A Rare Case of Other Iatrogenic Immunodeficiency-Associated Lymphoproliferative Disorders With Multiple Oral Mucosal Lesions During Methotrexate Therapy.

As of the most recent WHO classification of immunodeficiency diseases, lymphoproliferative disorders that occur during treatment with immunosuppressive drugs are classified as "other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPDs)" other than post-transplant lymphoproliferative disorders. Most patients with OIIA-LPD have rheumatoid arthritis as the underlying disease. Research indicates that approximately half of people diagnosed with OIIA-LPD see a remission of their lesion after stopping treatment with methotrexate (MTX), a drug used in rheumatoid arthritis treatment. Hereby, we present the case of an 81-year-old woman with rheumatoid arthritis who developed OIIA-LPD at the bilateral lingual margins. The patient had been receiving MTX for the preceding 10 years. After determining that OIIA-LPD was MTX-related, the patient underwent MTX withdrawal and was treated conservatively. The lesion resolved one month after MTX withdrawal. This case report confirms immunosuppressive drug withdrawal as a potentially effective treatment for multiple OIIA-LPDs of the oral mucosa.

A rare case of unilateral double Stafne bone defects and literature review.

Stafne bone defect (SBD) is a rare developmental bone defect characterized by an asymptomatic focal concavity of the cortical bone, typically on the lingual aspect of the mandibular body, which generally contains salivary gland tissue. It can be detected during routine dental examinations and typically appears as an ovoid, well-defined, well-corticated, radiolucent depression in the posterior mandibular region below the inferior alveolar nerve (IAN) (in: Neville et al, Oral and maxillofacial pathology, Elsevier, Inc, St. Louis, MO, 2016).An 80-year-old male presented to our clinic for a routine dental examination. Panoramic radiography and cone-beam computed tomography (CBCT) displayed two well-defined, well-corticated, ovoid radiolucencies inferior to the IAN canal on the left mandibular molar region. The working diagnosis was SBD, and the patient was informed of the findings. Irregular margins on the superior aspect of the anterior defect were noted on CBCT imaging; therefore, follow-up with panoramic images at 6 months, 1 and 5 years was recommended.

Optimization of collimator angle combined island blocking with parked gap achieves superior normal tissue sparing in SBRT planning of multiple liver lesions.

PURPOSE: To propose an efficient collimator angle optimization method by combining island blocking (IB) and parked gap (PG) problem to reduce the radiotherapy dose for normal tissue. The reduction will be done with single-isocenter multi-lesion volumetric modulated arc therapy (VMAT) for the stereotactic body radiation therapy (SBRT) of liver cancer. METHODS: A novel collimator angle optimization algorithm was developed based on the two-dimensional projection of targets on a beam's eye view (BEV) plane as a function of gantry and collimator angle. This optimization algorithm minimized the sum of the combined IB and PG (IB & PG) areas from all gantry angles for each arc. For comparison, two SBRT plans were respectively generated for each of the 20 retrospective liver cancer cases with multiple lesions. One plan was optimized using the IB & PG algorithm, and the other plan was optimized with a previously reported optimization algorithm that only considered the IB area. Plans were then evaluated and compared using typical dosimetric metrics. RESULTS: With the comparable target coverage, IB & PG plans had significantly lower D500cc, D700cc, mean dose (Dmean), and V15 of normal liver tissues when compared to IB plans. The median percent reductions were 3.32% to 5.36%. The D1cc, D5cc, and Dmean for duodenum and small intestine in IB & PG plans were significantly reduced in a range from 7.60% up to 16.03%. Similarly, the median integral dose was reduced by 3.73%. Furthermore, the percentage of normal liver Dmean sparing when IB & PG plans compared to IB plans, was found to be positively correlated (ρ = 0.669, P = 0.001) with the inter-target distance. CONCLUSION: The proposed IB & PG algorithm has been demonstrated to outperform the IB algorithm in almost all normal tissue sparing, and the magnitude of liver sparing was positively correlated with inter-target distance.

Multiple enteric muco-submucosal elongated polyps causing intussusception.

