Low-grade Malignancy Research Articles

The Bendamustine Plus Rituximab Regimen Is Active and Safe in Previously Untreated Patients with Waldenström Macroglobulinemia, a Study on Behalf of the French Innovative Leukemia Organization (FILO)

BackgroundWaldenström macroglobulinemia (WM) is a rare low-grade B-cell malignancy characterized by the infiltration of IgM-secreting lymphoplasmacytic cells in the bone marrow. There is no standard therapy for WM, but several drugs have been shown to be effective either alone or in combination. Bendamustine (B)-Rituximab (R) has been found to be effective in salvage (Tedeschi , Leukemia Lymphoma 2015) or first setting in MW (Treon, ASH2016).BR- regimen has however reported to be associated with an increase in secondary cancer and the development of secondary myelodysplastic syndrome (MDS) or acute myeloblastic leukemia (AML) in patients with previously treated non-Hodgkin lymphoma. Prolonged neutropenia after R-chemotherapy treatment of lymphoma or CLL has also been associated with an increase of MDS/AML, and a shorter interval between the occurrence of the two malignancies. However, this has not been evaluated in previously untreated WM, nor the possible relationship with secondary cytopenia to WM treatment.MethodsForty-four symptomatic previously untreated patients with WM based on the second WM Workshop recommendations for diagnostic criteria were enrolled in this retrospective multi-center study between January 2012 and January 2017 in ten French centers. MYD88L265P and CXCR4 mutations were searched using q PCR and or next generation sequencing. Del (17) p and/ or TP53 mutation were investigated for 22 patients. All patients received a BR regimen consisting of 375 mg/m2 of rituximab on day 1 and 90 mg/m2 of bendamustine on days 1 and 2, repeated every 4 weeks, with a maximum of 6 cycles. Long-term complications of BR, 6 months or more after treatment discontinuation were analyzed. PFS and OS were plotted using the log rank test and Kaplan-Meier comparison.ResultsThe median age at WM diagnosis was 69 years old (range 45-88) and the median age at initiation of therapy was 70 years old (range 46-89). The MYD88L265Pmutation was present in 24/30 (80%) of the cases. CXCR4 mutations were observed in 2/14 cases, alteration of TP53 in 1/22 cases.The median time from diagnosis to therapy was 2 months (range 0-123 months). The median serum IgM level was 3,870mg/dl (range 650-12000). The criteria for initiating BR treatment were: anemia (54%), B-symptoms (45%), hyper viscosity (25%), adenopathy and/or splenomegaly (18%), thrombocytopenia (16%), neuropathy (11%), and amyloidosis (4%). According to the IPSSMW score, 22% of patients were low risk, 35% intermediate risk, and 43% high risk. Overall 82% of patients completed the planned 6 courses.Using consensus response criteria, the ORR was 95% (CR15%, VGPR 40% PR38% MR 2%) and the major response rate (CR+VGPR+PR) 93%.Toxicities attributed to BR led to dose reduction and/ or incomplete regimen of intended therapy in 18% of patients. Their median age was 78 years old. Toxicities were related to excessive or prolonged myelosuppression in 5 patients and infection in 3.Most of the adverse events were hematological and infectious toxic effects. Grade 3-4 neutropenia occurred in 4 (11%) cases and grade 3-4 thrombocytopenia in one (3%). Minor infections developed in eight cases: three cutaneous infections, two herpes zosters, one upper respiratory tract infection, one sinusitis, and one oral-herpes. Grade 3-4 pneumonia was observed in two cases and sepsis in one.Among 38 evaluable patients for toxicities after BR therapy, 16(42%) developed one or more long-lasting cytopenias: neutropenia (34%), anemia (10%), and thrombocytopenia (8%), all grade I and II.The median duration for prolonged neutropenia, anemia, and thrombocytopenia were 6 months (range: 6-24 months), 7.5 months (range: 6-9 months) and 12 months (6-30 months), respectively.After a median observation time of 27 months (range 5-51 months) after BR-regimen, the PFS and OS were 92% and 100%, respectively. Two patients relapsed at 24 and 45 months. One patient with a history of breast cancer prior to WM treatment relapsed from this solid tumor at 23 months. None of the patients developed aggressive lymphoma or secondary MDS/AML at the last follow-up.ConclusionThe BR regimen is efficient in patients with previously untreated WM. In elderly patients, the dose of bendamustine needs to be lowered. Long-lasting cytopenia occurred in half of patients and resolved in most cases within one year after the end of treatment. Longer follow-up is needed to assess the long-term risks of BR treatment. DisclosuresLaribi:MUNDIPHARMA: Research Funding; NOVARTIS: Honoraria, Research Funding; ROCHE: Research Funding; TEVA: Research Funding; HOSPIRA: Research Funding; AMGEN: Honoraria; TAKEDA: Honoraria, Research Funding. Leblond:SERVIER: Honoraria, Membership on an entity's Board of Directors or advisory committees; GILEAD: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; JANSSEN: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria; ABBVIE: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ROCHE: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; NOVARTIS: Honoraria, Membership on an entity's Board of Directors or advisory committees.

