had no valvulitis, but his age-adjusted haemoglobulin level was normal and platelet count was preserved (160 000/mm3). In addition, blood cultures showed no bacterial involvement and plasma endotoxin levels were within normal limits. He was diagnosed as KDSS as per the recently proposed criteria.,
Pathological findings in the endomyocardial biopsy specimen are shown in . Inflammatory cell infiltrates were detected in the myocardial interstitium in association with mild fibrosis, consistent with a diagnosis of myocarditis. Immunostaining revealed a small number of CD3+, CD4+ or CD8+ and CD20− small lymphocytes together with a few CD68+ macrophages. The serological analysis with paired serum samples did not reveal any viral involvement. No stenosis or aneurysms were noted at the coronary arteries. As his cardiac index had decreased to 1.6 L/min/m2, we treated his IVIG-resistant KDSS and myocardial inflammation with pulse IST using methylprednisolone 1000 mg/day for 3 days; oral steroids were added because the troponin-T level remained high on hospital Day 4 (). Left ventricular systolic function had slightly improved by hospital Day 5 and had normalized by hospital Day 7 (), with a left ventricular ejection fraction (LVEF) of 55%. V-A ECMO was discontinued on hospital Day 7 as was IABP support on hospital Day 8. During right heart catheterization, cardiac index, and pulmonary artery wedge pressure was maintained at 3.5 L/min/m2. A repeat coronary angiography on hospital Day 30 revealed no abnormal findings and notably no coronary aneurysms. At follow-up 6 months after discharge, echocardiography was notable for normal systolic function (LVEF 66%). Troponin-T and plasma BNP level were within normal range without oral steroid therapy (0.005 ng/mL and 7.0 pg/mL, respectively).


A 35-year-old male drywall installer presented with 2 years of progressive left upper extremity weakness, numbness, and hand clumsiness. Neurologic examination demonstrated 4-/5 strength of the left hand intrinsic muscles, decreased sensation to light touch in the left hand, and hyperreflexia of the left upper extremity. Electromyography and nerve conduction testing demonstrated only mild incidental bilateral ulnar neuropathy across the elbow. Magnetic resonance imaging (MRI) of the cervical spine demonstrated cervical spinal cord expansion with T2 hyperintensity at C4-C5. There was an associated defect of the bony posterior elements with projection of the neural elements into the dorsal subcutaneous soft tissue []. At this point, he was referred to our institution where only upon detailed questioning did he mention that he had neck surgery just after birth, but he did not know what was done. This additional history allowed the diagnosis of retethering of a cervical myelomeningocele. A cervical detethering operation was recommended.
He then also reported that he routinely shaved a patch of lower back hair, but denied bowel, bladder, or lower extremity dysfunction. This prompted an MRI of the lumbar spine which demonstrated underlying diastematomyelia with a low-lying conus []. His lower extremity and sacral examination were normal. Because the diastematomyelia was asymptomatic in this adult patient at final height, observation was recommended.
After satisfactory induction of general endotracheal anesthesia, the patient was positioned prone on gel rolls, and his head was fixed in Mayfield pins in neutral position. Neuromonitoring with somatosensory evoked potentials (SSEP), motor evoked potentials, and electromyography was established. The prior curvilinear midline incision was marked and slightly extended superiorly and inferiorly.
The superior portion of the incision over the last rostral intact lamina was opened sharply and carried down to the fascia using blunt dissection. Progressing along the fascia from superior to inferior, the overlying soft tissue was opened. The myelomeningocele sac was identified and dissected circumferentially as it passed through the fascia. The sac was then separated from the overlying soft tissue [].
The fascia was opened rostral and caudal to the myelomeningocele sac. The rostral (bifid) and caudal (hemi) dysplastic spinal lamina were removed using Kerrison rongeurs. The exposed native dura was contiguous with the myelomeningocele sac [ and ]. Intraoperative ultrasound was used to confirm adequate bony exposure and identify dorsal subarachnoid space for dural opening.
Under microscopic magnification, the spinal cord dura was incised rostral to the myelomeningocele. Progressing caudally, the dorsal spinal cord was found to be tethered to the dura by thick arachnoid bands. These were divided as they were encountered. The dural opening eventually extended into the myelomeningocele sac. In the sac was a dorsal projection of the cervical spinal cord approximately the same size as the cervical spinal cord. It was freed circumferentially from its dural attachments. The dorsal projection terminated in dysplastic spinal cord that fused with the overlying dural sac []. At the transition to dysplastic spinal cord, electrical stimulation did not result in a response in the neuromonitoring. The dorsal projection was sectioned at this location and the pial closed []. The detethering was then continued inferiorly to the native spinal cord. Eventually the point of last attachment was sectioned, and the cord was free and lax.
The remaining stump of dorsal projection still needed to be addressed. Sectioning the dorsal projection closer to the native spinal cord was avoided due to fear of transiting neural tracts within the projection. Left alone, the stalk came to a resting position along the dorsal surface of the rostral spinal cord []. In this position, there was sufficient redundant dura to close without compressing the projection or the native spinal cord. This was verified with the ultrasound before and after the dura was closed; there was ample subarachnoid space surrounding the neural elements.
The dura and overlying soft tissue were closed primarily in a watertight fashion. The neuromonitoring signals at the end of the operation were stable compared to the beginning. In fact, the left arm SSEP was mildly improved. There was no significant neuromonitoring signal change throughout the surgery.
The dysplastic portion of the dorsal projection along with its fused overlying dura was examined []. Hematoxylin and eosin stained sections showed band-like collections of neuroglial tissue and meninges within a background of fibrosis, collagen fiber bundles, and disorganized smooth muscle. Scattered dermal appendages were also identified.
On postoperative day 1, the patient reported improvement in his left upper extremity weakness and numbness. At 1 month follow-up, he reported continued improvement in his symptoms. He had some residual altered sensorium of the left hand, but improvement in his intrinsic hand muscle strength and no further pain, paresthesia, or clumsiness. He had returned to work without special accommodation. At 4 months follow-up, he had regained full strength in his left hand, and MRI showed a successful detethering without neural compression []. The diastematomyelia remained asymptomatic and is being observed.


