On February 2017, a 36-year-old male presented weight loss, low-grade fever and sweating. A CT scan revealed a voluminous enlargement of all lymph nodes (left LC, axillary and inguinal lymph nodes, with a maximum diameter of 5 cm, and right LC with a 9 cm diameter), with bilateral pulmonary micronodules; in the spleen was 3 cm and in the liver 2 cm, without parenchymal lesions. All lesions were PET scan-positive, and the patient was diagnosed with stage IVB cNS HL, type 2 BNLI. In March 2017, the patient started a treatment with the ABVD regimen; during the second cycle, despite a reduction of superficial nodes (diameter 3 cm), a fast progression of the disease was observed, with discomfort and enlargement of LC nodes (7 cm). Therefore, the treatment was switched to BEACOPP escalated for 3 cycles, with stem cell mobilization. After an initial significant node reduction, during the third cycle a new enlargement was observed, with a PET scan result of partial response (PR). In July 2017, the patient started 3 cycles of BeGV, and in October the PET scan was negative. HLA investigation identified a matched sibling donor. During pre-transplantation exams, a biopsy of the right LC node revealed a new progression. A treatment with 2 cycles of brentuximab was started, with PR. After the addition of bendamustine for 2 additional cycles, PET and abdomen ultrasound scans resulted negative. In May, the patient underwent autotransplantation with complete remission (CR), but he presented a symptomatic relapse after 2 months, with PET scan positive for nodes, bones, spleen and liver. CT and NMR scans revealed a diffuse positivity for nodes (max 3 cm), spleen hypodense lesions (max 2.6 cm), focal liver lesions (max 1.6 cm), and intertrochanteric femoral lesion (2 cm). In September, a new PET scan revealed a further increase of dimension and metabolic activity of part of the abdominal nodes, with new vertebral lesions (D9, D10, L2, L4), and with a slight regression of other sites. Four cycles of brentuximab were scheduled, with a concomitant administration of low dose corticosteroid. In December 2018, a treatment with nivolumab was started, with a good clinical response and symptoms regression, and the corticosteroid administration was discontinued. After 4 cycles of nivolumab, a DP (affecting spleen, liver, bones, and mediastinal, abdominal, LC and axillary nodes) was revealed by PET scan and confirmed by NMR.
Nivolumab therapy is currently ongoing. A hepatic bi- opsy was scheduled but not performed as no lesions were identified with ultrasound scan. The patient is currently free from systemic symptoms. A PET scan re-evaluation is scheduled, and a HLA identical donor is currently available.
Before the development of BV and CPI, the median survival of HL patients relapsing after ASCT was 25 months (). Allo -SCT could potentially cure about 40% of these patients, particularly when performed in the setting of a chemosensitive disease ().
In patients relapsed after ASCT, BV demonstrated an Overall Response Rate (ORR) of 74% with 34% of cases with a CR; estimated PFS and Overall Survival (OS) were 9.3 and 40.5 months, respectively, with longer survivals in CR patients (). Moreover, Chen et al. showed that BV- treated patients had a better 2-year PFS after allo-SCT compared to patients re-induced with standard chemotherapy (59.3% vs. 26.1%), with reduced cumulative incidence of relapse or progression (23.8% vs. 5.65%) due to better disease control prior to allo-SCT ().
BV could be considered the most suitable drug to “bridge” the patients to allo-SCT. However, 38% of complete BV responders could maintain a sustained response over time, also without allo-SCT consolidation (). For this reason, a delay of allo-SCT to the time of DP during or after the BV treatment is now considered reasonable, provided that a salvage treatment with a CPI (nivolumab and pembrolizumab) is available. In this setting, pembrolizumab demonstrated an ORR of 73.9%, with 21.7% CR (), and nivolumab an ORR of 68%, with 13% CR ().
Nevertheless, only a minority of CPI-responding patients obtain a long-term remission, and allo-SCT remains the only potentially curative therapy. However, its timing in patients treated with CPI is matter of debate. Patients undergoing allo-SCT after CPI appeared at increased risk of grade 4 acute graft versus host disease (GVHD), veno-occlusive disease (VOD), and noninfectious febrile syndrome, requiring a prolonged steroid treatment. It should be underlined that the relapse rate was lower than previously reported (16% at 1 year), with an encouraging 1 year PFS of 74% (). Recently, a large pooled analysis suggested that allo-SCT after CPI is feasible and not associated with higher mortality, provided that a careful consideration is given to prevention, early detection and treatment of GVHD (). As questioned by Broccoli and Zinzani in a recent review, should allo-SCT be performed only in patients achieving a CR, in all patients with at least stable disease, or only in patients progressing while on CPI? (). Herbaux and colleagues suggest keeping CR and PR patients on therapy instead of stopping it to proceed to allo-SCT (). This is motivated, on one hand, by the relative safety of CPI compared to allo-SCT and, on the other, by the possibility to reinduce remission after CPI failure. In a retrospective analysis, salvage chemotherapy following CPI resulted in an ORR of 53% (,). Nevertheless, the authors recommend referral to a transplantation center for a potential transplantation at the time of CPI failure, considering an early allo-SCT only for patients in remission, with heavily pretreated refractory disease and no viable post–CPI salvage options. Shah and Moskowitz proposed an algorithm () where the patients achieving CR continue the CPI therapy for 3 additional months: if the CR is maintained, the authors suggest to stop the therapy and restart only in case of progression. For PR patients, the authors continue the therapy due to a possible late conversion to CR, but consider allo-SCT sooner. Finally, if there is stable disease on CPI treatment, the authors suggest to continue the therapy until DP, followed by an alkylator-based therapy or a clinical trial as a bridge to allo-SCT in case of responding disease. If allo-SCT is scheduled, CPI treatment should be hold for 6 weeks before transplantation. A reduced intensity conditioning, a bone marrow source and a post-transplantation cyclophosphamide treatment should be considered to minimize the risk of GVHD and VOD (). Interestingly, these algorithms take into account the response to CPI treatment as outlined by PET/CT scans. However, CPI-induced activation of antitumor immune cells could theoretically increase the 18F-FDG uptake, masking the CPI efficacy. This so-called pseudoprogression, with imaging findings suggestive of progression, followed by later response, has been described in solid tumors and confirmed in HL patients. In 2016, the LYmphoma Re- sponse to Immunomodulatory therapy Criteria (LYR-IC) introduced the concept of indeterminate response to indicate the time interval until a biopsy or subsequent imaging confirm either a pseudoprogression or a true progression (). On the other hand, hyperprogression, a condition in which CPI initiation leads to a paradoxal increase in tumor growth rate, seems to be associated with a worse prognosis (). The literature data reported above led us to continue the CPI treatment in our patient, due to a satisfactory clinical response despite the progression at first PET/CT scan re-evaluation, but also to schedule allo-SCT despite the subsequent response, in consideration of the high probability of relapse and of the lack of suitable salvage therapy.


In 2012, a 49-year-old male patient with Parkinson’s disease in his past medical history, was diagnosed with stage IIIB cHL, and with International Prognostic Score of 4. He received 5 therapy lines: 6 cycles of ABVD regimen, resulting in a PR, 4 cycles of IGEV regimen followed by ASCT, with PR, 4 cycles of BV, resulting in DP, and then 6 cycles of bendamustine, with no response, showing a chemorefractory disease. Therefore, in 2014 we performed an allo-SCT from a matched sibling donor, due to the lack of other treatment options. The patient achieved a PR, that lasted for 28 months after allo-SCT. Subsequently, DP required additional treatments. The patient started a treatment with the anti-PD-1 nivolumab, at the standard dose of 3 mg/kg every 2 weeks. After 3 cycles, the patient developed a grade 2 elevation of liver enzymes and a grade 2 cutaneous and ocular GVHD. The nivolumab treatment was discontinued and corticosteroid treatment started, with a consequent normalization of the liver enzymes and the regression of cutaneous and ocular signs after 4 months. At that time, disease revaluation showed a CR.
Allo-SCT is a treatment option for patients with re- lapsed or refractory HL, when a previous autologous transplantation failed. Since the allo-SCT -related mortality continues to decline, with preparative regimens characterized by a lower-intensity and a better supportive care, the treatment of relapsed disease is increasing. Approximately 30% of allografted lymphoma patients relapse after allo-SCT ().
For patients who develop disease recurrence or progression after allo-SCT, the prognosis is unfavorable and the treatment is challenging as most patients are heavily pretreated, and often have a chemotherapy-refractory disease.
Aside from rapidly minimizing the systemic immunosuppression, no standard strategy is currently available.
The scientific basis for the use of CPI in HL is real and strong. In tumor tissue, HL cells are scanty and surrounded by a large number of inflammatory tumor-infiltrating lymphocytes. In particular, Reed-Sternberg cells are characterized by the 9p24 amplification, encoding for both the PD-1-/PD-2-ligands and for the Janus kinase (JAK)-2. The latter activates the JAK/STAT pathway (), leading to a further enhancement of PD ligand expression on Reed-Sternberg cells. Additionally, around 40% of patients with cHL are positive for Epstein-Barr virus, which is associated with high expression of PD-1 and PD-2 ligands ().
Recently, early-phase clinical trials on PD-1–blocking antibodies nivolumab and pembrolizumab showed a substantial therapeutic activity and an acceptable safety profile in patients with relapsed or refractory HL (-).
Of note, both trials excluded patients with a previous history of allo-SCT, because of concerns about GVHD reactivation.
Current strategies for relapsed HL after allo-SCT are discouraging (,). Using different approaches (DLI with or without chemo- therapy, BV, or bendamustine), poor results were reported, with a median PFS ranging from 6 to 18 months.
The immune-mediated graft-versus-tumor (GVT) effect endows the allo-SCT with the potential to cure malignancies refractory to all other treatments. Nevertheless, it is associated with the risk of donor cell-mediated GVHD, which mainly contributes to its relevant morbidity and mortality. In theory, the GVT effect might be enhanced by immune CPI such as ipilimumab (anti-cytotoxic T-lymphocyte-associated protein 4), nivolumab (anti-PD-1) or pembrolizumab (anti-PD-1), by releasing the brakes on GVT conveying tumor-suppressed lymphocytes. Nevertheless, severe GVHD reactions might be unleashed as well.
CPI administration has also been tested for post allo-SCT relapse, and, although the response rates are high, the toxicity is substantial as well. A multicenter retrospective trial of 31 lymphoma patients, 29 with HL, treated either with nivolumab or with pembrolizumab after allo-SCT relapse, found a high ORR of 77%. However, a treatment-related GVHD occurred in 55% of patients and tended to be highly refractory to conventional GVHD management, with a mortality of 26% (). Another retrospective trial on 20 HL patients receiving nivolumab after allo-SCT found an ORR of 95%, with a 30% incidence of GVHD, and 10% of the patients died of GVHD ().
While the preliminary data demonstrated no significantly increased GVHD in patients treated with ipilimumab post allo-SCT, there is still a substantial concern regarding the safety of PD-1 inhibitors in this setting. In fact, increased GVHD-related lethality has been demonstrated in a murine model of acute GVHD when blocking PD-L1 ().
There is a possibility that anti–PD-1 administration during the early phase of transplantation would trigger severe GVHD secondary to decreased PD-1/PD-L1 ligation soon after the allo-SCT ().
Donor source, type of GVHD prophylaxis, history of GVHD, dose and timing of anti–PD-1 therapy, and immunosuppression at time of anti–PD-1 administration should be considered as variables potentially influencing the development of GVHD in clinical trials that evaluate the treatment with checkpoint blockade after allo-SCT.
In phase 1 studies with nivolumab and pembrolizumab for treatment of relapsed and refractory HL, grade 3 hepatic and dermatologic toxicities were observed in 5% of patients, and there were no drug-related grade 4-5 events (-).
One case of fatal hepatic toxicity has been reported in a lung cancer patient after the treatment with an anti-PD-1 monoclonal antibody ().
Nevertheless, early onset of severe and fatal events occurred more frequently than expected when anti–PD-1 monoclonal antibodies were administered post allo-SCT.
There are context-dependent functions of the PD-1/PD-L1 axis in allo-SCT, including timing of pathway activation and organ-specific immunogenicity, donor vs. host expression, and peripheral tolerance, which affect the risk of aGVHD and cGVHD.
However, while reversing the suppression of allogeneic GVT effects with PD-1 inhibition appears particularly appealing, special caution has to be taken in the context of an allogeneic immune system, given the role of the PD-1 axis in the pathophysiology of GVHD as well. In conclusion, CPI are increasingly being used in this setting and appear to be effective, although with conflicting safety results, because their administration can be complicated by the rapid onset of severe and treatment-refractory GVHD.