The struggle against endometrial cancer: ten years of experience of a tertiary center.

We aimed to investigate the clinical and pathological factors of our patients who were diagnosed with endometrial cancer in terms of prognosis. With this study, we present our 10 years of surgical experience in endometrial carcinoma cases. Four hundred twelve patients with endometrial carcinoma who applied to our center between 2010-2019 and that we followed up were evaluated retrospectively. Most of the tumors were low-grade endometrioid malignancies. Non-endometrioid types accounted for 12.1% of cases. Lymph node dissection was performed in 395 of 412 patients (95.9%). 66 (16.01%) of the 412 patients died during the follow-up period in the study sample. Higher OS and DFS rates were associated with endometrioid histological types, FIGO stage, absence of lymphovascular space invasion, lower grade and less than 50% myometrial invasion (p < 0.05). 5-year OS at stage 1, 2, 3, 4 was found as 88.9 ± 2.2%, 65.5 ± 10.8%, 49.4 ± 0.79% and 23.7 ± 0.97% respectively. 5-year DFS at stage 1, 2, 3, 4 was found as 84.1 ± 2.6%, 65.5 ± 10.8%, 47.7 ± 0.78% and 23.7 ± 0.97% respectively. In univariate analysis, Age, tumor histology, FIGO stage, histological grade, LVSI, positive peritoneal cytology, cervical involvement, myometrial invasion and not receiving adjuvant therapy were defined as prognostic factors. Age, grade, FIGO stage, myometrial invasion, histological type, LVSI involvement, cervical involvemet, positive peritoneal cytology and not receiving adjuvant therapy are important prognostic factors for progression-free survival and overall survival in patients diagnosed with endometrial cancer.

INTRAOSSEOUS EPITHELIOID HAEMANGIOENDOTHELIOMA OF THE MANDIBLE

Case A fit and well 25-year-old man presented with worsening pain and bony swelling on the lingual aspect of the right premolar region. Radiology showed a multiloculated radiolucent lesion of the anterior mandible with bone expansion and displacement of roots. Initial biopsy revealed fragments of nested epithelioid tumor within the marrow space with extravasated red blood cells and hemosiderin suggestive of vascular origin. Further biopsy showed histologic features of epithelioid haemangioendothelioma (eHAE). Samples were sent to the National Orthopaedic Hospital for molecular testing but this was inconclusive, likely owing to formic acid decalcification. MDT decision for surgical resection was carried out with primary reconstruction. Histology from the resection revealed complete excision of eHAE with focal erosion through the buccal cortex. The patient has recovered well, and to date there is no evidence of recurrence. Discussion eHAE is a very rare vascular tumor of low-grade malignancy, which presents within the lung, liver, or bone including of the head and neck region with 4 cases reported within the mandible. Despite characteristic morphology, diagnosis can be challenging because of small sample size and the rarity of diagnosis. eHAEs are characterized by a WWTR1-CAMTA1 fusion with a minority also showing a YAP1-TFE3 fusion, however decalcification in formic acid can prevent adequate molecular analysis. Conclusions eHAE is a rare tumor with characteristic histologic features and potential for recurrence and metastasis. Molecular testing can assist diagnosis, and development of local tissue pathways for intraosseous tumors that facilitate molecular testing is essential for prompt diagnosis.