A 43-year-old Caucasian male presented with 5 months of persistent posterior cervical neck pain radiating to the right shoulder, accompanied by paresthesias and right upper extremity radiculopathy. Although both his motor and sensory exams were intact, he was diffusely hyperreflexic (3+ bilateral biceps, brachioradialis, triceps, patella, and ankles [two beats of unsustained clonus in his right foot]) with bilateral Babinski signs. Hoffman’s signs were negative bilaterally.
The cervical MRI demonstrated a T1 isointense, T2 hyperintense, enhancing intradural, extramedullary mass measuring 2.4 × 1.4 × 1.1 cm at the C5–C6 level []. It was eccentrically located to the right, compressing the cervical spinal cord without abnormal hyperintense T2 spinal cord signal. The predominant differential diagnoses included a benign nerve sheath tumor versus meningioma.
He underwent a cervical laminectomy for gross total microsurgical resection of the tumor. The tumor was intradural and completely extramedullary; it appeared to arise from a C6 nerve rootlet. Gross total resection of the tumor was achieved and the entire lesion for sent for pathologic analysis.
The pathologic findings were most consistent with a PXA (WHO Grade II). The tumor was a well-circumscribed neuroepithelial neoplasm arranged in fascicles, sheets, and nests []. The tumor cells were variably pleomorphic and occasionally showed an epithelioid, xanthomatous, or ganglionic appearance. Scattered eosinophilic granular bodies and focal collections of perivascular lymphocytes were also noted. Up to 4–5 mitoses/10 high-power field were counted. Immunohistochemistry demonstrated GFAP, SOX10, synaptophysin, S100, SOX10 (red), and CD34 reactivity in most of the neoplastic cells. Staining with inhibin, NSE, MelanA, HMB45, NeuN, and H3K27M was negative. ATRX and INI1 were retained. No IDH1R132H mutation was detected. The reticulin stain highlighted only the blood vessels. A mutation of V600E in the BRAF gene was not detected on PCR. The DNA methylation analysis revealed no additional information. No reportable germline and somatic variants were detected with the PBTP Next-Generation Sequencing panel.
The patient did well postoperatively, with improvement in his preoperative radicular pain and paresthesias. He was discharged home on postoperative day 2. In addition, he returned to work part-time 1 month following surgery, noting only mild right cervical paraspinal discomfort with activity.
The postoperative MRI demonstrated no residual disease, and the MRI of the brain, thoracic, and lumbar spine showed no other lesions. On follow-up MR 7 months later, the tumor had not recurred [].


A 50-year-old Afro-Caribbean woman, with a history of hypertension, reactive arthritis and a previous episode of myopericarditis in 2012, presented to the emergency department with a 4-day history of central chest pain, which was made worse on lying flat and on deep inspiration. The patient had regular medications including 10 mg lisinopril and 10 mg amlodipine per day for hypertension, and 2.5 mg tibolone per day for suppression of perimenopausal symptoms. She did not complain of cough or breathlessness. She had a blood pressure of 116/74 mmHg, a pulse rate of 85 b.p.m., oxygen saturation of 97% on room air and she was afebrile. Examination findings were normal. Laboratory tests () showed a normal haemoglobin level, white cell count and platelet count. The patient had a lymphopenia at 0.63 × 109 cells/l (normal 1.5–4.5 × 109 cells/l), her C-reactive protein (CRP) level was elevated at 11 mg/L (normal <5 mg/L) and her high-sensitivity troponin T (hsTnT) was elevated at 77 ng/L (normal <14 ng/L).
An electrocardiogram (ECG) showed poor R-wave progression and small QRS complexes (). An echocardiogram showed a trivial anterior pericardial effusion with good biventricular function. A chest radiograph was normal. The patient was admitted under the cardiology team with a presumed diagnosis of myopericarditis based on her symptoms and laboratory results. She was started on colchicine (500 μg twice daily) and ibuprofen (400 mg three times daily) as per conventional therapy for myopericarditis.
The patient continued to complain of chest pain on Day 2. Given that the symptoms had not improved on 1200 mg per day of ibuprofen, 30 mg per day of prednisolone was started as additional therapy with the aim of settling the myopericardial inflammation. By Day 3, the patient’s chest pain had not improved, and so a computed tomography (CT) scan of the patient’s thorax was obtained to exclude possible alternative diagnoses which could explain the patient’s symptoms, or to confirm the diagnosis of unresolving myopericardial inflammation and identify consistent features such as pericardial thickening and calcification. The CT thorax showed a small pericardial effusion and non-specific bronchocentric ground-glass opacities in the left lower zone which was reported as being suspicious for COVID-19 (). At this time, the patient had a peak temperature of 37.5°C. An oropharyngeal swab tested positive for SARS-CoV-2.
On Day 5, the patient began to experience proximal leg weakness effecting hip flexors and knee extensors, with tenderness over both quadricep muscles and associated lethargy. Oral codeine phosphate (30 mg) was started and administered four times daily for analgesia. On Day 6, a serum creatinine kinase (CK) was measured to diagnose myositis given the ongoing leg weakness, and this was found to be elevated at 6432 U/L (normal value 25–200 U/L). Intravenous 0.9% sodium chloride was initiated to avoid rhabdomyolysis-associated acute renal injury. Repeat hsTnT and CRP were measured at 106 ng/L and 58 mg/L, respectively. On physical examination, the patient had 3/5 power of both quadricep muscles. A rheumatological review was sought and myositis was clinically diagnosed. A magnetic resonance imaging (MRI) scan of both thighs was suggested. It was advised that the patient continue 30 mg prednisolone daily for the next 7 days. The patient continued to experience progressive weakness and tenderness of both quadricep muscles until day 8, at which point the CK peaked at 32230 U/L. An MRI of both lower limbs confirmed features of diffuse myositis with symmetrical appearances involving the anterior, medial and posterior muscle compartments of the thighs with subcutaneous oedema ().
Her autoimmune screen (ANA and ANCA) and hepatitis B, C, and HIV serology were negative. There were no significant changes of either the ECG or echocardiogram when compared with those taken on admission. A cardiac MRI showed normal left and right ventricular function, with possible evidence of myocardial oedema in the basal inferoseptum, in keeping with myocarditis, as well as a 16 mm circumferential pericardial effusion ().
On day 12, a CK was measured at 4922 U/L and a CRP at 14 mg/L. The patient’s symptoms of leg pain and weakness improved. On day 13, the patient’s leg and chest pain had resolved. The lower limb weakness was still improving, and the patient was discharged with a 3-month course of 500 μg twice-daily colchicine and 400 mg three times daily ibuprofen, and 7 days of 30 mg once-daily prednisolone. A telephone follow-up was carried out 2 weeks after discharge which confirmed that the patient had remained symptom free. The lower limb weakness normalized within 48 hours of discharge. The patient will have a repeat cardiac MRI 4 weeks after discharge to assess resolution of myocardial oedema and ensure there has been no reduction in cardiac function.