Last February, a 63-year-old man was admitted to our Emergency Department with a widespread edema of the right forearm and fever (ranging from 37.5 to 38.5 °C) started 2 days before. On clinical examination he was observed to have a 2 x 3 centimeters erythematous lesion, with skin desquamation and a central double puncture wound at the ulnar side of the forearm (). A purulent drainage was found when squeezing the puncture wounds. He complained of severe pain, burning and paresthesia extended to the right hand. He reported to be in good general health, with no history of major diseases. The skin reaction appeared as a consequence of a Scolopendra Subspinipes bite, happened during a trip to Santo Domingo one week before. After the bite he went to the local Emergency due to bleeding at the site of the bite and perilesional itching. Tetanus prophylaxis was administered; in addition, ice packs, Paracetamol (2 g / day) and Prednisone (25 mg / day) were prescribed. However, he stated not to have regularly taken his medicines and to have continued sea baths without any bandage. It was then performed an ultrasound evaluation which brought to a diagnosis of supra-fascial cellulitis of the right forearm. Laboratorary findings showed leukocytosis (white blood cells: 18.7 x 109/L) and C-reactive protein (CRP) increase (223 mg/l). According to infectiologists, it was decided to perform a surgical debridement. Multiple samples of pathological tissue were collected for culture tests. Empirical antibiotic therapy with intravenous Amoxicillin/Clavulanic Acid (2.2 g 3 times a day) was started only after the tissue samples had been taken. Culture tests showed the presence of a microbial superinfection caused by Staphilococcus Aureus (S.Aureus) sensitive to Amoxicillin. The Amoxicillin/Clavulanic Acid intravenous administration was prolonged for 6 days. The therapy was then shifted to oral administration at the dose of 875/125 mg 3 times a day and stopped after 8 additional days, at the complete wound healing and CRP values normalization. Nevertheless, 5 weeks later he came back to our Emergency with a bullous skin lesion at the dorsal side of the right thumb, marked edema of the hand, severe pain and paresthesia of the fingers (). CRP value was 53.9 mg/L, white blood cells were 13 x 109/L. A second surgical debridement was performed. Tissue samples for new culture tests were collected. Dorsal fasciotomy of the thumb and a precautionary dorsal double-fasciotomy of the second and fourth inter-metacarpal spaces were executed. Intravenous antibiotic therapy with Amoxicillin/Clavulanic Acid was restarted and prolonged for 10 days, as the culture tests results showed once again a S.Aureus Amoxicillin-sensitive infection. The patient was proposed to undergo hepatitis C, hepatitis B and HIV antibody tests to exclude a possible immunosuppression; however, he did not give his consent to the aforementioned tests. The second and fourth metacarpal dorsal fasciotomies were sutured 6 days later. The thumb fasciotomy was left to heal via secondary intention and took two months to reach the complete wound healing ().


A 15-year-old male, non-professional soccer player, arrived at the emergency department complaining of pain and swelling in his left elbow.
He reported intense pain following a fall on his elbow during a soccer match; no vascular or nervous impairments were detected.
After the clinical visit an elbow dislocation was suspected; x-rays confirmed this suspicion ().
The patient also underwent to a CT scan, which confirmed the dislocation and also demonstrated the presence of an intra-articular fragment resulting from the avulsion of the medial epicondyle().
The dislocation was therefore reduced in deep sedation, but clinically valgus instability, and intra-articular impingement could be yet appreciated; no vascular or nervous impairments were detected after the reduction.
Radiographs and a CT following sedation showed the success of the reduction and the presence of a big intra-articular fragment ().
The day after the patient had ORIF of the fragment with a cannulated screw and a washer though a medial approach.
The ulnar nerve, which is potentially vulnerable during this approach, was identified, isolated and protected ().
The intra-articular fragment was then identified and reduced in its anatomical position; it was first stabilized with a kirschner wire and definitively synthesized with a cannulated half threaded screw with a washer ( and ).
After 14 days of cast immobilization patient followed an intensive physiotherapy program of 40 days characterized by progressive assisted active and passive kinesis and idrokinesis therapy. The final check 90 days after surgery showed that the operated limb had no deficit in bending with respect to the healthy one.
In extension, there was a deficit of 5 degrees (); no residual pain and no lack of strength was present. The patient was satisfied with the result achieved. X-rays demonstrated consolidation of the fracture ().


A 39-year-old female patient without any medical illness presented with right medial canthal swelling persisting for three months. The swelling was painless but gradually increased in size. She also complained of right epiphora and intermittent nasal blockage. There was no blurred vision, history of epistaxis, facial pain, and hyposmia. She also denied any history of trauma or insect bite to the area.
Inspection of the eye demonstrated a solitary rounded lesion at right medial canthus measuring 2 cm x 2 cm with no overlying skin changes (). The mass caused mild right eye propto-sis. The mass was non-tender but fixed to the underlying structure. Vision was 6/9 for both eyes. Otherwise, paranasal sinus palpation was normal. Rigid nasoendoscopy only revealed right septal deviation without medialization of the lateral wall of the right nasal cavity (). Otherwise, no mass or polyp was seen and the fossa of Rosen-muller were clear.
Computed tomography (CT) scan of orbit and paranasal sinus revealed a well-encapsulated cystic lesion in the right extraconal region measured 2.5 cm x 1.8 cm x 2.3 cm. This lesion caused indentation and convexity of the right lamina pa-pyracea (). The left lamina papyracea was intact. The wall of the lesion was not thickened or inflamed. No fatty component, calcification, ossification within the lesion were seen. The left lamina papyracea and the orbits were intact bilaterally. Both globes and lenses were normal. The nasal septum deviation to the right side with a small septal spur was detected. The radiological diagnosis of orbital dermoid cyst with differential diagnosis from epidermoid cyst was made.
Magnetic resonance imaging (MRI) of paranasal sinuses and orbit revealed an expansile lesion measuring 2.3 cm x 1.5 cm x 2.2 cm. On Fluid Attenuated Inversion Recovery (FLAIR) sequence, the lesion showed hyperintense matrix which caused extrinsic compression of the medial extraconal space of the right orbit appearing as a human with three eyes ().
The mass caused complete dehiscence of the anterior part of the right lamina papyracea, compressing the right medial rectus. The right globe was laterally displaced and caused proptosis. Otherwise, the right globe was preserved. The extraocular muscle, the optic nerve, and intraconal fat were preserved. There was no lesion in the region of the right lacrimal gland. Mucosal thickening and polyp were seen in the right maxillary sinus. Mild mucosal hypertrophy in the left anterior ethmoid sinus was identified by MRI as the right ethmoidal mucocele.
Right endoscopic orbital decompression was performed. Then septoplasty was performed to provide surgical access. We thought that the mucocele was originated from right ethmoidal sinus as demonstrated by MRI. However, intraoperatively a retention cyst at posterior ethmoidal sinus with the convexity of lamina papyracea was seen. Middle meatal antrostomy revealed maxillary sinus mucosa looking healthy without any polyp seen. After removal of lamina papyracea thick yellowish mucin discharge (mucocele) coming from the orbital cavity was seen (). The fluid drained out was about 10 cc with intact periorbital fat. HPE confirmed that the mass was mucocele.
Postoperatively, none of the complications such as blurring of vision, epistaxis or septal hematoma were seen. Postoperative vision test was 6/9 for both eyes. Upon palpation of right eye postoperatively, any palpable cystic lesion over right medial canthus was not detected. She was discharged well with nasal douching and reviewed a week later on. Rigid nasoendoscopy that was repeated one month after surgery revealed minimal blood clots and absence of synechiae.


A 55-year-old male presented to the emergency department in April 2020, with the complaints of sudden-onset, left-anterior chest pain that started 4 h before presentation. Pain was 5 out of 10 in intensity, with radiation to the left arm, and no associated shortness of breath (SOB). He also reported a 2-week history of dry cough and fever. Patient is a police officer, and two of his coworkers tested positive for SARS-CoV-2 infection. Past medical history significant for hypertension, hyperlipidemia, coronary artery disease (CAD) status post-percutaneous coronary intervention (PCI) with drug-eluting stent (DES) in 2005 and coronary artery bypass graft × 4 in 2008, untreated type II diabetes mellitus and polycythemia. Differential diagnosis included acute coronary syndrome, acute pulmonary embolism, pneumonia due to corona virus disease-2019 (COVID-19), acute on chronic heart failure exacerbation, myocarditis, pericarditis, tension pneumothorax and costochondritis.
Chest X-ray (CXR) on admission showed severe diffuse bilateral pulmonary infiltrates with air bronchograms (), which was concerning for COVID-19 pneumonia. Electrocardiogram (ECG) showed acute inferolateral ST-segment elevation myocardial infarction (STEMI). ST-segment depression in V1 and V2 suggested posterior myocardial injury (). Initial cardiac troponin I (TnI) was 0.02 ng/L (reference range < 19 ng/L) at 7 h. Reverse transcription–polymerase chain reaction was positive for SARS-CoV-2.
On physical examination, he was diaphoretic, heart rate 100 beats/minute (bpm), elevated blood pressure at 148/100 mm hg and hypoxic on room air. Repeat TnI was elevated at 19 ng/L at 11:40 h. STEMI protocol was activated and patient was taken to the cardiac catheterization lab. Left heart catheterization with coronary angiography and graft injection showed 90% stenosis of both proximal and mid-portion of the RCA with a TIMI flow of 3. Saphenous vein grafts to mid-diagonal artery and mid-obtuse marginal artery were patent. Left ventricular ejection fraction was 55%. Successful PCI of the proximal and mid-RCA using the balloon angioplasty and DES was performed. Post-PCI stenosis was 0% with TIMI flow of 3 (). Severe hypoxia out of proportion to the CAD was noted during the procedure. ECG post-PCI showed near normalization of the ST-segment elevation (). He was given prasugrel and started on eptifibatide drip and was transferred to the medical intensive care unit. Even though his chest pain improved following the PCI, he was still complaining of SOB requiring up to 10 L of oxygen by high-flow nasal cannula (HFNC). Because of the rapid and abrupt decompensation, he was intubated on the hospital day 1 (HD#1). Five-day course of azithromycin and hydroxychloroquine was completed with no significant improvement. Patient received two doses of intravenous tocilizumab on HD#5 and #6. Refractory hypoxemia (arterial blood gases: pH 7.41, pCO2 53.4, pO2 72.4, HCO3 34) persisted despite maximal ventilator settings (proned, FiO2 100%, PEEP 15 cm H2O, epoprostenol sodium and paralytics). Therefore, given his young age and otherwise healthy status, it was decided to place him on venovenous (VV) ECMO support. He was cannulated at the bedside with 25 French inferior vena cava cannula and 25 French right internal jugular cannula. Flow of 6 L/minute was provided with FiO2 of 100% and sweep of 8. Ventilator mode was set to pressure-regulated volume control, very low tidal volume at 300 mL, 15 breaths/min, minute volume 4.5 L/min, PEEP 12 cm H2O, FiO2 60%. On HD#9, interleukin 6 (IL-6) level was 86.9 pg/ml (a 12-fold decrease), and ECMO was decannulated on the HD#13. He was extubated on the HD#16 and was breathing on 10 L oxygen by HFNC. He remained only on dexmedetomidine, was awake and followed commands. On HD#17, oxygen weaned to 4 L, and on HD#18, he was off of oxygen and breathing on room air. He was discharged to home on HD#24. Inflammatory markers trended down () and the IL-6 level remained low at 141 pg/ml. CXR improved significantly on discharge when compared to that of admission (). He is doing well without any residual symptoms as we write this report.