Dermoscopy of Dermatofibrosarcoma Protuberans

ermatofibrosarcoma protuberans (DFSP), also known as dermatofibrosarcoma of Darier and Ferrand, is a soft-tissue neoplasm of intermediate to low-grade malignancy, which accounts for 0.1–1% of all cutaneous malignant tumours [1]. The diagnosis of this entity is based on physical examination and a confirmative biopsy sample [2-5]. However, the lack of reliable clinical criteria suggestive of DFSP results in delayed diagnosis and poorer patient outcome.

Childhood-onset Craniopharyngioma.

Craniopharyngiomas are rare embryonic malformational tumors of the sellar/parasellar region, classified by the World Health Organization (WHO) as tumors with low-grade malignancy (WHO I). The childhood adamantinomatous subtype of craniopharyngioma is usually cystic with calcified areas. At the time of diagnosis, hypothalamic/pituitary deficits, visual disturbances, and increased intracranial pressure are major symptoms. The treatment of choice in case of favorable tumor location (without hypothalamic involvement) is complete resection. It is important to ensure that optical and hypothalamic functionality are preserved. In case of unfavorable tumor location, that is with hypothalamic involvement, a hypothalamus-sparing surgical strategy with subsequent local irradiation of residual tumor is recommended. In the further course of the disease, recurrences and progression often occur. Nevertheless, overall survival rates are high at 92%. Severe impairment of quality of life and comorbidities such as metabolic syndrome, hypothalamic obesity, and neurological consequences can be observed in patients with disease- and/or treatment-related lesions of hypothalamic structures. Childhood-onset craniopharyngioma frequently manifests as a chronic disease so that patients require lifelong, continuous care by experienced multidisciplinary teams to manage clinical and quality of life consequences. For this review, a search for original articles and reviews published between 1986 and 2020 was performed in Pubmed, Science Citation Index Expanded, EMBASE, and Scopus. The search terms used were "craniopharyngioma, hypothalamus, pituitary obesity, irradiation, neurosurgery.

Utility of Insulinoma-Associated Protein 1 (INSM1) and Mucin 2 (MUC2) Immunohistochemistry in the Distinction of Endocrine Mucin-Producing Sweat Gland Carcinoma From Morphologic Mimics.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare low-grade adnexal malignancy with a predilection for the eyelids of elderly White women, which is associated with invasive mucinous carcinoma with endocrine features in one-third of cases. EMPSGC is characterized by the presence of neuroendocrine differentiation and mucin production. However, EMPSGC displays a variety of architectural patterns including solid, cribriform, papillary, and cystic growth. In addition, EMPSGC may also display nonendocrine cytologic features, such as apocrine change. Because of their variable appearance, EMPSGC can show significant morphologic overlap with certain histologic mimics, namely basal cell carcinoma, hidrocystoma, apocrine hidradenoma, and tubular adenoma. In addition, the often limited sampling of this anatomically delicate area can make the diagnosis of EMPSGC challenging. EMPSGC expresses neuroendocrine markers, including synaptophysin and chromogranin, often in a focal distribution. However, insulinoma-associated protein 1 (INSM1) has been found to be a more sensitive marker for EMPSGC. Recent studies have also demonstrated the expression of the gel-forming mucin 2 (MUC2) in EMPSGC, possibly signifying a lacrimal or conjunctival origin of these neoplasms. In this article, we discuss EMPSGC in the context of its histologic mimics (BCC, hidrocystoma, apocrine hidradenoma, and tubular adenoma) and we investigate the utility of the immunohistochemical expression of INSM1 and MUC2 in the distinction of EMPSGC from them. We demonstrate that INSM1 and MUC2 can reliably distinguish EMPSGC from these histologic mimics.