A 20-year-old woman presented to our hospital with abdominal pain. Abdominal computed tomography revealed multiple masses in the upper jejunum, which were suspected as lipomas. Partial resection of the small intestine, including the masses, was performed on the same day due to intussusception secondary to the masses. Pathological examination revealed that the masses consisted of mucosa and edematous submucosa with multiple dilated blood vessels and lymphatic ducts without muscularis propria. The masses were diagnosed as multiple muco-submucosal elongated polyps (MSEP), a type of non-neoplastic polyp. MSEP was originally named colonic MSEP, but with the development of endoscopic techniques and imaging tests, similar polyps have been reported to occur not only in the colon but also in the entire intestinal tract. In this case, multiple MSEPs in the upper jejunum caused intussusception. As reported cases of multiple lesions causing intussusception are few, our case may help to clarify the pathogenesis of this disease.

Extremely rare occurrence of multiple cranial fasciitis: A case report.

Cranial fasciitis (CF) is a rare, rapidly growing, benign fibroproliferative lesion of the skull in the pediatric population. It is characterized by benign mesenchymal proliferation of spindle cells arranged as short, intersecting loose fascicles within a fibromyxoid stroma, and mostly appears as a single mass. A surgical excision with clear surgical margins is definitively curative for CF. Up to date only two cases with multiple CF have been reported in the literature. In this report, we describe a 1-year-old girl with multiple locations of CF, as the first case to be reported in the Turkish population. The radiological and morphological findings of our case were comparable with the observations of the two previous reports in the literature. Histopathological examination remains to be the gold-standard for differential diagnosis of CF, as the treatment of this lesion differs from other malignancies of the skull in the pediatric population.

Simultaneous hemorrhage of multiple cerebral cavernous malformations of the insular lobe and Meckel's cave: a case report and literature review.

We describe a case of sporadic cavernous malformation (CM) in a patient suffering from multiple hemorrhagic intracranial lesions, including one originating from the trigeminal nerve (TN). The patient presented with left side facial pain and disturbed right limb movement. The patient was pre-operatively diagnosed with multiple cerebral CMs. This diagnosis was confirmed by postoperative pathology.

Spatial heterogeneity of infiltrating T cells in high-grade serous ovarian cancer revealed by multi-omics analysis.

Tumor-infiltrating lymphocytes (TILs), especially CD8+ TILs, represent a favorable prognostic factor in high-grade serous ovarian cancer (HGSOC) and other tumor lineages. Here, we analyze the spatial heterogeneity of different TIL subtypes in HGSOC. We integrated RNA sequencing, whole-genome sequencing, bulk T cell receptor (TCR) sequencing, as well as single-cell RNA/TCR sequencing to investigate the characteristics and differential composition of TILs across different HGSOC sites. Two immune "cold" patterns in ovarian cancer are identified: (1) ovarian lesions with low infiltration of mainly dysfunctional T cells and immunosuppressive Treg cells and (2) omental lesions infiltrated with non-tumor-specific bystander cells. Exhausted CD8 T cells that are preferentially enriched in ovarian tumors exhibit evidence for expansion and cytotoxic activity. Inherent tumor immune microenvironment characteristics appear to be the main contributor to the spatial differences in TIL status. The landscape of spatial heterogeneity of TILs may inform potential strategies for therapeutic manipulation in HGSOC.

A case of ALK-positive histiocytosis with multiple lesions in the unilateral breast: A case report.

INTRODUCTION AND IMPORTANCE: Primary ALK-positive histiocytosis of the breast is rare. Here, we report a case of ALK-positive histiocytosis with multiple unilateral breast lesions. CASE PRESENTATION: Our patient was a 38-year-old female with primary ALK-positive histiocytosis of the breast with multiple lesions. There were no lesions in other organs, and the patient was considered surgically resectable and underwent a left total mastectomy and sentinel lymph node biopsy. Histopathologically, there were at least three lesions in the left breast in upper inner quadrant (UIQ), upper quadrant (UQ), and upper outer quadrant (UOQ). All lesions showed spindle-shaped tumor cells that were positive for CD163 and ALK and negative for AE1/AE3. Fluorescence in situ hybridization (FISH) showed ALK and KIF5B rearrangements, suggesting the presence of the KIF5B-ALK fusion gene. In conclusion, this case was confirmed to be ALK-positive histiocytosis with multiple lesions in the unilateral breast. The patient underwent surgery and was discharged without complications. CLINICAL DISCUSSION: Reports of ALK-positive histiocytosis are very rare, and reports of primary cases in the breast are even rarer. The basic treatment for ALK-positive histiocytosis is surgical resection; however, ALK inhibitors may be effective in unresectable or disseminated cases. Accurate diagnosis at the time of initial treatment is necessary to expand the treatment options. CONCLUSION: This is the first case of ALK-positive histiocytosis with multiple lesions in the unilateral breast.