We report the case of a 76-year-old male with advanced HF due to non-ischaemic dilated cardiomyopathy with ventricular dysfunction since 1998 (Videos 1 and 2) .
His family history includes HF and sudden cardiac death in his maternal grandmother, and in his mother and brother at an early age (45 and 60 years, respectively). Four healthy sons with normal clinical studies [electrocardiogram (ECG) and echocardiogram]. In genetic study requested, no pathogenic variants were found (dilated cardiomyopathy panel with 121 genes using the latest generation sequencing technique).
As personal background point out former long-term smoker, arterial hypertension, dyslipidaemia, chronic obstructive pulmonary disease, and chronic kidney disease.
Physical examination revealed mild signs of pulmonary congestion and peripheral oedema. The LVEF was severely depressed (<20%) with no changes despite therapeutic optimization.
Implant of implantable cardioverter-defibrillator (ICD) in 2005, with later optimization to ICD-CRT and with atrioventricular node ablation due to multiple episodes of atrial fibrillation (AF), with unsuccessful cardioversions and causing a low percentage of biventricular pacing.
In optimized medical treatment with Bisoprolol 5 mg/8 h, Eplerenone 25 mg/24 h, and Sacubitril/Valsartan 24/26 mg/12 h (maximum doses tolerated due to blood pressure and renal dysfunction) and in treatment with Levosimendan ambulatory infusions every 4 weeks since January 2018.
The patient presented four admissions for arrhythmic storm since 2016, the last one in October 2018, with ablation of the extrasystolic focus in the left ventricular outflow tract, without achieving the disappearance of arrhythmic episodes, continuing with non-sustained ventricular tachycardias (NSVT) and sustained ventricular tachycardias (VT) with appropriate ICD therapies, both in the form of antitachycardia pacing (ATP) and defibrillation shocks. In addition, prolonged and symptomatic episodes of atrial flutter with a rapid ventricular response since 2017, requiring adjustment of medical treatment and parameters of ICD-CRT without achieving an optimal percentage of biventricular stimulation, staying below 90% () (ECG of the arrhythmic episodes in the ).
In addition, our patient suffered several episodes of decompensated HF in the context of respiratory infection and the arrhythmic episodes described above, with more than eight visits to the Emergency Department and the Cardiology Day Hospital between the beginning of 2018 and June 2019, with intravenous diuretic treatment and adjustment of outpatient regimen.
Given this situation of multiple decompensations and arrhythmic episodes despite optimized treatment, the possibility of implanting a Barostim Neo® device for symptomatic improvement and the possibility of reducing arrhythmic events was considered, because we had no more possibilities for medical treatment or device optimization. The case was presented in session with a multidisciplinary Heart Team (cardiology, cardiac surgery, and anaesthesiology), approving the procedure, which was carried out in July 2019 without incidents ().
After device activation, there were no complications or discomfort associated with the implant or therapy. Blood pressure remained stable and without interaction with the ICD-CRT function, being monitored both at implantation and activation and at each control visit ().
In the follow-up after activation of the device, the patient has not had any decompensation of HF, without consulting the emergency room or increasing diuretic therapy, and with outpatient infusions of Levosimendan every 6 weeks instead of every 4 weeks.
In addition, a very significant decrease in arrhythmic episodes monitored with ICD-CRT was observed: more than 480 episodes of NSVT were monitored prior to implantation, with three episodes of VT with adequate ICD therapy (with ATP, without shock), a 7.4% of the time in AT/AF, and with <90% biventricular stimulation. The number of arrhythmic episodes had decreased to almost disappear in the last revision of the device in October 2019, without the need for ICD therapy and increasing the percentage of biventricular stimulation reaching almost 97% (). An improvement in N-terminal of the pro-natriuretic peptide type (NT-proBNP) and renal function levels had also been observed. There were no significant changes in the distance covered in the 6-min walk test (). Signs of pulmonary congestion and peripheral oedema gradually disappeared on subsequent visits.


A 48-year-old Japanese woman, gravida 6, para 3 (3 vaginal deliveries and 3 miscarriages) presented with heavy menstrual bleeding. Cytology of the uterine cervix and endometrium were negative for intraepithelial lesion of malignancy (NILM) and negative, respectively. Magnetic resonance imaging (MRI) revealed a 14-cm leiomyoma in the anterior wall of the uterine cervix and no other prominent tumor was found. Gonadotropin-releasing hormone analog (GnRHa) was omitted because we expected TLH was possible without administering it. The surgical procedure was performed as follows: (1) a total of four ports were inserted in a diamond pattern. The round ligaments, mesosalpinx, and utero-ovarian ligaments were sectioned. Both ovaries were preserved, (2) after identifying the uterine artery and ureter, the former was ligated twice. Then, the ureters were isolated from the posterior leaf of the broad ligament to the ureteral tunnel, (3) the vesicouterine peritoneum was opened, and the bladder was pushed down from the uterine anterior wall as much as possible, 4) the parametrium was coagulated and incised including the ascending branch of the uterine artery. The flattened parametrium caused by the cervical myoma resulted in a widened and deviated to the posterior part of the myoma, thus making the procedure more challenging, (5) a malleable retractor was inserted into the anterior fornix of the vagina, and the anterior part was incised followed by the circumferential dissection of the vagina, (6) completion of colpotomy was performed in a retrograde fashion by incising the uterosacral ligaments and posterior leaf of the broad ligaments, (7) The uterus was transvaginally removed in small pieces, and (8) the vaginal vault was sutured laparoscopically.
The procedure lasted for 121 min, with intraoperative blood loss of 200 ml. The weight of the removed uterus was 888 g, and the pathological examination was consistent with a benign leiomyoma. The postoperative course was uneventful, and the patient was discharged on a postoperative day 3 without complications.


A 55-year-old Japanese woman, gravida 2, para 2 (1 vaginal delivery and 1 cesarean section) presented with heavy menstrual bleeding and pollakisuria. Cytology of the uterine cervix was NILM and of the endometrium was negative. MRI revealed a 15.9-cm leiomyoma in the anterior wall of the uterine cervix with no other prominent tumors found. GnRHa was administrated five times preoperatively. The size of the myoma became slightly smaller, that is, 13.4 cm before the surgery. The surgical procedure was essentially the same as in case 1. However, due to the further caudally positioned cervical myoma than that in case 1, the incision of the parametrium was difficult at one side and resulted in a relatively large amount of bleeding.
The procedure lasted for 209 min, with intraoperative blood loss of 400 ml. She received 400 ml of autologous blood. The weight of the removed uterus was 1130 g, and the pathological examination was consistent with a benign leiomyoma. The patient was discharged on a postoperative day 3 without complications.


A 50-year-old Japanese woman, gravida 2, para 2 (2 vaginal deliveries) presented with abdominal distension and abnormal genital bleeding. Cytology of the uterine cervix was NILM and of the endometrium was not fulfilled. MRI revealed a 13.7-cm leiomyoma in the anterior wall of the uterine cervix and another 3-cm leiomyoma in the anterior uterine corpus. GnRHa was administrated four times and found to be noneffective. The surgical procedure has essentially started as in case 2. However, the view of the surgical field could not be achieved safely, and the complete incision of both parametrium was not possible considering the bulging cervical myoma expanded more to the anterior and caudal sides than that in case 2. Therefore, open surgery and subsequent uterus removal were done.
The operation lasted for 197 min and the intraoperative blood loss was 1280 ml. She received 400 ml of autologous blood. The weight of the removed uterus was 1182 g, and the pathological result was degenerative leiomyoma. The postoperative course was uneventful, and the patient was discharged on a postoperative day 5 without complications.


A 50-year-old gravida 2 para 2 woman presented at our hospital for a regular checkup for breast cancer. She had a family history of breast cancer on her maternal side and had undergone surgery for right breast cancer at the age of 43. For the past 6 years, she had taken tamoxifen and was followed up for cervical cytology. She also had childhood asthma and an appendectomy at the age of 12. She had complained of excessive menstruation, and a hot spot in the uterine lumen was detected using positron emission tomography–computed tomography (PET-CT) at the breast surgery department. She was referred to the obstetrics and gynecology department for further examination and treatment.
Physical and abdominal examination findings were normal. The results of the pelvic examination finding were also normal. Transvaginal ultrasonography revealed a 21.8-mm uterine mass and an enlarged right ovary. Cervical cytology was negative for malignant intraepithelial lesions. Endometrial cytology was negative. Her blood test showed a hemoglobin level of 8.7 g/dL and hematocrit of 29.2%. Laboratory findings such as platelet count and solidification systems were normal, and tumor markers including CA-125 and CA-19-9 were negative.
Pelvic magnetic resonance imaging (MRI) was performed to examine the uterine mass, which revealed an endometrial polyp and submucosal leiomyoma in the uterine lumen and a 5-cm right ovarian tumor []. The MRI signal pattern suggested that the right ovarian tumor was a fibroma or thecoma. Thus, the cause of anemia was thought to be due to the endometrial polyp and submucosal leiomyoma. Therefore, she underwent laparoscopic surgery under the clinical diagnosis of endometrial polyp, submucosal leiomyoma, and right ovarian tumor for polyp, leiomyoma, and tumor excision, respectively.
Laparoscopy showed that the right ovarian tumor was approximately 5 cm in diameter, a white solid tumor, suggestive of a fibroma or thecoma. The uterus was slightly enlarged. Laparoscopic total hysterectomy, right salpingo-oophorectomy, and left salpingectomy were performed. Tissues were excised out vaginally. Uterus and ovarian tumor weights were 276 g and 57 g, respectively. Surgery time was 163 min, and the amount of bleeding was 100 ml.
Histopathological examination revealed polyp-like ridges containing interlacing endometrial glands with mild alignment disorder and endometrial stroma in the uterine endometrium. There were ectopic endometrial tissues in the uterine muscle layer and serosal surface and some uterine intramural leiomyomas (maximum 6-mm diameter). The ovarian tumor measured 5.5 cm × 3 cm × 3 cm, and the cut section of the tumor showed a hard gray-white solid area which was well encapsulated []. Furthermore, the ovarian tumor contained interlacing bundles of fusiform cells with wide fibrosis and hyalinization. The cell density of the ovarian tumor was low. Nuclear atypia, pleomorphism, and necrosis were absent. The mitotic count was <1/10 high-power fields []. Immunohistochemical staining showed strong and diffuse positive staining for α-smooth muscle actin (α-SMA) [].
The diagnosis was endometrial polyps, uterine adenomyosis, and intramural leiomyomas and an ovarian leiomyoma. The ovarian leiomyoma was larger than any other uterine leiomyomas, and there were no findings of metastatic leiomyomas on PET-CT. Therefore, the final diagnosis was a primary ovarian leiomyoma. The postoperative period was uneventful. Her blood test showed a hemoglobin level of 6.0 g/dL 1 day after surgery and 8.3 g/dL with iron administration 1 week after surgery. At the 6-month follow-up, the patient had no complaints and no signs of tumor recurrence.