When an old pigmented lesion becomes serious: the problematic diagnosis of low-grade skin malignancies – Bednar tumor with fibrosarcomatous transformation

Abstract Bednar tumor is a rare cutaneous neoplasm, regarded as a variant of dermatofibrosarcoma protuberans with melanotic colonization and it usually affects young and middle-aged adults or children. This lesion is considered a low-grade malignant tumor, which can be associated with multiple local recurrences after surgical excision. Although a rare phenomenon, these lesions may undergo fibrosarcomatous transformation, which implies a poorer prognosis of the disease, as the tumor has a more locally aggressive behavior and patients might also develop distant metastases. We present the case of a 53-year-old female patient, with no significant medical history, who presented with a subcutaneous nodule on her upper back, for which a wide surgical excision was performed. The gross examination of the specimen showed a solitary protuberant grey-white nodule with a bluish shade and flecked with pigment. The microscopic examination revealed a malignant proliferation with a predominantly fascicular growth pattern, composed of spindle cells with highly pleomorphic nuclei and high mitotic rate, as well as the presence of dendritic cells with abundant melanin. Upon immunohistochemical analysis, the proliferation showed negative staining for CD 34 and AE 1/3, whereas the scattered dendritic cells stained positive with S100 protein. Ki 67 was positive in 15% of the tumor cells and the absence of p53 expression was noted. Thus, the diagnosis of Bednar tumor with fibrosarcomatous transformation was established. The aim of this paper was to gain further knowledge about the histopathological and immunohistochemical features, as well as about the treatment of Bednar tumor, especially considering its rarity.

Olfactory Preservation in Craniofacial Resection of Tumor Invading Hemianterior Skull Base: Operative Video.

In traditional craniofacial resection of tumors invading the anterior skull base, the bilateral olfactory apparatus is resected. Recently, transnasal endoscopy has been used for olfactory preservation in resections of unilateral low-grade malignancies. However, for tumors that invade the orbita or for high-grade malignancies, the transnasal endoscopic skull base surgery has been controversial. This video demonstrates the surgical techniques of olfactory preservation during craniofacial resection of a high-grade malignancy invading the hemianterior skull base and orbita. We present the case of a 32-year-old woman with osteosarcoma in the right ethmoid sinus. The tumor invaded the ipsilateral cribriform plate, dura menta, and orbital periosteum; however, the nasal septum and crista galli were intact ( Fig. 1A, B ). Because the tumor was a high-grade malignancy and the orbita had been invaded, we performed craniofacial resection instead of endoscopic resection ( Fig. C2A ). We drilled into the right side of the crista galli, midline of the cribriform plate, and perpendicular plate of the ethmoid bone via craniotomy. As a result, we accessed the nasal cavity directly ( Fig. 2B ). To preserve the nasal septum, we detached the remaining right septal mucosa through the transfacial approach ( Fig. 2C ). Because of the high risk of cerebrospinal fluid leakage as a result of previous irradiation, we performed vascularized free flap reconstruction of the skull base instead of pericranial flap. Postoperative computed tomography revealed no evidence of tumor ( Fig. 1C, D ). The patient's sense of smell returned after 1 postoperative day, and she was discharged on the postoperative day 14. The link to the video can be found at: https://youtu.be/XzPABYwzkjs .

Ocular surface squamous neoplasia at a tertiary eye facility, Southwestern Nigeria: a 10-year review

Ocular surface squamous neoplasia (OSSN) is a low-grade malignancy arising from the squamous epithelium of the ocular surface AIM: To describe the clinical presentation, histological diagnoses, treatment, and outcome of treatment in patients with OSSN managed at a tertiary health facility. Medical records of all patients with OSSN managed using a standardized treatment protocol over a 10-year period were reviewed. Eighty-six patients comprising 44 (51.2%) males and mean age of 48.2 ± 15.8years were studied. The most common presentation was a fleshy growth in the eye in all patients, and 43 (50.0%) patients tested positive to human immunodeficiency virus. The right eye was affected in 44 (51.2%) patients with no bilateral tumors, and the medial limbus was involved in 28 (32.6%) patients. Morphologically, 40 (46.5%) patients had gelatinous growth, 24 (27.9%) patients were in Tis category while 30 (34.9%) patients were in T4 category. Twenty-eight (32.6%) patients received complete course of adjuvant topical mitomycin C (0.04%) while nine (10.5%) patients completed adjuvant systemic chemotherapy and external beam radiation. Overall, 61 (70.9%) patients had no tumor recurrence, seven (8.1%) patients had recurrent tumor, while the status of 18 (20.9%) patients was not known. OSSN occurs more commonly in younger age group in our studied population and is strongly associated with HIV seropositivity. Intraoperative cryotherapy in patients with carcinoma in situ and intraoperative cryotherapy with adjuvant topical mitomycin C in those with invasive SCC that is limited to the ocular surface are associated with low tumor recurrence.