Case Report: Stroke Chameleon: Acute Large Vessel Occlusion in the Posterior Circulation With Paroxysmal Sympathetic Hyperactivity as the First Manifestation.

Paroxysmal sympathetic hyperactivity (PSH) is a neurological emergency mostly secondary to traumatic brain injury (TBI). Acute large vessel occlusion (LVO) in the posterior circulation with PSH as the initial manifestation is uncommon. It may lead to catastrophic consequences for patients if not detected and treated timely. Here, we present three patients with acute LVO in the posterior circulation with PSH as the initial symptom. All patients were male and averaged 63 years old. The PSH Assessment Measure (PSH-AM) scores of all cases were > 17. Brain imaging showed that multiple lesions in posterior circulation were involved in three patients. Although the prognosis of all patients was poor, PSH symptoms disappeared in all patients after endovascular treatment. These cases suggests that acute posterior circulation-related ischemic stroke should be considered with PSH occurring as the first symptom. Extensive disconnection due to multiple lesions in posterior circulation may play an important role in the occurrence and development of PSH. Endovascular treatment may be effective for PSH caused by acute posterior circulation-related ischemic stroke. This is worthy of further study in the future.

LLRHNet: Multiple Lesions Segmentation Using Local-Long Range Features.

The encoder-decoder-based deep convolutional neural networks (CNNs) have made great improvements in medical image segmentation tasks. However, due to the inherent locality of convolution, CNNs generally are demonstrated to have limitations in obtaining features across layers and long-range features from the medical image. In this study, we develop a local-long range hybrid features network (LLRHNet), which inherits the merits of the iterative aggregation mechanism and the transformer technology, as a medical image segmentation model. LLRHNet adopts encoder-decoder architecture as the backbone which iteratively aggregates the projection and up-sampling to fuse local low-high resolution features across isolated layers. The transformer adopts the multi-head self-attention mechanism to extract long-range features from the tokenized image patches and fuses these features with the local-range features extracted by down-sampling operation in the backbone network. These hybrid features are used to assist the cascaded up-sampling operations to local the position of the target tissues. LLRHNet is evaluated on two multiple lesions medical image data sets, including a public liver-related segmentation data set (3DIRCADb) and an in-house stroke and white matter hyperintensity (SWMH) segmentation data set. Experimental results denote that LLRHNet achieves state-of-the-art performance on both data sets.

Specific Features of Patients Under 40 Years Old With Small-to-Medium-Sized Arterial Deterioration.

Background: Arterial deterioration is mostly caused by atherosclerosis, which progresses with age. However, we have observed serious backgrounds or etiologies in younger patients with non-atherosclerotic diseases and deterioration of small-to-medium-sized arterial lesions. Therefore, we aimed to identify the specific features of patients aged <40 years with deterioration of small-to-medium-sized arteries. Methods: We selected patients who were admitted to our department from 1995 to 2019 with deterioration of small-to-medium-sized arteries (aneurysms, dissection, rupture, or arterial injury/damage) and focused on the cohort aged <40 years. We examined the backgrounds or etiologies of the patients including genetic and inflammatory diseases, which might have caused the arterial deterioration. Results: Consequently, more than half (54.1%) of the patients aged <40 years had non-atherosclerotic comorbid diseases. However, the number of deteriorated arterial lesions was higher in patients aged <40 years than in patients aged ≥40 years (3.13 vs. 1.33 lesion/patient; P = 0.011). Furthermore, the data analysis of patients with multiple arterial lesions (≥3) revealed that the younger population tended to have more specific backgrounds or etiologies, notably Ehlers-Danlos syndrome and Behçet's disease. There were no differences in the all-cause mortality and cardiovascular disease-related mortality between patients aged <40 and ≥40 years (P = 0.89 and 0.29, respectively). Conclusions: Over 50% of patients aged <40 years with deterioration of small-to-medium-sized arteries had non-atherosclerotic, specific clinical backgrounds or etiologies, including genetic and inflammatory diseases. In addition, they exhibited more arterial lesions than older patients.