A 12-year-old girl medically free presented with fever, loin pain and hematuria on February 26, 2020. Her laboratory work revealed anemia (hemoglobin level 8.4 g/dL, reference range: 11.5-15.5 g/dL) with normal platelets and white blood cells count.
Based on clinical presentation and laboratory data, diagnosed as urinary tract infection and iron deficiency anemia, she was discharged on cefprozil and oral iron supplements. Her other investigations showed normal chest x-ray (CXR) and negative urine culture.
After two weeks from initial presentation, she had developed dry cough and her family sought medical advice in many medical centers as her cough getting worse without improvement. On the 17th of March, the patient admitted to our institution complaining of worsening dry cough with no fever. Cough was associated with left sided chest pain, which increased with movement and deep breathing. She denied any history of contact with patient with confirmed COVID- 19 or any respiratory diseases. No history of travel or contact with any person with travel history. She had no gastrointestinal symptoms, joints pain, or skin rash. No family history of thrombosis or similar illness. On physical examination, the child was clinically stable with normal vital signs including body temperature as well as blood pressure. She was not in respiratory distress and saturated well in room air. Chest examination revealed normal contour, good air entry on the right side, and diminished air entry on the left side with no bronchial breathing or wheeze.
CXR showed opacity involving the left lung base laterally with obliteration of the left costophrenic angle ().
The laboratory investigations at admission are summarized in , showed mild lymphopenia and normal WBC, but later on she developed leukopenia and severe lymphopenia. Kidney and liver function were normal. On the next day of admission both D-dimer level and anti- Phosphatidylserine (IgG and IgM) were elevated whereas other thrombophilia panels were negative (D-Dimer: 4.590, reference range 0.000-0.500 ug/mL, IgG Anti- Phosphatidylserine: 39, reference range 0-1 U/mL, IgM Anti-Phosphatidylserine: 39, reference range 0-24 U/mL). Fibrinogen was normal: 3.8 (reference range 2.0-5.0 g/L). Procalcitoninwas elevated as well: 6.29 (reference range 0.10-0.49 ng/mL).
Because of CXR findings, computed tomography pulmonary angiography (CTPA) had been performed on the next day of admission and revealed extensive bilateral pulmonary embolisms (PE) with multiple peripheral subpleural infarctions and peripheral subpleural ground-glass opacity of the right upper lobe (). The patient started initially from ceftriaxone and received a course of azithromycin as a treatment of atypical community acquired pneumonia with unusual PE for investigation.
Immediately, hematology and cardiology services evaluated the patient condition and documented the stability of the cardiorespiratory condition with no hematuria or potential risk of bleeding. To look for the source of PE, doppler ultrasonography of the lower limbs and echocardiography was reported as normal with no detected thrombi. Electrocardiogram testing was performed as well and revealed normal sinus rhythm with neither right ventricular hypertrophy nor ST segment abnormalities. Multidisciplinary team decided to start the child from subcutaneous low molecular weight heparin (enoxaparin 1 mg/kg with a total dose of 30 mg subcutaneous every 12 hours). Based on the follow up of therapeutic anti-X level, enoxaparin adjusted to 40 mg s/c every 12 hours to keep the therapeutic level at the higher side 0.75-1.0 IU/mL.
On 25th of March, follow up CTPA showed the same features of PE and infarction as previous imaging. The child remains afebrile and clinically stable with no signs of respiratory distress until 28th of March (11 days after admission) when she started to have frequent spikes of fever up to 39.5°C with no respiratory distress and her laboratory testing revealed leucopenia and severe lymphopenia (0.6×109/L). Although she had been on broad-spectrum intravenous antibiotics, which were escalated to a combination of tazocin and vancomycin, her body temperature continued to spike daily. Antimicrobials therapy was stopped after the microbiological laboratories had reported negative blood cultures on multiple occasions.
Due to the clinical manifestations of persistent fever and dry cough, radiological features of ground glass appearance and PE, in addition to laboratory testing of progressive leucopenia and lymphopenia, COVID- 19 was suspected. On March 31st, COVID- 19 testing was performed by (rRT-PCR) of nasopharyngeal swab. While waiting the COVID-19 rRT-PCR result, the patient was started on daily oral hydroxylchloroquine 200 mg as a suspected with antiphospholipid syndrome because of PE and associated elevation of both antinuclear and antiphospholipid antibodies with elevated ESR and CRP
Three days later, COVID-19 rRT-PCR results reported as positive which led to the addition of azithromycin to hydroxychloroquine. The child remained clinically stable, afebrile, and on room air without any cardiorespiratory assistance. After two COVID-19 negative serial RT-PCR for SARS-CoV-2 RNA from the nasopharyngeal swab, she was discharged home from anticoagulant therapy in a good condition with a repeat of CTPA in two weeks from discharge for evaluation of her clinical condition.


A 63-year-old man presented with 2 months of cough, fever, intermittent night sweats, and 10 lbs of unintentional weight loss. Computed tomography scan showed pulmonary opacities and indeterminate mediastinal and hilar lymphadenopathy. Levofloxacin was administered without improvement, so a bronchoscopy with endobronchial ultrasound was performed. Needle aspiration of a lymph node yielded necrotic tissue without evidence of malignancy. Bacterial culture of bronchoalveolar lavage had no growth; stain for acid fast bacilli (AFB) was negative. Despite continued antibiotic administration, the fevers persisted. Skin lesions appeared, as well as pain and swelling of his wrists, elbows, knees, and ankles. A pustule developed at the site of a tuberculin purified protein derivative skin test 72 hours after placement. Two skin biopsies were nondiagnostic. The patient was transferred to our hospital for further evaluation.
The patient was born and raised in Laos where he was an irrigation engineer. He and his family immigrated to the United States decades ago and settled in Northwest Arkansas where he worked as a school custodian. His hobbies included gardening. He was not sexually active, and he never used illicit drugs. His last international travel was 6 years ago when he visited Laos and Japan.
On arrival to our hospital, the patient complained of pain related to swelling of his extremities and skin lesions. He did not have cough or other respiratory symptoms. Temperature was 102.8 °F, blood pressure was 163/85 mm Hg, heart rate was 118 beats per minute, and respiratory rate was 18 breaths per minute. There were no ocular abnormalities, oral lesions, or lymphadenopathy. Skin examination was remarkable for dusky, hemorrhagic pustules, bullae that were most prominent on bilateral proximal palms, and erythematous papules and pustules on bilateral arms, knees, ankles, and dorsal feet, with increased density proximal to joints ( and ). There was tight edema of all distal extremities. Previous skin biopsy sites had purulent drainage. This finding and the reaction to intradermal injection of tuberculin PPD suggested pathergy, an exaggerated inflammatory response to local skin injury.
Laboratory results showed white blood cell count of 16.2 K/mm3 with 84% polymorphonuclear leukocytes, C-reactive protein of 15.9 mg/dL, and erythrocyte sedimentation rate of >130 mm/h. Numerous blood cultures had no growth. Culture of purulent material from the site of previous skin biopsy was negative. Aspiration of the left ankle yielded 1 cc of blood-tinged fluid, which was not of sufficient quantity to send for analysis. Fourth-generation HIV testing was nonreactive. Multiple expectorated sputum specimens stained negatively for AFB and tested negatively for Mycobacterium tuberculosis DNA by polymerase chain reaction.


A previously healthy 33-year-old male with no medical comorbidities, a nonsmoker not consuming alcohol or drugs whose family history did not include any endocrine disorders or cancer syndromes and who denied any history of radiation exposure, hoarseness, dysphagia, weight loss, flushing or diarrhea, presented in October 2017 with a palpable thyroid mass in the left cervical region. Physical examination revealed a rhythmic heart rate of 80 bpm, blood pressure at 110/70 mm Hg, oxygen saturation assessed by pulse oximeter at 94% at room air, and a palpable left thyroid mass of approximately 1-cm diameter, which was nonpainful and nonmobile with a soft consistency.
A thyroid profile was requested, with antithyroglobulin antibody at 160 (normal range 0–40) and carcinoembryonic antigen (CEA) at 0.84 ng/mL (range 0–3); thyroid function and calcium levels were both within normal range. Calcitonin, parathyroid hormone, and urine and plasma metanephrines were not measured. On November 17, 2017, ultrasonography-guided fine-needle aspiration (FNA) of the lymph node (levels III and IV) was performed, which highlighted findings suggestive of large-cell lymphoma. Also, thyroid nodule FNA was conducted, showing atypical lymphoid proliferation suggestive of lymphoma (Bethesda VI) with areas indicative of nonconclusive papillary thyroid cancer.
On November 24, 2017, lymphadenectomy with thyroid nodule FNA was performed, with the histopathological report of high-grade neuroendocrine carcinoma of the thyroid nodule, negative for calcitonin and metastatic to the lymph node, compatible with a thyroid primary. Immunohistochemical analyses were carried out, which demonstrated to be calcitonin, chromogranin A, CEA and thyroglobulin negative, synaptophysin positive in 30%, CD56 positive in 70%, and TTF-1 positive in 5%; the Ki-67 proliferation index was as high as 90% (Fig. ).
18F-FDG-PET/CT was conducted on December 2017 outlining a tumor dependent on the left lobe of the thyroid, as well as multiple cervical and mediastinal adenopathies with increased metabolism (Fig. ). It was confirmed as calcitonin-negative neuroendocrine carcinoma of the thyroid gland, clinical status IVA (T3N1bM0). The patient started chemotherapy on December 12, 2017, with etoposide and cisplatin. He received 6 chemotherapy cycles as neoadjuvant treatment. In March 2018, total thyroidectomy plus bilateral and central cervical dissection was performed. He received 2 cycles of adjuvant radiotherapy. Currently, 18F-FDG-PET/CT showed a complete response 17 months after diagnosis (Fig. ).