Left secondary carinal resection and reconstruction for low-grade bronchial malignancies.

ObjectivesA rare and complex procedure, total lung sparing left secondary carinal resection and reconstruction is only performed in a few specialized centers in a restricted group of patients. We reviewed our experience to evaluate its safety.MethodsPatients who underwent left secondary carinal resection and reconstruction with complete lung parenchymal preservation for low-grade bronchial malignancies at the Shanghai Chest Hospital and the Padua University Hospital were retrospectively reviewed. Clinicopathologic factors and perioperative outcomes were analyzed.ResultsThirty patients underwent the procedure between July 2012 and July 2019 (mean age, 42.9 years). No operative mortality occurred and postoperative complications developed in 4 patients (13.3%), including pneumonia (n = 3 [10.0%]), subcutaneous emphysema (n = 2 [6.7%]), and prolonged air leak (n = 2 [6.7%]). Pathologies included adenoid cystic carcinoma (n = 11), mucoepidermoid carcinoma (n = 6), carcinoid tumors (n = 9 [8 typical and 1 atypical subtypes]), inflammatory myofibroblastic tumor (n = 3), and myoepithelioma (n = 1). The margins were positive in 8 patients (26.7%), whereas 2 patients (6.7%) had positive lymph nodes. Adjuvant therapies were performed postoperatively, including chemoradiotherapy for positive lymph nodes and radiotherapy for positive margins.ConclusionsTotal lung sparing left secondary carinal resection and reconstruction can be performed safely in well-selected and oncologically appropriate patients with low-grade bronchial malignancies.

Minimally invasive pancreatic resection in the light of evidence state of the art.

The trend of minimally invasive surgery expands even into the most technically demanding areas, including HPB surgery. Faster recovery and elimination of surgical site infections achieved with a minimally invasive approach provides, in addition to a better quality of life, the possibility of starting adjuvant treatment earlier. However, evidence of non-inferiority of short-term and oncological results compared to open surgery is required. In minimally invasive distal pancreatectomy, there is sufficient evidence to suggest that it as the method of choice for benign tumors and low-grade malignancies. For pancreatic cancer, the long-term results so far appear to be equivalent, although this still needs to be confirmed by ongoing randomized controlled trials (RCT). Enucleation of accessible lesions is also a suitable procedure for the minimally invasive approach. In contrast, in pancreaticoduodenectomy, available evidence does not demonstrate a clear benefit of the minimally invasive approach. Safety concerns still remain, and not even formal training has been successful in eliminating the consequences of the long learning curve for perioperative outcomes. Robotic approach appears to be more promising than laparoscopy for pancreaticoduodenectomy. Key words: pancreaticoduodenectomy distal pancreatectomy minimally invasive - laparoscopic robotic.

Primary ciliated muconodular papillary tumor: A rare pulmonary disease and literature review of 65 cases.

A ciliated muconodular papillary tumor (CMPT) or bronchiolar adenoma (BA) is a rather rare and unique type of lung tumor characterized by tripartite cellular components with a papillary‐predominant structure including ciliated columnar cells, mucinous cells, and basal cells. Here, we present the case of a 64‐year‐old woman who was diagnosed with CMPT in our center. In addition to reporting the clinicopathological characteristics of this case, we also conducted whole exome sequencing (WES) to explore the underlying mechanism. According to current evidence, CMPTs tends to be benign or of low grade malignancy. However, this requires further validation.