A 28-year-old female patient with type 1 diabetes was diagnosed at the age of 13 (2004) and at the age 22 (2012) with onset of proteinuria (1.5 g/day) and eGFR 90 ml/min/1.73 m2; therefore DMT1 treatment was started using a personal insulin pump. In 2015 the patient was admitted to the Endocrinology Clinic due to weight gain and massive swelling of lower limbs. Laboratory tests revealed microcytic anemia (Hb 10.2 g/dl), leukopenia (3790/ml) with lymphopenia (1000/ml), hypoproteinemia with dysproteinemia (total protein – 5.7 g/dl, albumin – 3.18 g/dl), proteinuria (6.5 g/day), and hypercholesterolemia. Renal function parameters remained normal.
Additionally, immunological studies showed a reduced concentration of complement components C3 and C4, antinuclear antibodies (ANA) presented in titer 1 : 2560 with speckled staining pattern, whereas pANCA and cANCA antibodies were absent. In abdominal ultrasound, the kidneys had normal size and structure. The patient also had an episode of deep vein thrombosis in the left upper limb.
At the age of 26 (2016), the patient was admitted to the Department of Rheumatology and Systemic Connective Tissue Diseases. The patient denied skin, mucosal and joint symptoms. The immunoassay tests were repeated: ANA 1 : 2560, speckled staining pattern, SS-A (++), SS-B (+++), Rib P (++) present in the ENA panel, anti-dsDNA borderline, anti-cardiolipin antibodies present in the IgM class – aCL-IgM (160.4 MPL; norm < 20 MPL) and in the IgG class – aCL-IgG (38.1 GPL; norm < 20), lupus anticoagulant was absent, but Factor V Leiden mutation was present.
Based on the clinical image and the results of additional tests, SLE was diagnosed. Hydroxychloroquine at a dose of 200 mg/day was recommended for treatment. Three months later, the anti-phospholipid antibody assay was repeated. High-aCL-IgM and aCL-IgG were detected, and anti-beta2-glycoprotein I antibodies in the IgM and IgG class (anti-b2-GPI IgM and IgG) were present.
Antiphospholipid syndrome (APS) was diagnosed, and warfarin anticoagulation was initiated. Due to the unclear etiology of nephropathy (diabetic? in the course of SLE? APS?), the patient was qualified for kidney biopsy. The pathomorphological image corresponded to class IV lupus nephropathy. Glucocorticosteroid and cyclophosphamide (CYC) pulses were used in the Euro-Lupus regimen. After 3 γ CYC administration, partial remission of lupus nephropathy was achieved: total protein and albumin levels were normal, and proteinuria decreased (3.2 g/day). Mycophenolate mofetil (MMF) at a dose of up to 2 g/day was recommended for maintenance of remission, hydroxychloroquine, and anticoagulant therapy were continued. After achieving partial remission, the MMF dose was reduced to 1 g/day. Since then, the patient has remained without clinical symptoms of SLE: proteinuria < 1 g/day, and eGFR 78 ml/min/1.73 m2 ().


A 72-year-old woman was admitted to our hospital for abdominal pain and difficulty defecating. She had a history of colorectal cancer and had undergone laparoscopic partial resection of the transverse colon 4 years earlier. A functional end-to-end anastomosis was performed for colonic reconstruction in the patient, who was postoperatively diagnosed with adenocarcinoma, type I, 35 × 30 mm, SS, N1, H0, P0, M0, stage IIIa, and there was no recurrence during postoperative follow-up.
Computed tomography (CT) revealed sac-like dilation of the functional end-to-end anastomosis and a large, multilayered, fecal mass in the transverse colon (axial, Fig. ; coronal, Fig. ). There was no dilation of the intestinal tract on the oral side of the anastomosis, and fecal ileus was ruled out. The patient underwent CS as well as a Gastrografin enema examination through CS, which revealed a 10 × 8 cm calculus (Fig. ), an anastomotic ulcer (Fig. ), a blind pouch (Fig. ), and an end-to-end anastomosis (Fig. ) in the transverse colon. Despite the absence of hallmark symptoms of blind pouch syndrome, i.e., anemia, diarrhea, and weight loss, she was diagnosed with blind pouch syndrome-associated enterolithiasis and underwent colonoscopic treatment. Histopathological examination of a biopsy specimen from the anastomotic ulcer showed chronic inflammatory cell infiltration (Fig. ).
Colonoscopic treatment using snares and alligator forceps was performed during the ensuing 4 days, which led to nearly all of the calculus being crushed and removed. A bowel cleanser was administered, and CS with Gastrografin was performed 3 days after treatment, which showed that the enterolithiasis had disappeared and the anastomotic ulcer had improved (Fig. ). The patient was discharged 1 week after admission due to improved abdominal pain. With defecation control with laxatives in place, the patient's course was uneventful for 3 months after treatment.
Retrospectively, CT performed at postoperative 5 and 8 months revealed fecal stasis (Fig. ) and blind pouch formation (Fig. ) at the anastomosis site, respectively.