A 64-year-old female underwent radical right lower lobectomy surgery due to lung cancer (squamous cell carcinoma, pT1aN0M0) 6 years ago. However, 1 year ago, mediastinal nodal metastasis was detected by 18F-fluorodeoxyglucose (18F-FDG) PET/CT and proved pathologically to have mediastinal nodal metastasis by mediastinoscopy (the expression of programmed cell death 1 was 95%). Pembrolizumab as the first-line therapy continued for 1 year (15 cycles); however, the patient complained of right hip pain. Bone SPECT/CT with 99mTc hydroxymethylene diphosphonate (99mTc-HMDP, Nihon Medi-Physics Co. Ltd, Tokyo, Japan) showed focal and intense uptake by the right femur head and faint uptake by the left ribs (third and eighth; Fig. ), and bony metastasis was confirmed by MRI. She received palliative radiotherapy (20 Gy/5 Fr) for the right femur head metastasis. Carboplatin and nab-paclitaxel was started as the second-line therapy; however, 4 months later CT showed the appearance of lung metastasis and adrenal metastasis. Fluorouracil was started as the third-line therapy; however, 2 months later a second bone SPECT/CT (8 months after the first bone SPECT/CT) showed a decrease of the right femur head uptake, increase in the uptake by the left ribs, and the appearance of new uptake in the sternum, right rib, spine (Th2, Th9, Th12, L4, S1), and bilateral pelvic bone (left ilium, acetabular cartridge, femur, right ilium and ischium; Fig. ). The serum CEA and CA19-9 on the first and second 99mTc-HMDP bone SPECT/CT increased from 41.9 to 602 ng/mL (1,336.8% increase) and 267 to 8,555 U/mL (3,104.1% increase), respectively.
Two bone SPECT/CT scans using an integrated SPECT/CT system (Discovery NM/CT 670, GE Healthcare) equipped with a low-energy high-resolution collimator were performed 3 h after intravenous injection of 555 MBq of 99mTc-HMDP. SPECT/CT data were analyzed using a commercially available software package (GI-BONE, Aze Co. Ltd, Tokyo, Japan), which provides statistics for various SUVs, such as the maximum, peak, and mean SUV, as well as the metabolic bone volume (MBV) and total bone uptake (TBU) []. The SUVmax was defined as the maximum concentration in the target lesion: (maximum radioactivity/voxel volume)/(injected radioactivity/body weight). The SUVpeak was defined as the average activity concentration within a 1-cm3 spherical volume of interest (VOI) centered on the “hottest focus” within the tumor. The SUVmean was defined as: (total radioactivity/VOI volume)/(injected radioactivity/body weight). The MBV (cm3) was the calculated volume obtained by the radiopharmaceutical accumulation by placing the tumor VOI with the margin threshold set at 40% of the SUVmax. The TBU was then calculated as the SUVmean × MBV. The bone scan index (BSI) was automatically calculated by two-dimensional planar imaging (anterior and posterior images) [].
The change of SUVmax, SUVpeak, SUVmean, MBV, and TBU for right femur head metastasis was −72.6% (from 22.96 to 6.28), −70.4% (from 19.66 to 5.82), −64.5% (from 12.98 to 4.61), −35.1% (from 14.70 to 9.54 cm3), and −77.0% (from 190.81 to 43.97), respectively (Fig. ). The change of SUVmax, SUVpeak, SUVmean, MBV, and TBU for left third rib metastasis was +407.7% (from 2.97 to 15.08), +416.7% (from 2.33 to 12.04), +392.8% (from 1.80 to 8.87), +31.0% (from 5.46 to 7.15 cm3), and +545.1% (from 9.82 to 63.35), respectively. The change of SUVmax, SUVpeak, SUVmean, MBV, and TBU for left eighth rib metastasis was +229.2% (from 2.60 to 8.56), +236.7% (from 2.10 to 7.07), +226.2% (from 1.68 to 5.48), +30.9% (from 2.59 to 3.39 cm3), and +325.2% (from 4.37 to 18.58), respectively. The SUVmax, SUVpeak, SUVmean, MBV, and TBU of left ileum metastasis on the second bone SPECT/CT were 19.91, 18.56, 12.27, 21.53 cm3, and 264.12, respectively. The SUVmax, SUVpeak, SUVmean, MBV, and TBU of sternum metastasis on the second bone SPECT/CT were 12.77, 10.14, 7.49, 5.09 cm3, and 38.11, respectively. The SUVmax, SUVpeak, SUVmean, MBV, and TBU of right ileum metastasis on the second bone SPECT/CT were 12.90, 11.30, 7.88, 10.51 cm3, and 82.8, respectively. The SUVmax, SUVpeak, SUVmean, MBV, and TBU of sacrum metastasis on the second bone SPECT/CT were 9.11, 8.47, 5.79, 11.95 cm3, and 69.21, respectively. The SUVmax, SUVpeak, SUVmean, MBV, and TBU of thoracic vertebrae Th9 metastasis on the second bone SPECT/CT were 17.25, 14.43, 10.36, 7.14 cm3, and 73.95, respectively. The change of whole-lesion MBV and TBU was +235.4% (from 22.75 to 76.3 cm3) and +219.1% (from 205.0 to 654.09), respectively. On the other hand, the change of BSI was +797.5% (from 0.4 to 3.59%). Two quantitative bone SPECT/CT images clearly showed the good response of the femur head metastasis to radiotherapy, and progression of other bone metastases regardless of chemotherapy.


A 15-year-old girl presented with right-buttock pain for 2 months. She had no history of trauma, and her medical history was unremarkable. On physical examination at our hospital, she had pain on movement in her right hip. However, there was no swelling, redness, or burning sensation in the same area. There were no significant neurological findings, such as numbness or muscle weakness in the lower extremities.
Blood investigations revealed a white blood cell count and C-reactive protein level of 4.9 × 109 cells/L (neutrophils, 59.0%; lymphocytes, 36.0%; monocytes, 4.0%) and 1.69 mg/dL (normal: <0.30), respectively. On radiological investigations, her X-ray scans showed no obvious bone destruction (Fig.); however, a destructive lesion on the right side of the S2 sacrum with no calcification was observed on computed tomography (CT) (Fig. ). On magnetic resonance imaging, the lesion measured 63 × 30 × 11 mm; it was isointense on T1-weighted imaging and showed mixed low-high signal intensity on short TI inversion recovery-weighted imaging. The signal changes expanded beyond the mid-sacral region and into the spinal canal (Fig. ). The results of a chest CT scan and positron emission tomography-CT performed to rule out metastatic disease were negative. Based on these findings, we suspected that the lesion was an osteomyelitis or ES. An open incisional biopsy was performed. Histologically, the tumor was composed of circular cells that were proliferating in a cord-like, part-sheet-like structure, and were necrotic (Fig. ). Immunohistochemical analysis revealed that the tumor was positive for CD99 (Fig. ). A diagnosis of ES was made. This was supported by fluorescence in situ hybridization, which showed an ESWR1 split signal in 54% and an FLI1 split signal in 56% (Fig. ).
The patient was treated with neoadjuvant chemotherapy using the VDC/IE regimen comprising vincristine, doxorubicin, and cyclophosphamide alternating with cycles of ifosfamide and etoposide. The chemotherapy caused 73% tumor shrinkage (Fig. ). We performed wide excision and reconstruction.
First, the patient was placed in the supine position and administered general anesthesia. The incision that was taken in the supine position. We ligated the anterior sacral artery and sacral venous plexus in front of the tumor to reduce intraoperative bleeding. Subsequently, the patient was re-placed in the prone position. A posterior midline incision was made extending from L2 to S4. For the partial sacral resection, the sacrum was resected at the level of the S1 sacral foramen (Fig. ). The right sacroiliac joint was included and the left side was resected in the form of a connecting sacral foramen. The cauda equina was severed at the S2 level with the dural canal ligated at the cranial side. The sacral resection was then reconstructed using an allogeneic tibial strut bone graft. L3 to the iliac bone was fixed posteriorly with a dual rod. Moreover, sufficient bone grafting was performed and the allogeneic fibula bone chip was grafted in L3 to the iliac bone (Fig. ).
A blood transfusion was required based on an estimated intraoperative blood loss of 4,900 mL. Histological analysis of the tumor specimens revealed no tumor cells at the tissue margins.
Immediately after surgery, DigniCare (Bard Medical Division, C. R. Bard, Inc., Covington, GA, USA) was used for 2 weeks to drain stool via the rectum to avoid contamination of the wound. Full-weight gait training was started 2 weeks postoperatively, and postoperative chemotherapy was started on day 31 after surgery, when the wound was completely healed. Radiotherapy was not performed, because the tumor was removed with wide margins and there were no viable tumor cells.
At 1 year and 3 months postoperatively, the patient was free of disease (Fig. ). There was no osteolysis of the reconstructed area and no implant failure. The patient was pain free; she had resumed exercising and could independently perform her daily activities without a cane. However, she has a bladder-rectal disorder and is self-catheterizing. Her Musculoskeletal Society Tumor score (MSTS) was 30 and the Toronto Extremity Salvage Score (TESS) was 99.2 (119/120).


A 52-year-old female presented to a local general hospital with the chief complaint of tenesmus and continuous rectal bleeding of several months duration. She reported no history of cutaneous melanoma and denied hypertension and diabetes mellitus. A perianal visual and digital examination showed a bleeding pedunculated mass sticking out from the anus and a huge hemorrhoid at 6 o’clock. A complete excision of the anal mass and hemorrhoidectomy were performed. The microscopic evaluation of the excised anal mass showed evidence of malignant melanoma with positive stains in immunohistochemistry for Human Melanoma Black 45 (HMB-45) and melan-A. The experts at the local hospital did not have much experience with anorectal melanoma, so the patient was transferred to our hospital.
Colonoscopy, computed tomography (CT) of the thorax-abdomen, and magnetic resonance imaging (MRI) of the pelvis were performed for the purpose of staging the disease. The colonoscopy revealed a small ulcerated area (8 mm in diameter) 1.5 cm from the anal verge. CT of the thorax-abdomen demonstrated no evidence of lymph nodes or distant metastases. MRI confirmed a well preserved anorectal fat plane and several small regional lymph nodes at the perirectal space ().
The patient was diagnosed with anal melanoma, and her case was discussed at a multidisciplinary meeting. Due to the high suspicion of regional lymph nodes metastasis and the extended length of time from the onset of initial symptoms, an abdominoperineal resection (APR) was performed. She underwent laparoscopic-assisted APR along with left-side end colostomy and tolerated the surgical procedure without any complications. Evaluation of the pathologic specimen confirmed no evidence of a malignant lesion located in the anorectal wall. One of 4 regional lymph nodes was found to be positive for metastasis. Subsequently, she received adjuvant chemotherapy with a combination of cisplatin, vinblastine, and dacarbazine. At the 6-month follow-up visit, no evidence of metastasis was observed.


