Clinical Outcomes of Low Histologic Grade Follicular Lymphoma with High Proliferation Index

Background: Follicular lymphoma (FL) is the second most common subtype of non-Hodgkin lymphoma (NHL) accounting for ~35% of NHL and often have a clinically indolent course. PET/CT max SUV ≥10 and high proliferative index are associated with FL at high risk for transformation to aggressive lymphoma (Schöder, 2005; Rossi, 2020). A subset of patients (pts) with low histologic grade and high proliferation index (LG-HPI) have a more aggressive clinical course with inferior overall survival (OS) compared to low grade, low proliferation index (LG-LPI) FL patients (Wang, 2005). The aim of our study was to identify outcomes for patients with LG-HPI FL at our institution. Methods: We conducted a single center, retrospective study of FL diagnosed from 1/1/2015-1/1/2021. Demographic information, diagnoses, laboratory results, medications, pathology, and radiology reports were collected from pts' electronic medical records. Pathology specimens were de-identified and retrospectively reviewed by two pathologists. Review included comprehensive evaluation of histologic grade, proliferation index by Ki-67 percentage (Ki-67%), immunohistochemical staining, and c-MYC immunohistochemical staining. Biopsies were classified as LG-LPI if Grade 1-2 and Ki-67 was <30%, LG-HPI if Grade 1-2 and Ki-67 was ≥30%, and high grade (HG) if Grade 3A or 3B. The primary endpoint was progression free survival (PFS) defined as time from treatment until time of progression and last known follow up as determined by Kaplan-Meier method. OS was calculated from time of diagnosis to last follow up or death by Kaplan-Meier method. Comparisons were made using Log-rank model and Cox Proportional Hazards Model. Time to first treatment (TTFT) was calculated as time from diagnosis to first treatment. Receiver operating curve (ROC) was used to determine correlation between PET SUV values (defined as ≥10, or <10) and Ki-67%. Results: 152 pts were diagnosed with FL and included for analysis. Patient characteristics are summarized in Table 1. Median age at diagnosis for all pts was 65.9 years. Sixty-three pts had LG-LPI, 61 LG-HPI, and 28 HG pts. Ten pts transformed to DLBCL (2 LG-LPI, 5 LG-HPI, 3 HG). Treatment regimens included initial observation (n = 44), anti-CD20 therapy alone (n = 24), chemo-immunotherapy (n = 53), and other (n = 31). Median TTFT was 1.27 mo (range 0-115.2 mo). There was moderate correlation between SUV of biopsied lesion ≥10 and Ki-67 percentage (ROC Area 0.6175). Median PFS was longer for LG-LPI compared to LG-HPI (78.6 vs 57.8 mo, p = 0.04, HR 2.37) but not between LG-HPI and HG (57.8 vs 61.3 mo respectively, p = 0.32) (Figure 1A). Median OS was not reached in any cohort with median follow up of 29.5 mo. There was no difference in OS between LG-LPI vs LG-HPI (p = 0.53) (Figure 1B). Histologic grade, proliferation index, Ann Arbor Staging, FLIPI score, PET/CT SUV intensity (max or of biopsied lesion), presence of c-Myc staining, or initial treatment regimen were not associated with median PFS or OS in either subgroup on univariate analysis. Conclusions: In our cohort, PFS was shorter for LG-HPI compared to LG-LPI but with a similar trajectory to that of HG FL, consistent with prior reports. No differences were seen in OS between LG-HPI and LG-LPI, and no covariates of interest including histologic grade, proliferation index, Ann Arbor Staging, FLIPI score, PET/CT SUV intensity, presence of c-Myc staining, or initial treatment regimen were associated with differences in PFS or OS. Our study is limited by a short follow up time compared to prior published cohorts (29.5 vs 98.4 mo). PET/CT SUV values of ≥10 have moderate predictive value for higher proliferative disease and can aid in identifying patients with higher proliferative disease. Longer follow up is needed to determine if LG-HPI impacts OS. References: 1. SchöderH, et al. Intensity of 18fluorodeoxyglucose uptake in positron emission tomography distinguishes between indolent and aggressive non-Hodgkin's lymphoma. J Clin Oncol 2005;23:4643-51. 2. Rossi C, et al. Baseline SUVmaxis related to tumor cell proliferation and patient outcome in follicular lymphoma. Haematologica 2020;Online ahead of print. 3. Wang SA, et al. Low histologic grade follicular lymphoma with high proliferation index: morphologic and clinical features. Am J Surg Pathol2005;29:1490-6. Figure 1 Figure 1. Disclosures Allen: Sanofi Genzyme: Membership on an entity's Board of Directors or advisory committees; C4 Therapeutics: Other: Equity Ownership; Bristol Myers Squibb: Other: Equity Ownership; Alexon: Research Funding. Rhodes: Conquer Cancer Foundation Young Investigator Award: Other: Grant/Research Support; AbbVie, Genentech, Pharmacyclics, TG Therapeutics: Other: Consultant.