A 44-year-old woman presented with progressive kyphosis for more than 10 years and low back pain in the past 2 years.
It had been about 10 years since she suffered from kyphosis, just after she gave birth. After long standing and fatigue, she began to feel low back pain, and her height became shorter after getting up in the morning, but she had not been diagnosed and treated. She suffered from severe inferiority due to deformity as well. In the last 2 years, her pain was gradually aggravated. Neurofibromatosis was diagnosed at a local hospital many years ago.
The patient had no previous medical history.
The patient was 144 cm in height and had a weight of 40 kg. A mass of café-au-lait spots and neurofibromas can be found over her body. She presented thoracolumbar angular kyphosis, but no spinal cord damage or neurological dysfunction (Figure ).
The bone mineral density is as follows: Femoral neck, 0.747 g/cm2; and T-score: -1.8. The bone mass of the femur decreased.
Preoperative computerized tomography (CT) and magnetic resonance imaging examinations showed rotatory subluxation of L2 vertebra, spontaneous fusion of T12-L4 vertebrae, thin pedicles of L1-L5, expansion of dural ectasia, and spinal cord located in the concave side (right) (Figure ).


A 73-year-old woman with symptoms such as palpitation, dyspnea, and acratia for 2 d was referred to the Emergency Department of our hospital on May 28, 2019.
The patient was diagnosed with essential thrombocythemia (Janus kinase 2 V617F mutation) 1 year ago, and the symptoms of palpitation, dyspnea, and acratia were detected within the past 2 d. The routine blood test showed that her platelet count was 1205 × 109/L, and its reference range (RR) was 125-350 × 109/L. She was transferred to the Hematology Department for further treatments on May 29, 2019.
The patient had a history of hypertension for 8 years. Renal insufficiency and cerebrovascular stenosis were diagnosed 4 years ago; however, her blood pressure was in control. She had aspirin irregularly, and the drug was discontinued due to purpura.
Slight pitting edema on both legs was revealed upon physical examination. Other remarkable abnormalities were not found. Vital signs were within normal limits, with a temperature of 36.7 °C, heart rate of 80 beats/min, respiratory rate of 18 breaths/min, and blood pressure of 120/63 mmHg.
Repeated routine blood test showed white blood cell count of 51.4 × 109/L (RR: 3.50-9.50 × 109/L), hemoglobin of 60 g/L (RR: 115-150 g/L), and platelet count of 1460 × 109/L. Blood biochemistry tests showed that the patient suffered from hyperkalemia (potassium: 7.50 mmol/L, RR: 3.60-5.00 mmol/L) and renal failure (urea nitrogen: 16.63 mmol/L, RR: 2.50-6.10 mmol/L; creatinine: 579 μmol/L, RR: 40-97 μmol/L; uric acid: 2578 μmol/L, RR: 149-446 μmol/L; estimated glomerular filtration rate (eGFR): 8.88 mL/min, RR: > 90.00 mL/min). Twelve lead resting electrocardiography results were normal.
The patient was diagnosed with essential thrombocythemia, chronic renal failure, and hyperkalemia.


A previously healthy 24-year-old woman presented with a headache of two days duration. She was referred to the emergency room of our hospital because she had a history of slip-down in a bathroom two days previously. Precontrast brain computed tomography (CT) revealed a small amount of extra-axial hemorrhage at the right frontotemporal region (). Skull magnetic resonance images showed a slightly rim-enhancing lesion invading right sphenoid bone. Differential diagnoses included vascular pathologies such as hemangioma and other tumorous conditions. The skull tumor was removed using a navigation system and cranioplasty of the right frontotemporal area was performed using bone cement. Inferolateral temporal dura over the lesion had been focally disrupted, but no gross leakage was observed. After exposing the right temporal fascia and muscle, the lateral wall of the right orbit, zygoma, and a thinned portion of the bone at the pterygoid process were drilled. Removal of the hematoma exposed a multiseptated cystic cavity ().
Intraoperative frozen biopsy was performed on the cystic portion of right sphenoid bone, and subsequent intraoperative squash cytology revealed moderate cellular smears composed of sheets or clusters of epithelioid cells in an inflammatory cell– rich background (–). Histologically, singly scattered or clusters of round-to-elongated tumor cells were found in sclerotic bone (). Tumor cells with indistinct cell borders were observed in clusters forming meningothelial whorls and had centrally-placed small round and bland nuclei with or without nucleoli. Prominent hemorrhage was present. Individual tumor cells showed abundant eosinophilic cytoplasm with an occasional vacuolated appearance and cytoplasmic clearing resembling oligodendroglioma (). Neutrophils were abundant (, left). There was marked perivascular hyalinization and stromal sclerosis (, right). Mitotic counts were up to 1 per 10 high power fields, necrosis was absent, and occasional atypia was observed. Tumor cells invaded the thick dura mater. They were positive for CD56 (1:100, CD564, Novocastra, Newcastle upon Tyne, UK), CD99 (prediluted, 12E7, Dako, Glostrup, Denmark), INI-1 (1:200, 25/BAF47, BD Bioscience, San Diego, CA, USA), vimentin (1:100, V9, Dako) (, left), and progesterone receptor (1:200, 16, Novocastra). Tumor cells also displayed focally membranous positivity for epithelial membrane antigen (1:100, E29, Dako) (, right). However, they were negative for glial fibrillary acidic protein (prediluted, Dako), S-100 protein (polyclonal, 1:600, Dako), smooth muscle actin (1:100, 1A4, Dako), synaptophysin (prediluted, DAK-SYNAP, Dako), chromogranin (1:100, DAK-A3, Dako), CD34 (1:100, QBEnd10, Dako), L1 cell adhesion molecule (1:200, polyclonal, Abcam, Cambridge, UK), OLIG2 (EP112; 1:500, Cell Marque, Rocklin, CA, USA), and STAT6 (S-20, sc-621, 1:150, Santa Cruz Biotechnology, Santa Cruz, CA, USA). The Ki-67 (MIB-1, 1:100, Dako) proliferation index was 3%. Intervening sclerosis stained with periodic acid-Schiff and Masson-trichrome.
Based on the above histology, notably, the clear cell morphology containing one mitosis, meningothelial whorls, and the lack of hypercellularity, macronuclei, small cell formation, or brain invasion, the tumor was determined to be an intraosseous meningioma of the microcystic and meningotheliomatous type (World Health Organization grade I). We diagnosed this case as intraosseous meningioma with dural involvement because the tumor was largely located within the sphenoid bone.
At 5 months of follow-up, the patient was healthy, asymptomatic, and scheduled for annual postoperative follow-ups.