Lesion Heterogeneity and Long-Term Heteroresistance in Multidrug-Resistant Tuberculosis.

Tuberculosis heteroresistance, in which only a fraction of the bacteria in a patient with tuberculosis contains drug-resistant mutations, has been a rising concern. However, its origins and prevalence remain elusive. Here, whole-genome sequencing was performed on 83 serial isolates from 31 patients with multidrug-resistant tuberculosis, and heteroresistance was detected in isolates from 21 patients (67.74%). Heteroresistance persisted in the host for long periods, spanning months to years, and was associated with having multiple tubercular lesions. Our findings indicate that heteroresistance is common and persistent in patients with multidrug-resistant tuberculosis and may affect the success of their treatment regimens.

A novel restricted single-isocenter stereotactic body radiotherapy (RESIST) method for synchronous multiple lung lesions to minimize setup uncertainties.

Treating multiple lung lesions synchronously using a single-isocenter volumetric modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) plan can improve treatment efficiency and patient compliance. However, due to set up uncertainty, aligning multiple lung tumors on a single daily cone beam CT (CBCT) image has shown clinically unacceptable loss of target(s) coverage. Herein, we propose a Restricted Single-Isocenter Stereotactic Body Radiotherapy (RESIST), an alternative treatment that mitigates patient setup uncertainties. Twenty-one patients with two lung lesions were treated with single-isocenter VMAT-SBRT using a 6MV-FFF beam to 54 Gy in 3 fractions (n = 7) or 50 Gy in 5 fractions (n = 14) prescribed to 70-80% isodose line. To minimize setup uncertainties, each plan was re-planned using the RESIST method, utilizing a single-isocenter placed at the patient's mediastinum. It allows for an individual plan to be created for each tumor, using the first plan as the base-dose for the second plan, while still allowing both tumors to be treated in the same session. The technique uses novel features in Eclipse, including dynamic conformal arc (DCA)-based dose and aperture shape controller before each VMAT optimization. RESIST plans provided better target dose conformity (p < 0.001) and gradient indices (p < 0.001) and lower dose to adjacent critical organs. Using RESIST to treat synchronous lung lesions with VMAT-SBRT significantly reduces plan complexity as demonstrated by smaller beam modulation factors (p < 0.001), without unreasonably increasing treatment time. RESIST reduces the chance of a geometric miss due by allowing CBCT matching of one tumor at a time. Placement of isocenter at the mediastinum avoids potential patient/gantry collisions, provides greater flexibility of noncoplanar arcs and eliminates the need for multiple couch movements during CBCT imaging. Efficacy of RESIST has been demonstrated for two lesions and can potentially be used for more lesions. Clinical implementation of this technique is ongoing.

The characteristics and prognostic significance of esophageal squamous cell carcinoma with synchronous multiple lesions: over 10-year experience.

PURPOSE: Esophageal squamous cell carcinoma (ESCC) is occasionally observed with synchronous multiple tumor lesions. Our study is aiming to define the clinical and prognostic features of this pathological subtype. METHODS: This study included a large cohort of 1126 ESCC patients received esophagectomy with systemic lymph-node dissection between 2003 and 2013 in Sun Yat-sen University Cancer Center. The characteristics and prognostic significance of ESCC with multiple lesions were analyzed. The propensity score matching was performed to balance the baseline clinical characteristics. RESULTS: A total of 103 patients (9.1%) with 216 synchronous multiple lesions were identified from postoperative gross samples. Among them, 94 patients had two lesions, and 8 patients had three lesions, while only one patient had four lesions. The consistency of pT stages and histological grade among tumor lesions from the same gross sample were 19.4% (20/103) and 37.9% (39/103), respectively. Additionally, the tumor sites, sizes, and even the pathological subtypes can be variant in one patient. The preoperative upper gastrointestinal endoscopy could only identified 80.1% of the multiple tumor lesions. The male gender (P = 0.012), positive personal cancer history (P < 0.001), and higher pN stages (P < 0.001) were independent risk factors for synchronous multiple lesions. Patients with multiple lesions showed significantly lower survival rate (P = 0.002), and the multiple-lesion was an independently adverse prognostic factor in operable ESCC (P = 0.002). CONCLUSION: ESCC with multiple lesions had unique clinical features and should not be simply treated as the one-lesion ESCC. Due to its worse prognostic impact, advanced multidisciplinary therapies should be considered for patients with multiple esophageal tumor lesions.