Sertoliform Endometrioid Carcinomas of the Right Ovary

Abstract Background: Endometrioid carcinomas of the ovary are a sub-type of epithelial ovarian tumors. The vast majority are malignant and invasive. On imaging, they are usually characterized as complex nonspecific solid-cystic masses and found associated with endometriosis. However, endometrioid carcinoma of ovary resembling sex cord-stromal tumor is a rare variant of endometrioid adenocarcinoma that focally looks like a sex cord-stromal tumor with sertoli, leydig, or granulosa cells. Sertoliform endometrioid carcinoma of the ovary (SEC) is one variant that bears histologic similarity to Sertoli and Sertoli-Leydig cell tumors (SLTs). Clinical Case: A 47 year old, premenopausal female, presented with rapid growing hirsutism, frontal hair loss, abdominal distension and constipation for less than one year. On clinical examination modified Ferriman-Gallwey (mFG) score was 17/36. Abdominal examination showed a palpable mass in lower abdomen, 25cm in size, rounded, and hard in nature. CT abdomen and pelvis revealed large pelvic abdominal mass (21x20.5x17 cm) with cystic and basal soft tissue components related to right ovary. Preoperatively laboratory investigations showed FSH 9.96 mIU/mL, LH 15.4, Estradiol (E2) 94.7 pg/ml, raised total testosterone 4.38 nmol/l, normal SHBG 34 nmol/l and normal DHEA-S 161 microg/dl. Total abdominal hysterectomy and bilateral salpingo-oophorectomy was done, in which the right ovary was seen to be replaced by a solid cystic tumor with ruptured capsule. Grossly, the right ovary was enlarged measuring 9.5 cm × 8 cm × 4.8 cm. Microscopy showed round to solid tubules lined by pseudostratified columnar epithelium with elongated nuclei resembling sertoli tumor-like pattern along with conventional endometrioid tumor. A histopathological diagnosis of SEC of right ovary was made. Immunohistochemistry showed tumor cells strongly immunoreactive for epithelial membrane antigen (EMA), cytokeratin (CK) but negative for inhibin, thus confirming the diagnosis of SEC of right ovary. Conclusion: SEC is extremely rare variant of endometrioid carcinomas and tend to present at an earlier stage as compared with most endometrioid carcinomas of the ovary. Recognition of SEC in virilizing patients is important as it is a well-differentiated, low-grade malignancy that displays a good prognosis when confined to the ovary.

ASSOCIATION BETWEEN APPARENT DIFFUSION COEFFICIENT AND KI67 IN BRAIN TUMORS: A SYSTEMATIC REVIEW

Certain histological variants of tumors have a correlation between the values of the apparent diffusion coefficients (AdC), cell density and the proliferative activity index MIB-I (Ki67). The results of studies on the relationship between the values of the AdC and the Ki67 index in brain tumors are ambiguous and largely contradictory. The purpose of this study was to perform a systematic review based on the results of clinical studies that examined the relationship between AdC values and the Ki67 proliferative activity index in brain tumors. Material and Methods . Clinical studies were searched in the databases pubmed, EMBASE, Cohrane Library and eLibrary published from January 2000 to January 2020, which studied the relationship between AdC values and the Ki67 proliferative activity index in brain tumors. Results . A systematic review included 17 retrospective cohort nonrandomized clinical studies. The average value of the coefficient of reliable correlation between AdC and the mitotic index Ki67 in the group of meningiomas was -0.493. The indicated dependence was more often found in groups of typical (MI) and atypical (MII) brain meningiomas. The average coefficient of statistically significant correlation between the studied parameters in the group of brain gliomas was -0.443. The relationship between the AdC values and the Ki67 proliferative activity index was observed both in the glioma group of low (GI–II) and high (GIII–IV) grade of malignancy. In groups of patients with pituitary adenomas, primary lymphomas and brain metastases, the relationship between the studied parameters was not reliably confirmed. Conclusion. The use of diffusion-weighted magnetic resonance imaging techniques with subsequent calculation of AdC values can be recommended for use in the clinical practice of oncologists in order to assess the proliferative potential of brain meningiomas and gliomas.