A 26-month-old male was airlifted to our hospital after ingesting a mothball. Manual
removal of the mothball at home was unsuccessful. He soon exhibited respiratory
distress, coughing, foamy sputum, drooling, and vomiting. He was taken to the local
emergency center and subsequently airlifted to the local children’s hospital. During
transport, he had hypoxia requiring 10 L on nonrebreather mask. If the oxygen was
removed, his pulse oximetry immediately dropped to 83% on room air. He was pale,
lethargic, and responsive only to painful stimuli. A chest radiograph showed a
foreign body in the esophageal inlet with compressive effects on the trachea.
Initial arterial blood gas showed pH of 7.34, CO2 of 43, O2 of
105, and bicarbonate of 22.8.
The patient was intubated and underwent emergent endoscopy, during which the mothball
was identified in the upper esophagus and was exerting a compressive effect on the
trachea ( and
()). Several
unsuccessful attempts were made (using a Roth Net® retrieval device
endoscopically (STERIS Healthcare, Mentor, OH); using a Parsons laryngoscope and a
4 × 30 rigid esophagoscope and peanut forceps/alligator forceps; using a Boston
Scientific CRETM Pro Wire Guided Esophageal Balloon dilation catheter
inflated to 10-French and introduced over the rigid esophagoscope distal to the
foreign body and pulled back; and using a Rosen needle and tonsil clamps). Removal
was difficult because the foreign body was too slippery, and the esophageal tissue
was tightly adhered to the mothball. Ultimately, successful removal was accomplished
using a straight Miller blade to locate the mothball and removal with a curved Allis
clamp. Post removal, endoscopic esophageal exploration with an OlympusTM
GIF-160 endoscope demonstrated minimal mucosal erosions and no perforations (). A nasogastric
tube was placed at the completion of the procedure.
The patient was admitted to the pediatric intensive care unit (PICU) and remained
intubated for 24 h due to concern for airway cricopharyngeal edema. He was given a
3-day course of dexamethasone, kept nil-per-os (NPO) for 24 h after the procedure,
and put on famotidine intravenously. He was extubated to room air. Esophagram was
normal without any signs of perforation or strictures. Clear liquid diet was started
the next day and advanced to a regular diet. The rest of the hospital course was
unremarkable, and he was sent home. The mothball was sent to pathology for
evaluation and was found be an ovoid firm, tan-white object measuring 1.7 cm in
diameter and composed of paradichlorobenzene.
Two weeks following hospital discharge, he returned to clinic due to solid food
dysphagia. Repeat endoscopy identified a stricture in the proximal esophagus at the
location where the mothball had come into contact with the mucosa (). The stricture
was serially balloon dilatated (), and triamcinolone was injected into the four quadrants of
the stricture area. At a follow-up appointment, he had improved and able to tolerate
solid foods. A third endoscopy showed resolution of the stricture ().


Here, we report a 60-year-old Chinese woman, presenting to a local hospital due to hematuria and diagnosed with left upper tract UC in March 2018. She had a left laparoscopic radical nephroureterectomy in the same month. Postoperative pathological examination confirmed invasive high-grade UC. Immunohistochemistry showed GATA-3 (+), CKH (+), CK7 (+), CK20 (–), P63 (+), CgA (–), Syn (–), CKL (weak +), β-Catenin (+), Ki-67 (+, 25%), CK18 (+), and P40 (+). She was discharged and recovered well after surgery, and had gemcitabine and cisplatin (GC) combined chemotherapy for four cycles. In November 2019, the patient came to hospital with left back and abdominal pain. Computed tomography (CT) examination showed a slightly high-density soft tissue mass shadow of 3.2 × 3.1 cm on the posterior wall of the left abdomen, a dense soft tissue mass shadow on the left internal iliac lymph nodes (3.2 × 4.2 cm, thick-walled annular enhancement in contrast-enhanced CT), and multiple enlarged lymph nodes to the left of the abdominal aorta (maximum diameter of about 1.5 cm) ( before therapy). All masses and enlarged lymph nodes were highly suspected to be metastatic lesions. The patient’s left back pain later worsened, accompanied by a loss of appetite, and a “goose egg” size mass was found at the left waist ( before therapy). In order to identify potential targets for systematic treatment, blood samples were collected from the patient, and the germline DNA was tested with a next-generation sequencing (NGS)-based 605-gene panel and the status of 58 hereditary cancer related genes were reported (), and the somatic circulating tumor DNA (ctDNA) was tested with the same NGS-based 605-gene panel (). The test results suggested that the patient carried a novel germline BRCA2 nonsense mutation p.L557* (c.1670T>A), as well as somatic INDEL mutations, including BRCA1 p.Y1845Pfs*34 (c.5533_6634del), RB1 p.E554Gfs*6 (c.1661_1695del), JAK2 p.M84Vfs*6 (c.250_251.del), and somatic SNV mutations in TP53, KMT2D, MET, ROS1 and IL7R (). Among them, the germline BRCA2 c.1670T>A mutation was discovered for the first time (list of all germline mutations for this patient is provided in ). Based on the above test results, the patient started taking Olaparib orally (300 mg/tablet, bid, po). At 3 months after the initiation of Olaparib therapy, CT reexamination revealed a reduction of the left lumbar mass ( after therapy) and a reduction of the abnormal enhanced mass in the original left kidney area ( after therapy). Multiple enlarged lymph nodes to the left of the abdominal aorta became smaller or disappeared. The overall response achieved partial response (PR). The repeated ctDNA test after 3 months of treatment showed reduction in mutation allele frequency in BRCA1 (from 13.42% to 0.25%), TP53 (from 12.26% to 0.54%), and KMT2D (from 10.21% to 0.21%). The remaining somatic mutations were not detected in the second test (). The tumor mutational burden (TMB) decreased from 6.11 Muts/Mb to 0.76 Muts/Mb. These observations suggested that Olaparib treatment successfully controlled the tumor development and reduced the tumor burden. At the time of submission of this article, the patient has been receiving Olaparib treatment for more than 4 months with continued response.