Automation and integration of a novel restricted single-isocenter stereotactic body radiotherapy (a-RESIST) method for synchronous two lung lesions.

Synchronous treatment of two lung lesions using a single-isocenter volumetric modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) plan can decrease treatment time and reduce the impact of intrafraction motion. However, alignment of both lesions on a single cone beam CT (CBCT) can prove difficult and may lead to setup errors and unacceptable target coverage loss. A Restricted Single-Isocenter Stereotactic Body Radiotherapy (RESIST) method was created to minimize setup uncertainties and provide treatment delivery flexibility. RESIST utilizes a single-isocenter placed at patient's midline and allows both lesions to be planned separately but treated in the same session. Herein is described a process of automation of this novel RESIST method. Automation of RESIST significantly reduced treatment planning time while maintaining the benefits of RESIST. To demonstrate feasibility, ten patients with two lung lesions previously treated with a single-isocenter clinical VMAT plan were replanned manually with RESIST (m-RESIST) and with automated RESIST (a-RESIST). a-RESIST method automatically sets isocenter, creates beam geometry, chooses appropriate dose calculation algorithms, and performs VMAT optimization using an in-house trained knowledge-based planning model for lung SBRT. Both m-RESIST and a-RESIST showed lower dose to normal tissues compared to manually planned clinical VMAT although a-RESIST provided slightly inferior, but still clinically acceptable, dose conformity and gradient indices. However, a-RESIST significantly reduced the treatment planning time to less than 20 min and provided a higher dose to the lung tumors. The a-RESIST method provides guidance for inexperienced planners by standardizing beam geometry and plan optimization using DVH estimates. It produces clinically acceptable two lesions VMAT lung SBRT plans efficiently. We have further validated a-RESIST on phantom measurement and independent pretreatment dose verification of another four selected 2-lesions lung SBRT patients and implemented clinically. Further development of a-RESIST for more than two lung lesions and refining this approach for extracranial oligometastastic abdominal/pelvic SBRT, including development of automated simulated collision detection algorithm, merits future investigation.

Multiple extensive Madurella mycetomatis eumycetoma lesions: a case report and review of the literature.

In this communication, we report on the first-ever patient presenting with 17 lesions of Madurella mycetomatis eumycetoma in different parts of the body. The reported patient is a 15-y-old female who presented to the Mycetoma Research Centre, University of Khartoum, Khartoum, Sudan, in 2017 with recurrent back and anterior abdominal wall eumycetoma lesions. They were surgically excised, and during the course of follow-up, she developed 15 other eumycetoma lesions, scattered mostly on her upper and lower limbs and gluteal region. The diagnosis of Madurella mycetomatis was confirmed by molecular identification of grains and culture, histopathological examination and ultrasound examination. The cause and the explanation of such a presentation in puzzling; it is not due to multiple subcutaneous implantations because of the lack of history of relevant local trauma. Lymphatic spread is unlikely as the distribution of the lesions is not in line with this. Haematogenous spread is a possible explanation. This rare presentation of eumycetoma poses a great challenge for diagnosis and management.

Clinical analysis of 117 cases with synchronous multiple primary esophageal squamous cell carcinomas.