Neuroendocrine Neoplasms of the Lung

Abstract In this review, we discuss the clinical and pathologic aspects of epithelial neuroendocrine neoplasms of the lung and compare the current classification with that of gastrointestinal (GI) neuroendocrine neoplasms. Endocrine neoplasms can be broken down into 2 major categories, which, as currently believed, are not part of a continuum, but rather distinct pathogenetic entities. Well-differentiated neuroendocrine tumors (NETs) are low-grade malignancies. In the lung, the term “carcinoid” is still applied for these, which are classified as typical or atypical. In the pancreas and GI tract, well-differentiated NETs are graded based on Ki-67 proliferative index into 3 numeric categories. Poorly differentiated neuroendocrine carcinomas (NECs) are classified in both organ systems into small cell carcinoma and large cell NEC. In this review, “NET” is used interchangeably with “well-differentiated NET.” Although often used in the GI tract, “poorly differentiated NEC” is not a term used in the lung, where the distinction between small cell carcinoma and LCNEC is more clear-cut than in the GI tract.

¿Un tumor del tracto urinario superior resulta siempre en nefroureterectomía? Manejo conservador endoscópico de un tumor del tracto urinario superior: reporte de un caso

Background: Historically, nephroureterectomy has been considered the treatment of choice for an upper urinary tract tumor. However, current literature supports a conservative endoscopic management in case of low-grade tumors and in patients in whom a radical surgery could represent an important morbidity. Therefore, an accurate diagnosis is essential to identify patients who may benefit from conservative treatment. Case report: A 75-year-old patient diagnosed with an upper urinary tract tumor of approximately 2 cm located in the upper right renal calyx. We performed an endoscopic ablation of the tumor with Holmium laser using a flexible 8.5 Fr ureteroscope. The surgery was uneventful and the patient was discharged the next day. The tumor biopsy reported a papillary urothelial neoplasm of low malignant potential. At 3 months, an endoscopic second-look was performed where no persistence or recurrence of the disease was evidenced. Conclusion: Conservative endoscopic management of upper urinary tract tumors is a suitable alternative for low-grade malignancy lesions, maintaining good oncological results and low complication rates. This procedure takes even more prominence in comorbid or single-kidney patients, in whom radical surgery represents a high surgical and medical risk.

Outcomes and issues of 12 chordomas treated in a single center

BackgroundChordomas stem from notochordal vestiges and rank as low-grade bone malignancies although fraught with high risk of recurrence. This study assesses the clinical outcomes of twelve chordoma cases treated in our clinic, in an effort to shed light on the often under-represented pool of results deriving from non-referral centers.MethodsWe reviewed the clinicopathological traits of all chordoma patients registered in our center since 1991. Major endpoints were overall survival (OS) and progression-free survival (PFS) estimated using the Kaplan–Meier and Nelson–Aalen methods.ResultsTwelve patients, aged on average 47.9 years, were treated for primary or recurrent disease. Seven had chordomas originating in the cranium, 5 in the spine, including a bifocal tumor, and the mean time lapse between the beginning of symptoms and diagnosis was 15.4 months, marked by dull ache. Subtotal resection was achieved in 5 cases, incomplete in 5, while in 2, only biopsy was accomplished. Conformal radiotherapy was administered to 5 and stereotactic radiosurgery to 2 in the setting of recurrence. Protons were used once and targeted agents induced no clinical response in 3 patients. Median OS and PFS were 36 and 12 months, respectively, with the best outlook linked to maximal resection, spinal location, and good preoperative functional status. In all, 6 patients died of chordoma, 4 are alive, and 1 was lost. Relapse was the rule for most cases, except 2, and pulmonary metastases were ascertained in 1.ConclusionsOur cases were typical of chordomas, implying that inadequate surgical margins and successive recurrence are negative determinants of prognosis and that interinstitutional cooperation counterbalances shortages in non-referral institutes.