An 8-year-old Indian girl born out of a nonconsanguineous marriage presented to our outpatient department with chief complaints of light-colored scalp and body hair along with light-colored spots distributed all over the body surface. On examination, she had silvery grey hair over the scalp (predominantly over the frontal and temporal region) and the eyebrows and eyelashes []. Several discrete hypopigmented macules on a background of diffuse hyperpigmentation were present all over the body surface covered with fine grey hair []. The hypopigmented macules were remarkably predominant over the face, trunk, and the lower limbs. The rest of the physical and systemic examination was within normal limits and no other family member was involved. There was no history of any recurrent infections or failure to thrive.
A trichogram revealed coarse unevenly distributed clumps of melanin pigment in the medulla of the hair shaft []. Skin biopsy from the hypopigmented macule revealed enlarged hyperpigmented melanocytes with sparsely pigmented adjacent keratinocytes in the basal layer of the epidermis []. Immunohistochemistry with HMB-45 showed an enlarged and increased number of pigment laden melanocytes []. Masson Fontana stain from the hyperpigmented lesion showed uniform prominence of enlarged hyperpigmented melanocytes [] and from the hypopigmented lesion showed patchy prominence of enlarged hyperpigmented melanocytes []. The hematological and neurological evaluation was done from the respective departments and was normal. Further, the patient was also referred to the department of pediatrics for the assessment for any developmental/growth delay and was found normal. On the basis of clinical examination, absence of neurological or immunological abnormalities, typical findings on hair trichogram and skin biopsy, a diagnosis of GS3 was made. Mutational analysis for confirmation could not be done as it was not available in our center and the patient could not afford it elsewhere.


A 62-year-old male from Bihar presented with multiple nodules on face and extremities of 5 years duration. The lesions first appeared over face and lower limbs and then, gradually spread to the whole body. New lesions kept on appearing, whereas older lesions gradually increased in size. Lesions on right hand and scrotum got ulcerated spontaneously and healed slowly over the next couple of months. There was no history of sensory loss over lesions or extremities, joint pain, weight loss, or systemic symptoms. There was no history of prolonged fever associated with hepatosplenomegaly suggestive of kala-azar. On examination, multiple nontender, dusky erythematous papules, plaques, and nodules of various sizes were noted on the face and extremities [Figure -]. No sensory loss over lesions or extremities was demonstrable and peripheral nerve trunks were not thickened. Routine blood investigations, lipid profile, uric acid, rheumatoid factor, serology for human immunodeficiency virus (HIV), and X-ray of hands and feet were unremarkable.


A 40-year-old male from Bihar presented with multiple nodules around joints of extremities of 2 years duration and erythematous skin infiltration of face, trunk, and upper extremities of 1 year duration. Lesions first appeared over limbs and then, gradually spread to the whole body. New lesions kept on appearing, whereas older lesions gradually increased in size. However, none of the lesions ulcerated. There was no history of sensory loss over lesions or extremities, joint pain, weight loss, or systemic symptoms. There was no history of prolonged fever associated with hepatosplenomegaly suggestive of kala-azar. On examination, multiple nontender, juicy erythematous papules, plaques, and nodules of various sizes were noted on extremities, especially around joints [Figure and ]. In addition, multiple hypopigmented macules and patches were noted on the trunk and upper extremities. Face including ear lobule was remarkable for diffuse erythematous infiltration. No sensory loss over lesions or extremities was demonstrable and peripheral nerve trunks were not thickened. Routine blood investigations, lipid profile, uric acid, rheumatoid factor, serology for HIV, and X-ray of foot were unremarkable. Slit skin smear from ear showed numerous Leishmania donovani (LD) bodies. Serology (rk39) was done and found to be positive.
In both the cases, histopathology showed atrophic epidermis, grenz zone, and curvilinear collection of macrophages, plasma cells, and some lymphocytes in upper dermis along with numerous LD bodies [Figure -]. Fite–Faraco stain did not show any acid-fast bacilli. Considering clinical and histopathological presentation, diagnosis of PKDL (nodular variant) was made. One patient was referred to government healthcare facility to receive amphotericin B under National Vector Borne Disease Control Programme (NVBCP), whereas the other patient was started on amphotericin B and he absconded after 2 injections.
PKDL was first described by Brahmachari in 1922. It usually occurs 6 months to 5 years after the treatment of visceral leishmaniasis, predominantly in the Indian subcontinent and Africa. In 15-20% of cases (consistent with our patients), there is no definite history of kala-azar but these patients hail from the endemic region in almost all the cases.[]
Nodular lesions show a dense, diffuse dermal infiltrate of plenty of histiocytes and plasma cells. The infiltrate is characterized by a sharp margin, a feature which distinguishes the entity from lepromatous leprosy. Rarely, one may find diffuse infiltrate of foamy macrophages, mimicking leprosy. However, the presence of huge numbers of LD bodies provides a clincher for the diagnosis of PKDL.[] Other histological findings include perineural infiltrates,[] sclerosis around the dermal vessel walls.[] Singh et al. had also reported the presence of atrophic epidermis and dermal adnexae being trapped in the dense infiltrate.[]
Clinical differentials for nodular PKDL include lepromatous and histoid leprosy, tuberous xanthoma, xanthoma disseminatum, cutaneous T cell lymphoma, etc. Besides, histological differentials for nodular PKDL include lymphocytomas, Jessner's lymphocytic infiltrate, pseudolymphoma, nodular lepromatous leprosy, histoplasmosis, etc.[]
Therapeutic response is not satisfactory despite the availability of a wide number of drugs including pentavalent antimonials, amphotericin B, miltefosine, immunotherapy with Bacillus Calmette–Guérin (BCG) and heat-dead Leishmania amazonensis promastigotes. Combination therapy with liposomal amphotericin and miltefosine has been successful in a few cases. Poor cellular immunity makes this condition very difficult to treat and it is the sole cause responsible for the high rate of relapses in the course of the disease.
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Nil.
There are no conflicts of interest.