A 39-year-old female with an unremarkable history underwent transanal excision of a polyp of the anal canal. The specimen consisted of a polypoid mass measuring 2.5× 2.3 cm. The histopathological examination showed malignant melanoma and a clear resection, and the HMB-45 immunohistochemical stain result was positive. She visited our hospital for consultation about possible remnant tumor and the risk of recurrence. Therefore, we performed a series of tests to identify the stage of the disease.
Colonoscopy confirmed no evidence of residual tumor, and there was a previous operative scar at the dentate line. Five biopsies were performed, all of which were negative for anorectal carcinoma. MRI of the rectum showed 2 residual lymph node metastases in the left lateral pelvic sidewall along the internal iliac axis and 2 other lymph node metastases in the left obturator and lateral sacral area. No demonstrable residual primary lesions were seen in the rectum. Positron emission tomography (PET)/CT showed a focal fluorodeoxyglucose (FDG) uptake in the anal canal, which was attributed to postexcisional inflammatory change, and 2 round nodular lesions in the left perirectal area and left presacral pelvic with no discernible FDG uptake.
After consultation at a multidisciplinary team meeting, we decided that she would undergo laparoscopic ultralow anterior resection (ULAR) with coloanal anastomosis and diversion ileostomy, and she had an uncomplicated recovery. Gross examination showed a small scar located at the dentate line which corresponded to the lesion from the first transanal operation. The histopathological report showed no residual malignant melanoma and metastatic malignant melanoma in 1 out of 42 regional lymph nodes in the following location; left internal iliac (0 of 5), inferior mesenteric artery (0 of 4), left common iliac (0 of 9), left obturator (1 of 9) and regional (0 of 15). The proximal and distal margins were free from tumor. She received immunotherapy (high-dose interferon [IFN]), and 13 months after the primary operation, she underwent ileostomy repair at which time there was no evidence of recurrence.
Sixteen months after the ULAR operation, a CT of the abdomen-pelvis demonstrated metastatic lymph nodes in the aortocaval space, and radiotherapy was initiated due to the evidence of recurrence ().


A male 59-year-old patient was admitted to the Dr. Soetomo General Hospital with hematemesis and melena. The patient complained of hematemesis for 6 h before admission. He vomited three times with an amount of 200–300 mL and had lower abdominal pain. Defecate black liquid twice since 6 h before admission with a very bad smell. The patient complained of dizziness accompanied by nausea and had no appetite since 5 days. There had been shortness of breath when performing heavy activity, reduced when resting and absence of fever.
The patient had a history of diabetes mellitus since 3 years. He was under insulin and oral medication but irregularly. History of hypertension, heart, lung, and kidney diseases was denied. There was a history of consuming medicinal herbs for myalgia. The patient consumed it every day. He felt weak when he did not drink. He used this drug for the past 5 months. Psycho-social history: he works as a construction worker and is smoking three packs a day since youth.
On physical examination, it was found with compos mentis GCS 456 that his blood pressure was 125/75 mm Hg, heart rate was 96 ×/min regular, strong pulse, adequate content, respiratory rate was 20 ×/min, the axillary temperature was 36.5°C, and SpO2 was 99% of free air. The examination of head and neck conjunctiva anemic was present, no jaundice, no cyanosis, no dyspnea, no enlarged lymph nodes, jugular venous pressure does not increase. The thorax was normal, the abdomen appeared flat and there was no palpable mass, liver and spleen enlargement were not palpable, he had normal bowel sounds, and abdominal pain in the umbilical region. Extremities were warm, dry acral, capillary refill time <2 s. No edema was found on both legs.
Laboratory tests showed that his Hb was 8.3 g/dL, hematocrit was 23.6%, MCV 78.1; MCH 27.5; MCHC 35.2; platelets were 356,000 mm3, leukocytes were 14,369 mm3, neutrophils were 79.1%, lymphocytes were 14.5%, sodium was 132 mmol/L, potassium was 4.4 mmol/L, chloride was 106 mmol/L, HbA1C was 11.2%, random blood sugar was 202 mg/dL, SGOT was 16 U/L, SGPT was 27 U/L, blood urea nitrogen (BUN) was 28 mg/dL, serum creatinine was 1.14 mg/dL, and albumin was 3 g/dL. The examination of chest radiograph showed normal heart and lungs.
The patient was treated with a B1 soft diet 2,100 kcal/day, infusion of NaCl 0.9% 1,500 mL in 24 h i.v., injection of omeprazole 40 mg every 8 h i.v., sucralfat syrup 15 mL every 8 h orally, novorapid injection 4 units every 8 h sc ac 15 min, transfusion of packed red cells (PRC) 1 bag/day until Hb >10 g/dL, metoclopramide 10 mg every 8 h i.v., amlodipin 10 mg every 24 h orally, lactulac syrup 15 mL every 8 h orally, Ceftriaxon 1 g every 12 h i.v., and paracetamol 500 mg every 8 h orally.
The patient had been given PRC transfusion until Hb reached 10.3 g/dL, and the upper gastrointestinal EGD showed that the cause of bleeding to this patient was a gastric ulcer which was suspected and caused by consumption of medicinal herbs. At EGD, double pylorus was accompanied by giant white ulcer with a partially covered in clotting without any sign of active bleeding. It could be concluded that there was a double pylorus with giant ulcer, Forrest IIb (Fig. ).
After 1 week of treatment at Dr. Soetomo General Hospital, the patient's complaints were improved and he had no nausea nor vomiting, there were no hematemesis and melena, and his appetite was improved. The patient was discharged from hospital. Planning therapy was B1 soft diet 2,100 kcal/day, omeprazole 20 mg every 12 h per oral, sucralfat syrup 15 mL every 8 h orally, novorapid injection 4 units every 8 h sc ac 15 min, amlodipin 10 mg every 24 h orally. Biopsy revealed chronic inactive gastritis, and no H. pylori was detected. The patient underwent checkup at the Gastroenterology department after 1 week of hospital discharge with complaints of decreased appetite, abdominal pain, and no nausea and received sucralfate syrup and lansoprazole orally.


A 64-year-old male patient was admitted to our hospital's gastroenterology department. The patient had no specific medical history, except for dyslipidemia, and complained of rectal tenesmus, lasting for 1 month, and anal pain, which had progressively worsened for 10 days. At the time of arrival, stool occult blood test was negative and no relevant findings in other laboratory results were identified. An 8-mm polyp in the ascending colon was detected during colonoscopy, and hyperemic mucosal swelling with nodularity was noted at 4–17 cm from the anal verge (Fig. ). Biopsies performed for each lesion indicated adenoma and chronic colitis, respectively. Diffuse swelling throughout the rectum was seen on CT, and engorgement of the superior rectal veins with early draining was also observed (Fig. ). AVM-related venous hypertension was suspected as the cause of symptoms, and angiography was requested. On angiography performed 3 days later, rectal AVM was identified at the inferior mesenteric artery just before the beginning of the superior rectal arteries and was drained via fine feeders into the inferior mesenteric vein with a large venous aneurysm (Fig. ). Venous regurgitation by venous hypertension was also clearly observed through the retrograde flow of the superior rectal veins (Fig. ). After an in-depth discussion with the patient about the options for surgery or other endovascular embolization, transarterial sclerotherapy using ethanol was decided. After selection to the far distal feeding artery using a microcatheter, sclerotherapy was performed several times using a total of 5 mL of 80% ethanol (Fig. ), while shunt was gradually reduced in serial follow-up angiography. To prevent venous thrombosis, 2,000 units of heparin were intravenously administered during the procedure. The early arteriovenous shunt was completely lost in completion angiography, and a little spasm was observed in the distal branch of the superior rectal arteries (Fig. ). The spasm improved after intra-arterial infusion of 1,000,000 units of nitroglycerin, and the procedure was terminated. There were no acute complications except for analgesic-controlled buttock pain. Follow-up CT performed 2 weeks later revealed reduced rectal wall edema, AVM nidus disappearance, and thrombosed venous sac (Fig. ). In addition, engorgement and early draining of the superior rectal veins were also lost. The main symptoms, such as rectal tenesmus and anal pain, gradually improved within 1 week of hospitalization and did not recur during clinical follow-up for 10 months.


A 67-year-old Caucasian male had resection of a right axillary dedifferentiated liposarcoma in May 2013 with positive margins followed by adjuvant radiation. In January 2016, he had biopsy-proven local recurrence without metastatic disease. He had stable disease with 8 cycles of doxorubicin and olaratumab followed by 8 cycles of maintenance olaratumab. He had disease progression and was treated with gemcitabine and docetaxel. In February 2018, due to disease progression, he was switched to pazopanib. His course was complicated by soft tissue infection related to the axillary mass and systolic heart failure attributed to anthracycline-related cardiomyopathy in the setting of increased afterload from tyrosine kinase inhibitor (left ventricular ejection fraction 21%). In April 2018, PET scan showed progression of right axillary mass and diffuse metastatic disease involving the lungs, pleura, and liver. The patient began off-label treatment with ipilimumab (1 mg/kg) and nivolumab (3 mg/kg) every 3 weeks for four cycles followed by maintenance nivolumab (3 mg/kg) every 2 weeks. His cardiac function recovered shortly after starting ipilimumab/nivolumab. The patient received concurrent cryoablation of the right axillary mass in June 2018 (Fig. ). Subsequent restaging CT scans demonstrated a significant response in the right axillary mass, pulmonary nodules, and liver lesions (Fig. ). After completion of four cycles of ipilimumab and nivolumab and two cycles of maintenance nivolumab, he developed autoimmune colitis and was treated with prednisone taper for 8 weeks. He developed pneumonia in the setting of immunosuppression that was complicated by bacteremia and atrial fibrillation and experienced an acute decline in cardiac function. After hospital discharge, he continued maintenance nivolumab at 6 mg/kg every 4 weeks. He remained on maintenance nivolumab, with impressive radiographic and clinical response including disappearance of his axillary mass. In December 2018, he passed away from sudden cardiac death.


A 66-year-old Asian female had margin negative resection of myxofibrosarcoma of the right calf in March 2012 followed by adjuvant radiation. In May 2013, she had a margin negative resection of a recurrence in her right upper thigh. In August 2015, she had a resection of a recurrence extending to more proximal thigh and pelvis followed by radiation. In August 2016, she had resection of right upper thigh and gluteus minimus sarcoma. She started treatment with pazopanib, which was complicated by severe hypertension requiring multiple anti-hypertensives. She was started on doxorubicin and olaratumab due to disease progression in November 2016. She had initial treatment response but demonstrated disease progression in July 2017, and she was started on ipilimumab (1 mg/kg) and nivolumab (3 mg/kg) every 4 weeks for four cycles followed by maintenance nivolumab (6 mg/kg) every 4 weeks. Her subcutaneous nodules decreased in response to treatment (Fig. ). In December 2017, she was admitted for progressive dyspnea on exertion, orthopnea, and lower extremity edema, with workup confirming new-onset acute systolic heart failure with ejection fraction 29%. Troponin peaked at 0.15, and coronary angiogram did not reveal any obstructive coronary disease. No delayed enhancement was seen on cardiac MRI. She was evaluated by cardiology, and given the lack of myocarditis or scar on MRI and prior significant anthracycline dose, cardiology favored anthracycline effect as etiology of her non-ischemic cardiomyopathy. She underwent diuresis and was started on carvedilol and lisinopril for optimal medical management of heart failure. Given her continued response to nivolumab, it was resumed January 2018 with the plan to continue until progression or unacceptable toxicity. Her cardiac function recovered to baseline by May 2018. As of July 2020, she has received 50 cycles of immunotherapy and remains on maintenance nivolumab with complete response.