BACKGROUND/AIMS: We aimed to study the clinical characteristics, treatment modality, and the prognosis of synchronous multiple primary esophageal squamous cell carcinomas (SMPESCC). METHODS: A total of 117 SMPESCC cases were evaluated retrospectively from 2010 to 2015. RESULTS: The most common locations of SMPESCC were mid- and lower thoracic segments (n = 208, 84.9%). The 1-, 2-, and 3-year overall survival rates were 53.8%, 30.8%, and 15.4%, respectively; the median survival time (MST) was 12.5 months. With definitive radiotherapy and surgery, respectively, the MST of stage I/II patients were 34.2 and 26.7 months, of stage III patients were 8.3 and 13.2 months (p = 0.163), and of stage IV patients were and 8 and 12.6 months (p = 0.379). Clinical stage, family history of cancer, and Karnofsky performance status were independent prognostic factors for the whole cohort by Cox multivariate regression analysis (hazard ratio [HR] = 0.859, p < 0.001; HR = 0.579, p = 0.032; and HR = 0.586, p = 0.013). CONCLUSION: Although the prognosis of SMPESCC is poor, stage I/II patients can achieve long-term survival with aggressive treatment, especially those with a Karnofsky performance score 90 or higher and who have no family history of cancer. Definitive radiotherapy could achieve a similar survival rate to definitive surgery at different clinical stages.

Benefit of dosimetry distribution for patients with multiple brain metastases from non-small cell lung cancer by a Cyberknife stereotactic radiosurgery (SRS) system.

BACKGROUND: In order to obtain a high dose conformal index of tumor and steep dose fall-off in healthy tissues for brain metastasis stereotactic radiosurgery (SRS), the aim of this study was to investigate SRS planning optimization by comparing one multiple-lesions plan (MLP) with multiple single-lesion plans (SLPs) for patients with multiple brain metastases using the Cyberknife (CK) system. METHODS: Fifty non-small cell lung cancer (NSCLC) patients (28 males and 22 females) with 2-4 brain metastases, inter-tumour distances less than 3 cm, were retrospectively replanned with the original prescription dose (12-32 Gy) in the original fractions (1-3). Two different clinical CK SRS plans (SLPs and MLP) were generated for the same patients with the same collimator and prescription isodose line (62-68%) by the CK Multiplan System. Both SLPs and MLP were able to achieve > 95% PTV volume covered prescription dose and met the Timmerman 2011 organs at risk (brainstem, optic nerve and pituitary) constraints. RESULTS: Compared with those in the SLPs, the maximum dose (Dmax) and mean dose (Dmean) of brainstem in the MLP were reduced 0.22-3.13% (2.62%) and 2.71-12.56% (5.57%), respectively, all P < 0.05. Meanwhile, the volumes of the whole brain minus the tumors that received a single dose equivalent of 8-16 Gy (V8Gy-V16Gy) were effectively reduced in the MLP. The treatment time parameters, the total number of beams and monitor units, of the MLP were reduced by 3.31 and 1.47% (P < 0.05), respectively. Although there were a few differences in the conformity index (CI) and homogeneity index (HI) between the two treatment plans, the differences were not statistically significant (P = 2.94 and 1.08 > 0.05). CONCLUSION: One multiple-lesions plan for brain metastases could achieve higher precision in the target and lower doses in healthy tissue while shortening the treatment time and improving the treatment efficiency over multiple single-lesion plans.

How to Treat Multifocal Ta High-grade Disease if Bacillus Calmette-Guérin Is Unavailable.

A 71-yr-old man was transferred to our institution with multiple and recurrent high-grade pTa bladder cancer 26mo after an initial presentation of multiple and large pTa low-grade tumors and concomitant carcinoma in situ, treated with transurethral resection plus 6-mo postoperative mitomycin C. This case discusses several treatment options in the absence of bacillus Calmette-Guérin (BCG). Immediate radical cystectomy is an option with excellent survival, since there is a substantial risk of understaging and disease progression; however, this results in overtreatment in ∼50% of these patients. Therefore, a conservative approach could be intravesical combination therapy such as gemcitabine/docetaxel or epirubicin/interferon. In addition, device-assisted intravesical therapy is becoming an option to consider. Finally, patients could be included in trials such as immunotherapy trials. PATIENT SUMMARY: This 71-yr-old patient was diagnosed with recurrent, moderately severe noninvasive bladder tumors, which were removed. The recommended additional therapy, intravesical bacillus Calmette-Guérin (BCG) instillations, was not available. Both the pros and the cons of radical surgery (bladder removal) and a more conservative approach (other intravesical treatments) are discussed.