A 70-year-old man with a smoking history of 50 pack-years had a small nodule in the right lung field on chest X-ray during an annual health check-up (Fig. ). HRCT demonstrated a PSN in the peripheral area of segment 10 of the right lung (Fig. ). The total area of the PSN measured 25 × 20 mm and the solid area 21 × 20 mm. There was no distant metastasis or lymphadenopathy. In routine preoperative laboratory tests, carcinoembryonic antigen (2.2 ng/mL) and cytokeratin-19 fragment (1.2 ng/mL) were within normal ranges. After clinical diagnosis of well-differentiated AC of the right lung, stage IA3-cT1cN0M0 (Union for International Cancer Control TNM classification, version 8), we successfully performed right lower lobectomy and mediastinal lymph node dissection via video-assisted thoracic surgery.
The tumour was pathologically diagnosed as SCC with lepidic proliferation. Macroscopic and representative histopathological findings of the tumour are represented in Figure . We compared the HRCT image (Fig. ) and macroscopic and loupe-level findings of the resected tumour (Fig. ). The solid and GGO areas of the PSN on HRCT corresponded to central and peripheral areas of the tumour, respectively. Histopathological examination of the central area of the tumour indicated the typical finding of invasive SCC with keratinization (Fig. ). In the peripheral area of the tumour, we detected a lepidic growth pattern represented by carcinoma cells between non-neoplastic type II pneumocytes and the alveolar basement membrane (Fig. ). Tumour-infiltrating lymphocytes were scanty in whole tumour tissue. On immunohistochemical staining, tumour cells had squamous cell differentiation shown by positivity of p40 (Fig. ) and negativity of thyroid transcription factor 1 (TTF-1). There was no difference of p40 positive rate of carcinoma cells between central and peripheral lepidic lesions. A monolayer of reactive type II pneumocytes was highlighted by TTF-1 positivity, and was covered by lepidic spreading of carcinoma cells (Fig. ). Ki-67 index in central solid and in peripheral lepidic lesions was about 40% and 10%, respectively.


In January 2014, a 42-year-old never-smoker woman who had been complaining of a dry cough for 2 months was diagnosed with a 2-cm-large lesion of the medium lobe of the lung. Biopsy of this lesion obtained during bronchoscopy was compatible with TTF1-positive adenocarcinoma. A PET/CT scan was positive for the presence of multiple metastatic ipsilateral mediastinal lymph nodes and a single metastasis in the contralateral lung, which configured T2N2M1–stage IV disease. As molecular biology was negative for EGFR mutation and ALK gene rearrangement, the patient started first-line chemotherapy with cisplatin/pemetrexed, of which she received four cycles with partial response followed by pemetrexed maintenance. In August 2014, disease progression in the right lung was observed at a PET/CT scan, and the patient received stereotactic radiotherapy on the primary lung lesion (62 Gy, 25 fractions). After radiotherapy to the lung, systemic therapy was halted and the patient was followed up with serial PET/CT scans every 3 months until May 2015, when a new PET/CT scan showed progressive disease in the left lung. A new 1-cm-large lesion in the left occipital region of the brain with no neurological symptoms was also detected at a brain MRI. At that time, since the patient was a young never-smoker woman who was negative for both EGFR and ALK, we carried out sequential molecular testing for select genetic drivers including HER2. Direct sequencing of the HER2 gene revealed the presence of a G776VinsC mutation (Fig. ). This mutation configured a disease potentially responding to anti-HER2 therapies, so the patient was managed thereafter with multiple lines of anti-HER2 therapies (see Fig. for a timeline of significant events). After receiving stereotactic radiotherapy (20 Gy, single fraction) to the new brain lesion, the patient resumed pemetrexed in combination with the anti-HER2 monoclonal antibody trastuzumab given at 8 mg/kg loading dose followed by 6 mg/kg, both drugs being administered every 3 weeks. The choice of resuming pemetrexed was based on the fact that we aimed to further exploit a histologic-specific cytotoxic agent active in lung adenocarcinoma. In October 2015, a PET/CT scan was compatible with complete extracranial response, while an MRI showed disease stability of the brain lesion. The patient continued pemetrexed plus trastuzumab until February 2016 when a new PET/CT scan showed extracranial disease progression in both lungs. As a result, it was decided to continue tri-weekly trastuzumab and change the companion cytotoxic drug by switching to weekly paclitaxel. Importantly, a new PET/CT scan performed on June 2016 showed partial response at extracranial sites of disease that lasted for approximately 1 year until May 2017, when a PET/TC scan showed disease progression in both lungs. At that time, the patient had to withdraw from anti-tumour treatment because of the development of severe mitral insufficiency secondary to bacterial endocarditis, which was managed surgically with mitral valve repair. At recovery, a new restaging through a PET/TC scan on May 2018 showed further disease progression in the lung, with a new MRI showing stable disease in the brain. As the mitral insufficiency was not deemed to be trastuzumab-related, after careful discussion with the patient, a decision was made to resume tri-weekly trastuzumab with a change in the companion cytotoxic with the introduction of oral vinorelbine on days 1 and 8 every 3 weeks. A new PET/CT scan performed after 4 months showed stable disease at extracranial sites. In January 2019, a PET/CT scan revealed disease progression in the lung, while an MRI documented disease progression in the brain with the onset of a new centimetric lesion in the right cerebellum. In April 2019, following radiosurgery to the new brain lesion (20 Gy, single fraction), the patient started treatment with the pan-HER-TKI poziotinib at the dose of 16 mg daily p.o. within an expanded access program, from which she obtained a partial response in the lung. In October 2019, the disease progressed again in the lung and brain with the onset of multiple brain lesions. The patient then received whole brain radiotherapy (30 Gy, 10 fractions) and started chemotherapy with carboplatin/gemcitabine, which is still ongoing as of January 2020. Written informed consent to publish the patient’s case was provided by the patient in an anonymous form.