A 42-year-old female patient came to dermatology clinic for the correction of facial hemiatrophy and hyperpigmentation on the right side of the face (, ). She suffered from progressive symptoms since 20 years ago. She complained of intermittent unilateral migraine and trigerminal neuralgia, but there were no bony or vascular abnormalities on imaging study. She showed normal teeth arrangement and visual acuity, and had no other systemic or congenital disorder. She had been relieving her neurologic pain with painkiller for over ten years. She also received Nd-Yag laser toning (1064 nm, 1.5 J/cm2) for 8 times to treat hyperpigmented lesion. However, she did not receive surgical flap or fat graft for facial atrophy.
We choose a mixed form of filler (Restylane SubQ® [Q-Med, Uppsala, Sweden]: Restylane Vital® [Q-Med]=2:1), composed of HA, for soft tissue augmentation. And we made two puncture sites with 22 gauge needle on the right cheek and mandibular area. After local anesthesia, HA Filler was injected via 23 gauge cannula pulling the needle back. A total of 7 ml of filler was used: 4 ml of HA filler was injected into the cheek, and the remaining 3 ml was injected into the mandibular area (, ). Because the adhesion between facial skin and subcutaneous fat was too tight to inject HA filler, we made a split space by subcision with a cannula before HA filler injection. A part of depressed area would need to be recontoured by second filler injection, however the patient was satisfied with cosmetic result and did not want to undergo another painful subcision. So we finished injecting further HA filler. It only took about 30 minutes for the procedure overall. One month after the first injection, additional 1.5 ml of HA filler was injected using fanning technique on the chin (, ). After 1 year later, additional therapy was done with 3 ml of HA filler, significant improvement of contour of left chin was seen (, ). Two months later, she did not show any signs of atrophy, and she was satisfied with the procedure. Also, there were no adverse events such as bruising, tenderness, overcorrection, chewing discomfort, Tyndall effect, the occlusion of the vessel or foreign body reaction.


A 14-year-old boy presented with a skin tag-like lesion on his right lower neck, and a red-colored papule on his right upper neck (). The lower lesion was asymptomatic and had been present since birth. The upper lesion developed 1 month ago and bled frequently. The patient had been otherwise healthy with no known prenatal or developmental abnormalities or significant family history. Physical examination revealed a soft, pedunculated, skin-colored papule, 3 mm in diameter, on the slightly elevated surface on the right lower neck (), and a soft, domeshaped, red-colored papule, 2 mm in diameter, on the right upper neck (). Under the clinical impressions of skin tag and pyogenic granuloma, respectively, punch excision was performed for each lesion. Histopathologically, the lower skin-colored papule demonstrated a polypoid skin segment with mild epidermal hyperplasia and many vellus hair follicles in the dermis (). Several sebaceous and eccrine glands connected with the hair follicle were also seen (), and perifollicular stroma showed fibrous thickening (). Serial sections did not reveal any cartilage, cystic follicular structures in the stroma, or prominent connective tissue framework in the subcutaneous fat. The upper red papule showed an exophytic lesion with lobular proliferation of capillaries, consistent with pyogenic granuloma. Based on the clinical and pathologic findings, diagnoses of HFN and pyogenic granuloma were made, respectively.
With CK19 (1:200, M0888; DAKO, Glostrup, Denmark) immunohistochemical stainining, follicular epithelium of some of the follicles in HFN and CCBR demonstrated positive expression (). In accessory tragus, virtually all hair follicles showed negative expression except for a few follicles which showed weak expression of CK19 focally (). In contrast, trichofolliculoma demonstrated no expression of CK19 in the hair follicles at all ().


A 13-year-old 40 kg male intact German Wirehaired Pointer was presented to a primary care clinic for evaluation of straining to defecate and urinate. Abdominal ultrasound examination was performed by the referring veterinarian, who diagnosed a pelvic cystic mass. Fine needle aspiration (FNA) was performed, resulting in a diagnosis of pyogranulomatous inflammation.
The dog was referred to the Veterinary Teaching Hospital of the Università degli Studi di Milano (Lodi, Italy) for a second opinion 15 days after initial presentation to the referring veterinarian. The dog had a 2-year history of prostatitis that had resolved with medical treatment.
On physical examination, body condition score was 4/9, and the dog had normal mentation, adequate hydration, pink mucosal membranes, and normal capillary refill time. The popliteal lymph nodes were enlarged, and rectal temperature was normal. Caudal abdominal palpation identified a firm intra-abdominal mass, and rectal examination confirmed the presence of a mass causing extraluminal compression of the rectum.
Abdominal radiography disclosed severe dilatation of the colon with granular fecal material indicative of megacolon, moderate urinary bladder distension, and the presence of increased soft tissue opacity in the region of the prostate gland protruding cranially from the pelvic inlet and associated with severe segmental compression of the rectum, thoracic radiography was unremarkable (Figure ). Abdominal ultrasound examination identified a multicavitary cystic mass, 9 × 6 cm in size, localized in the right pelvic region, adjacent to the prostate gland that had medium homogeneous echogenicity and smooth margins. The mass was causing compression and displacement of the rectum and urethra. No regional lymphadenopathy was detected (Figure ).
Ultrasound-guided FNA was performed percutaneously from the right perineal area, and 20 mL of reddish-brown fluid was obtained for cytological analysis, which was nondiagnostic.
Whole body computed tomography (CT) examination was performed under general anesthesia, which was induced using 4 mg/kg propofol (Propovet, Zoetis Italia Srl, Rome, Italy) and maintained with isoflurane in 100% oxygen (Isoflurane Vet, Merial, Lyon, France). Pre- and postcontrast examination was performed using a 16-slice CT scanner (Brightspeed, GE Healthcare, Milano, Italy). Computed tomography disclosed an ellipsoidal, well-defined multicavitary cystic mass, 48 × 53 × 70 mm in size, characterized by ring and heterogeneous contrast enhancement, with evidence of a thick enhancing wall, multiple septation, and distinctly marginated fluid-filled hypoattenuating cavities. The mass occupied up to 80% of the diameter of the pelvic canal on the transverse plane, with severe leftward compression of the rectum. The mass was located along the profile of the prostate gland, which was cranially displaced, but appeared within normal limits for size (18 × 32 × 35 mm) density and enhancement. No signs of abdominal or thoracic metastatic disease were identified. Differential diagnoses included prostatic mass (mesenchymal neoplasia, less likely prostatic or paraprostatic cyst or abscess), rectal wall exophytic neoplasia (eg, round cell tumor, carcinoma, less likely duplication cyst), and intrapelvic hemangiosarcoma. The day after CT, celiotomy with open subcapsular partial prostatectomy was scheduled.
The patient was sedated using dexmedetomidine 5 μg/kg IM (Dexdomitor, Vétoquinol Italia S.r.l., Bertinoro, Italy) and placed in dorsal recumbency. General anesthesia was induced using propofol 4 mg/kg (Propovet, Zoetis Italia S.r.l.) and maintained with isoflurane in 100% oxygen (Isoflurane Vet, Merial). The patient was catheterized and prepared for surgery.
A ventral midline celiotomy was performed, and a firm asymmetrical prostate gland, 9 cm in diameter, was observed. Large cysts were located along the dorsal prostatic profile adjacent to the colon. The cyst was drained of a brown liquid, and partial subcapsular prostatectomy was completed. The excised mass (Figure ) was immersed in 10% buffered formalin and submitted for histopathology. The dog was neutered during the procedure.
Grossly, a large, well-defined, nonencapsulated grayish mass with a central pseudocystic cavity was observed. Sections of the mass were processed for histology, and embedded in paraffin. Sections (5 μm) were cut and stained with hematoxylin and eosin. Additional sections were immunostained (using the standard Avidin-Biotin Complex [ABC] method). Histologically, the neoplastic mass consisted of long, dense, irregularly interlaced bundles of spindle cells, multifocally separated by edema, demarcating a large necrotic and cystic central area infiltrated by degenerate neutrophils. Neoplastic cells exhibited poorly defined cell borders, fusiform nuclei with finely reticulated chromatin and multiple (1-3) small nucleoli, and a moderate amount of intensely eosinophilic cytoplasm. Moderate anisokaryosis and anisocytosis were evident, and mitoses ranged from 0 to 3 per high power field (7 mitoses/2.37 mm2; Figure ). Intense hyperemia and neutrophilic and lymphoplasmacytic mild multifocal infiltration were observed in the fibro-adipose tissue at the periphery of the mass.
Serial microtome sections of the mass also were processed for immunohistochemistry, applying the standard ABC method and antibodies against alpha smooth muscle actin (ASMA; clone 1A4, 1:2000 dilution; Dakocytomation, Glostrup, Denmark), vimentin (clone 3B4; 1:1000 dilution; Dakocytomation), and desmin (clone DERII; 1:200 dilution; Novocastra Laboratories, Newcastle, United Kingdom). Neoplastic cells were immunostained intensely with ASMA and desmin (Figures and ), and they were mostly negative for vimentin. Histological and immunohistochemical results were consistent with a diagnosis of leiomyosarcoma, most likely originating from the muscular component of the prostatic capsule., ,
One month after surgery, follow-up with CBC, serum biochemistry, and abdominal ultrasound examination identified no abnormalities. At this time, the dog's owner consented to an adjuvant chemotherapy protocol using metronomic administration of cyclophosphamide at a dosage of 15 mg/m2 PO q24h (Endoxan, Baxter, Italy) and the nonsteroidal anti-inflammatory drug firocoxib at a dosage of 5 mg/kg PO q24h (Previcox, Merial). The protocol consisted of monthly follow-up evaluations including clinical observation, CBC, and serum biochemistry. At the second follow-up, mild increases in renal function tests were detected, but they remained within the reference range. Consequently, administration of firocoxib was changed to q48h.
At the 3-month follow-up, urinalysis and abdominal ultrasound examinations were normal. Whole body CT examination was repeated 10 months after surgery, and no signs of local recurrence or distant metastasis were evident (Figure ). The metronomic regimen was discontinued after 15 months because of a persistent increase in serum creatinine concentration (1.7 mg/dL) and blood urea nitrogen concentration (98 mg/dL). No signs of local progression or distant metastasis were present at clinical examination at this time.
To our knowledge, this case represents the first report of a dog with prostatic leiomyosarcoma that underwent surgery and chemotherapy, resulting in successful outcome. In the veterinary literature, only 2 cases of prostatic leiomyosarcoma in dogs have been reported. Patients with this uncommon condition were characterized by poor, or no follow-up.
The prostate gland in dogs is covered by a fibromuscular capsule. Smooth muscle cells spread from the wall of urinary bladder binding the prostate capsule. Capsular trabeculae divide each prostatic lobe into lobules, with a stroma consisting of collagen fibers, fibroblasts, and smooth muscle. The smooth muscle cells localized in the periphery of the prostate enable prostatic contraction. Leiomyoma is a rare benign tumor, and only 1 case has been reported in male dogs, whereas prostatic leiomyosarcoma is a malignant and aggressive neoplasm with only 2 cases reported in the literature.,
The dogs diagnosed with prostatic leiomyosarcoma in previous reports were 6 and 10 years old, and presented for evaluation of stranguria, dyschezia, and urinary incontinence. Diagnosis in previous cases was made using ultrasound-guided biopsy, prostatectomy, or necropsy. At the time of diagnosis, previously reported cases had metastasized to the lungs,, regional lymph nodes, mesentery, and kidneys.
No signs of vertebral metastasis have been identified in our patient or in the cases reported previously. The CT study in our case and necropsy in the previously reported cases did not show any vertebral involvement. This result may have been associated with the imaging technique limitations and none of the patients had other more sensitive and specific procedures for the detection of skeletal metastases performed. Other malignant prostatic tumors such as prostatic carcinoma are characterized by bone metastases, both in human beings and in dogs. One of the main sites of metastatic bone distribution in prostatic carcinoma is the axial skeleton, in particular the lumbosacral vertebre.
The reason for this metastatic pathway can be explained by Batson's plexus. This anatomical structure is a vertebral valveless network of veins, present both in humans and dogs. In dogs, the plexus system, also known as vertebral venous plexuses, is composed of internal and external components. Prostatic tumor cells may metastasize by this route forming metastatic tumors in the lumbar vertebrae via a low-pressure, high-volume system. This metastatic spread of cells is subjected to retrograde movement, following a pressure mass effect that may happen during defecation, coughing, or after changes in recumbency.
The origin and course of smooth muscle cells from the urinary bladder wall to the prostate capsule may be responsible for infiltration of the urinary bladder musculature, as reported in the literature. In our case, the prostatic neoplasia was exophytic, not infiltrating the surrounding structures, particularly the urethra and urinary bladder.
Diagnostic imaging features of prostatic leiomyosarcoma were described in a previous report. Ultrasonographic findings included a large heterogenous prostatic mass, characterized by a hyperechoic area surrounded by a hypoechoic band and the presence of large cystic lesions. The mass was reported to be hypoechoic compared to surrounding tissues after contrast medium injection. Computed tomography disclosed a large asymmetric and irregularly shaped prostate gland, heterogeneously attenuating, including large cystic areas. Contrast enhancement was minimal and heterogenous, with no enhancement of the cystic content. In a second case report, prostatic leiomyosarcoma was described radiographically as a caudal abdominal calcified mass. In both reports,, lung nodules were present, consistent with metastatic disease and, in 1 of the 2 cases, severe diffuse metastatic lymphadenopathy also was observed.
In our case, the pelvic mass was not mineralized and no extension into the surrounding structures or regional lymph nodes enlargement was observed, suggesting a probable benign nature of the mass. Moreover, lung metastases were not detected. On both ultrasonography and CT, the origin of the mass was not clear, but its exophytic distribution resembled that described in a former case report of prostatic leiomyoma, supporting the diagnosis of a benign mass. However, the previously reported prostatic leiomyoma appeared as a homogenous soft tissue attenuating mass with homogenous contrast enhancement on CT, whereas in our case some large cyst-like hypoattenuating areas with no contrast enhancement were present, as previously reported in prostatic leiomyosarcoma,, prostatic hemangiosarcoma, and malignant intrapelvic masses.,
In our case, despite the absence of metastatic disease and evidence of aggressive features typical of malignant neoplasms, necropsy identified a malignant neoplasm compatible with leiomyosarcoma. Moreover, the lack of prostatic calcification, which might be indicative of a chronic prostatitis or neoplasia such as adenocarcinoma, was absent in this case. Recently, features of lymphoma affecting the prostatic gland were reported on ultrasound examination with typical hypoechoic appearance associated with lymphadenopathy, which was not supported in our findings of a cystic mass without lymphadenopathy.
Because of the rarity of primary leiomyosarcoma, the therapeutic approach remains unclear, and multimodal treatment is recommended.
In our case, the patient underwent partial subcapsular prostatic resection. The decision to perform a partial prostatectomy was made to avoid pubic symphysiotomy in an older dog with severe degenerative disease of the coxofemoral joints. A standard ventral approach was used to avoid the main prostatic vessels, mitigate hemorrhage, and obtain a clear surgical field. Total prostatectomy has been associated with a high incidence of postoperative incontinence, but has yielded no increase in survival time in patients with prostatic diseases.
When chemotherapy was proposed, ifosfamide, cyclophosphamide, or dacarbazine have been the chemotherapeutic agents commonly selected in human medicine. Metronomic chemotherapy was reported to decrease cutaneous soft tissue sarcoma recurrence in dogs, but no data are available for visceral sarcomas. Adjuvant therapy options were discussed with the owner and metronomic chemotherapy was chosen with consideration of the patient's quality of life and owner compliance (ie, better tolerability and low cost).
No long-term follow-up was described in the clinical cases previously reported in the literature., One of the 2 cases was euthanized because of poor prognosis and the other died during hospitalization. As a particularly aggressive but rare cancer in veterinary medicine, information regarding clinical monitoring of these patients is lacking. The novelty of our case was the multimodal therapeutic approach and long postoperative follow-up, which ultimately yielded good outcome (survival 15 months after surgery, with no sign of distant metastases or local recurrence, based on CT; Figure ).
The main limitation of our study was the fact that it was only a single case, which reflects the rarity of this type of tumor in dogs. Multimodal treatment using partial subcapsular prostatectomy and adjuvant metronomic chemotherapy in an older patient with localized cancer therefore may be indicated in dogs presenting with cystic exophytic masses suggestive of prostatic leiomyosarcoma.