Association between surgical excision margins and outcomes in patients with dermatofibrosarcoma protuberans: A meta‐analysis

Dermatofibrosarcoma protuberans (DFSP) is a tumor with low-grade malignancy and high recurrence rates. Wide local excision (WLE) is essential for DFSP, but its surgical excision margin is controversial. This study aimed to examine whether resection margin is associated with the prognosis of patients with DFSP by systematically reviewing related literature. Studies that evaluated the relationship between excision margins and outcomes after WLE were retrieved from the Cochrane Library, PubMed, Embase, and Web of Science databases. Relative risk (RR) estimates and 95% confidence intervals (CIs) were measured via a random-effect model to evaluate the subsequent outcomes: recurrence rate, mortality, and positive surgical margin rate. Sensitivity and subgroup analyses were simultaneously carried out. The meta-analysis of eight observational literatures demonstrated a significant positive correlation of ≥3cm margin with the recurrence rate (RR=0.17, 95% CI 0.09-0.31) and the positive surgical margin rate (RR=0.09, 95% CI 0.02-0.46). The same result was observed in the recurrence rate in all subgroups. The stability of the above outcomes was authenticated via sensitivity analyses. Our meta-analysis illustrated that excision with <3cm surgical margin exhibited an increased risk of poor DFSP prognosis (high recurrence rate and increasing positive margin rate).

Critical review of multidisciplinary approaches for managing sinonasal tumors with orbital involvement.

SUMMARYOrbital invasion is frequently observed in tumors involving the maxillary, ethmoid and frontal sinuses given the proximity of the orbit to the sinonasal tract and ventral skull base. The main objective of the present review is to determine the existing evidences on the frequency, treatment, and outcomes of orbital invasion in benign and malignant sinonasal tumors. A systematic review of the literature published from 1995 to 2020 was performed and data sources included PubMed, Cochrane library, NCBI Bookshelf, National Guideline Clearinghouse. Orbital invasion was reported in 2-4% of inverted papillomas, 12-15% of fibro-osseous lesions, 27-32% of juvenile angiofibromas, 35-45% of low-grade malignancies, and 50-80% of high-grade cancers. Surgical resection with negative margins represents the cornerstone of management for benign and low-grade malignant tumors. Histology-specific induction chemotherapy can be used for high-grade sinonasal cancers in order to downstage the tumor and increase the possibility of orbital preservation. When a significant response to induction chemotherapy is observed, exclusive chemoradiation should be offered to improve overall survival rates. Appropriate reconstruction of any surgical defects is essential in order to minimize complications and optimize functional and aesthetic outcomes. Orbital apex invasion represents a negative prognostic factor. In conclusion, a multidisciplinary teamwork is mandatory to maximize local control, minimize morbidity and improve orbital preservation rates.

Solid-Pseudopapillary Neoplasm of the Pancreas: A 63-Case Analysis of Clinicopathologic and Immunohistochemical Features and Risk Factors of Malignancy

PurposeSolid-pseudopapillary neoplasm (SPN) of the pancreas, a rare tumor, has low malignant potential. However, some patients develop metastasis and recurrence after resection, with aggressive biological behaviors. This study aimed to explore the features and risk factors associated with the aggressive biological behaviors of SPNs.Patients and MethodsWe retrospectively analyzed the clinicopathological and long-term follow-up data of 63 patients diagnosed with SPN at the First Affiliated Hospital of Bengbu Medical College between January 2007 and February 2019.ResultsSixty-three patients presented atypical clinical symptoms. The median tumor size was 7.0 cm (range, 2.4–17 cm), and imaging features were solid and cystic or solid tumors with uneven density. Frequent and diffuse nuclear LEF1 protein expression (94.2%) was observed with LEF1 having a higher sensitivity and specificity. Overall survival significantly correlated with tumor size, Ki-67 index, and lymph node metastasis (P < 0.05).ConclusionSPN is a rare low-grade malignancy with a specific pseudopapillary structure. LEF1 is an effective biomarker of SPNs. Although SPNs generally display indolent biological behavior, a large tumor size, high proliferation index, and lymph node metastasis may be risk factors for the aggressive behavior and poor prognosis of SPN.