Case 1 is a 32-year-old woman originating from Yunfu City in Guangdong Province, China. She was referred to our hospital for a routine prenatal examination at the 18th week of gestation and then underwent thalassemia screening. Case 2 is a 51-year-old man from Guangzhou City in Guangdong Province. He attended our hospital for routine partner testing for thalassemia. These two cases were from unrelated families. Both agreed to participate in our study and signed informed consent forms. All studies were approved by the Ethics Committee of Guangdong Women and Children Hospital.
Blood samples were collected and hematological parameters were determined using a Sysmex XN5000 automated hematology analyzer (Sysmex Corporation, Kobe, Japan). Hb analysis was conducted with an automated capillary 2 electrophoresis system (Sebia, Lisses, France). Genomic DNA was extracted from peripheral blood leukocytes using the Lab-Aid 820 automation system (Zee San Biotech Company, Fujian, China). Twenty-three mutations common in individuals from southern China were routinely measured in our laboratory by a suspension array system, as previously described. α1-, α2-, and β-globin genes were independently amplified by PCR using previously described primer pairs, then PCR products were purified and sequenced by Sangon Biotech Co., Ltd. (Shanghai, China). The sequences were compared with National Centre for Biotechnology Information reference sequences (HBA1: NC_000016.10: 176680-177522; HBA2: NC_000016.10: 172876-173710; HBB: NC_000011.10: 5225464-5227071) using Sequence Scanner software (Applied Biosystems).
Hematological indices and genotypes are summarized in . Both samples showed characteristics of microcytic and hypochromic erythrocytes. Iron deficiency was excluded (data not shown). In both cases, capillary electrophoresis (CE) revealed an abnormal Hb X fraction which was close to the Hb A peak and easily identified, even if partial overlap persisted (). The suspension array system determined that both cases carried heterozygous (- - SEA/) deletions for α-thalassemia and were negative for β-thalassemia (data not shown). DNA sequencing detected a substitution (HBA1: c.343C>G) at codon 114 of HBA1 that was previously reported as Hb Broomhill (), which was consistent with CE results. No other mutation with clinical significance was observed in either of the cases. Eventually, the two patients were diagnosed with compound heterozygosity for Hb Broomhill and the (- - SEA/) α-thalassemia deletion.


A 64-year-old male underwent endoscopic mucosal resection (EMR) for a sessile type lesion (0-Is) in the rectum 2 years before presentation. The histological diagnosis was adenocarcinoma invading into the muscularis mucosae. The tumor was close to the vertical stump, and there were some areas where it was difficult to determine the stump due to the influence of cauterization. Adjuvant chemotherapy was not applied because it was determined the pathological curative resection had been performed. Upon presentation to the clinic, he was diagnosed with a submucosal lesion on the EMR scar from the rectum to anal canal on the anal transition zone. Histopathological examination suggested a local recurrence of rectal adenocarcinoma. He was referred to our hospital for definitive diagnosis and treatment a month after the endoscopic biopsy. FDG-positron emission tomography/computed tomography (CT) showed 2-fluoro-2-deoxy-D-glucose (FDG) accumulation of pelvic lymph nodes (maximum standardized uptake value [SUVmax] 4.7) but not in the rectum.
Two months after the endoscopic biopsy, an endoscopic submucosal dissection (ESD) for diagnostic purposes was performed for the local recurrent lesion. Histopathological examination revealed tumor cells with round atypical nuclei and eosinophilic cytoplasm and signet cells in the epithelium. Synaptophysin was diffusely positive in tumor cells of both histological types, and chromogranin A was focally positive by immunohistochemistry. This indicated the tumor had both exocrine and endocrine features in the same cell. The final diagnosis was rectal AmC.
A month later, endoscopic ultrasound of pelvic lymph nodes and a colonoscopy were performed. Pelvic lymph nodes accumulated FDG could not be detected, but the local recurrence of AmC on the ESD scar was shown. A month later, an abdominoperineal resection including dissection of lymph nodes was performed, resulting in R0 resection. Findings of the histopathological examination of surgically resected specimens were similar to those of the previous endoscopic biopsy. CDX-2 and synaptophysin were diffusely positive, chromogranin A and MUC2 were focally positive and MUC5AC and MUC6 were negative (). The recurrent rectal AmC was partially exposed to the surface layer and invaded into veins and lymphatic vessels. Tumor cells were also found in pelvic lymph nodes. Comprehensive genetic testing showed mutation of KRAS codon 61 Q61R, CCND1 amplification, FGF19 amplification and FGF3 amplification.
A month after surgical resection, CT showed liver metastases (). FOLFOXIRI was chosen as first-line palliative chemotherapy. Heterozygosity for the UGT1A1*28 allele was recognized. The regimen of FOLFOXIRI was folinic acid [L-LV; 200 mg/m2, on day 1] + irinotecan [CPT-11; 150 mg/m2, on day 1] + oxaliplatin [L-OHP; 85 mg/m2, on day 1] + fluorouracil [5-FU; 2400 mg/m2, continuous infusion for 46 h]. Compared with the original FOLFOXIRI regimen, CPT-11 and 5-FU were reduced due to concerns of adverse side effects. The best overall response (BOR) was partial response (PR) (−37.5%) after six cycles of FOLFOXIRI (). After six cycles of FOLFOXIRI, the treatment regimen was changed to FOLFIRI due to peripheral neuropathy. After 12 cycles of FOLFIRI, the disease progressed. The progression-free survival (PFS) was 8.7 months. After progression, FOLFOX plus bevacizumab (Bmab) was administered. The BOR was stable disease (+6.5%) after four cycles of FOLFOX plus Bmab. After eight cycles of FOLFOX plus Bmab, disease progression was confirmed, resulting in PFS of 4.4 months. He died due to the primary disease 16.0 months after the induction of FOLFOXIRI.