A 54-year-old Chinese male patient presented with a 4-year history of recurrent right lumbar aching pain. He had no medical history and no episodes of urgency, odynuria, or fever. Physical examination found no palpable abdominal mass or renal percussive pain. Contrast-enhanced abdominal computed tomography (CT) showed a space-occupying lesion with multiple enlarged lymph nodes in the right renal pelvis (). The left kidney, bowel, liver, pancreas, spleen, and both adrenals appeared normal. There were no abnormalities on chest CT. The results of routine blood tests and liver and kidney functions were also normal. Urine microscopy showed three to four red blood cells per high-power field. Detection of tumor markers was requested by the patient, and laboratory tests revealed high levels of serum CA19-9 (5163.12 U/mL) and CYFRA 21-1 (29.06 ng/mL). Other tumor markers, including carcinoembryonic antigen (CEA; 2.7 ng/mL), alpha-fetoprotein (AFP; 2.04 ng/mL), and CA72-4 (1.99 U/mL) were within normal ranges.
Laparoscopic right radical nephroureterectomy (RNU) was performed, and based on histopathological examination of the specimen, the renal pelvic tumor was diagnosed as a high-grade UC (pT3N0M0). Serum CA19-9 and CYFRA 21-1 levels had fallen to 1958.87 U/mL and 2.27 ng/mL, respectively, on the 3rd postoperative day. Serum CA19-9 levels were further decreased to 71.38, 28.85, 28.64, and 28.58 U/mL at 6 weeks, 10 weeks, 6 months, and 12 month postoperatively, respectively (). Postoperative serum CYFRA21-1 levels were repeatedly within the normal range (). There was no evidence of recurrence or metastasis on CT and cystoscopy for 12 months after surgery.


A 69-year-old Chinese female patient presented with a 10-day history of recurrent gross hematuria. Physical examination was non-informative. The patient had been healthy all her life and her family history was unremarkable. A contrast-enhanced CT scan of the abdomen and pelvis showed a heterogeneous enhancing mass arising from the lower pole of the left kidney, measuring 5.8 × 4×3.5 cm (). The right kidney, bowel, liver, pancreas, spleen, and both adrenals appeared normal, and there were no abnormal findings on chest CT. The results of routine blood tests and liver and kidney functions were normal. Gross hematuria was evident and urine microscopy showed 2922 red blood cells per high-power field. Tumor markers were detected at the patient’s request, and showed high levels of serum CA19-9 (176.422 U/mL) and CYFRA 21-1 (24.97 ng/mL). Other tumor markers, including CEA (2.66 ng/mL), AFP (2.84 ng/mL), CA72-4 (0.73 U/mL) CA12-5 (23.3 U/mL), and CA153 (16.0 U/mL) were within normal ranges.
Laparoscopic left RNU was performed and histopathological examination of the specimen led to a diagnosis of the renal pelvic tumor as high-grade UC (pT3N0M0). Serum CA19-9 and CYFRA 21-1 levels had fallen to 112.97 U/mL and 2.94 ng/mL, respectively, at 2 days post-surgery, and 47.61 U/mL and 3.05 ng/mL 1 week later. Serum CA19-9 was further decreased to 17.84 and 4.41 U/mL at 6 weeks and 6 months postoperatively, respectively). Serum CYFRA21-1 levels remained within the normal range (). There was no evidence of recurrence or metastasis on CT and cystoscopy at 6 months after surgery.


A 50-year-old male was referred to the Department of General Surgery at Jordan University Hospital, Amman, Jordan, complaining of right lower lip paresthesia and right facial pain radiating to the right ear of five-month duration. The patient was diagnosed in the private sector to have trigeminal neuralgia and was treated by Carbamazepine for two months. A month prior to admission, the patient started developing right facial swelling. Physical examination revealed right non-tender immobile parotid swelling without overlying skin changes. Trismus, right cervical and supraclavicular lymphadenopathy were also noted. There was no facial weakness. The patient has lost 20 kg over the last 2 months prior to admission.
Lab tests were performed and revealed hypercalcemia (calcium 12.20 mg/dL), hypoparathyroidism (PTH 5.6pg/mL), elevated aspartate aminotransferase (AST 110 u/lit) and lactate dehydrogenase (LDH 349 u/lit) were also noted.
Right parotid glandfine-needle aspirationcytology(FNA) was conducted twice due to inadequacy and showed multilayered sheets of cells with eccentric nuclei, granular cytoplasm, occasional prominent nucleoli and occasional mitotic figures, suspicious for malignancy. The cells were diffusely positive for CD-10 and AMACR with focal positivity for CK7. They were negative for C-kit immunostains. This immune profile favors RCC over the others.
Microscopically all the slides show a hemorrhagic smear containing scattered sheets and clusters of plasmacytoid and cuboidal cells having abundant cytoplasm and showing mild nuclear pleomorphism. The cytoplasm is granular and occasionally containing few vacuoles ().
A needle biopsy was done on the left renal mass and revealed Renal Cell Carcinoma with Furman nuclear grade (II/ III).A bone scan also revealed a suspicious lesion involving the right mandibular ramus, multiple bilateral pathologically enlarged supra and infraclavicular lymph nodes with necrotic center with the largest measured 2 cm in the short axis, enlarged subcarinal lymph nodes and bilateral hilar lymph node enlargement Large exophytic heterogeneously enhancing lobulated lesion with necrotic components occupying and distorting most of the upper and middle pole of the left kidney, were noticed (-).