Acroangiodermatitis or pseudo-Kaposi’s sarcoma: a challenging diagnosis

Acroangiodermatitis (AAD), also referred to as pseudo-Kaposi’s sarcoma, is a vascular-proliferative disease characterized by reactive proliferation of small blood vessels in response to congenital or acquired vascular lesions. There are mainly two clinical variants of acroangiodermatitis; STEWART-BLUEFARB syndrome and the Malian type. There is clinical and histological similarity with Kaposi’s sarcoma hence the interest of immunohistochemical analysis. We report the case of a 40-year-old man with cutaneous lesions localized on the lower limbs. Clinical, dermoscopic, histological and immunohistochemical investigation led to a diagnosis of Kaposi-like acroangiodermatitis.

Efficacy and Safety of Apremilast versus Methotrexate in the Treatment of Chronic Plaque Psoriasis

Introduction: Psoriasis is a common, chronic, inflammatory and proliferative disease of the skin, also affecting nail and joints. Although there are a range of treatment options available, none have proved to wane the symptoms fully and also they reappear in course of time. Aim: To explore the safety and efficacy of Apremilast and Methotrexate on chronic plaque psoriasis patients. Methods: A randomized open clinical trial was done among fifty clinically diagnosed chronic plaque psoriasis patients in the Department of Dermatology and Venereology at Combined Military Hospital (CMH), Dhaka from 1st July 2017 to 30th June 2018. Patients were divided randomly into two equal treatment groups, 25 for Methotrexate and 25 for Apremilast. Involvement of body surface by plaque psoriasis, erythema, scaling and induration were recorded in a 3 points scale before treatment and 8 weeks after starting the treatment and finally at 12th week. Results: Reduction of psoriasis at 1st follow up in Methotrexate and Apremilast groups were 29.9±9.0 and 31.9±11.6 respectively and at 2nd follow up were 85.9±7.3 and 28.48±39.3 respectively. Significantly higher improvements were observed in Methotrexate group than Apremilast group both at 1st and 2nd follow up (p=0.001). Conclusion: Methotrexate is a better therapeutic option than Apremilast in the treatment of chronic plaque psoriasis. JAFMC Bangladesh. Vol 15, No 1 (June) 2020: 39-41

Correlation of Retinopathy of Prematurity with Oxygen Saturation

Retinopathy of prematurity (ROP) is an abnormal vascular proliferative disease of retina that affects preterm infants. It is a leading cause of childhood blindness worldwide despite improvement in neonatal care and management. Earlier ROP was found to be associated with oxygen therapy only. Now it was concluded that aetiology of ROP was multifactorial but three factors have shown significant association with ROP: low gestational age (GA), low birth weight (BW), prolonged exposure to supplementary oxygen following delivery. Several investigators reported that lower oxygen saturation targets at young post-gestational ages with increased oxygen saturation targets at older post gestational ages reduced the incidence of ROP. However previous clinical studies are not conclusive.

Generalised eruptive histiocytosis preceded by systemic symptoms

Generalised eruptive histiocytosis is a rare proliferative disease that typically presents with indolent cutaneous eruptions. We describe the case of a 73-year-old man presenting with diffuse, asymptomatic crops of pink to dusky red papules preceded by general malaise, myalgias, fluctuating fever, chills, and weight loss. Histological evaluation revealed a non-Langerhans cell histiocytic dermal infiltrate with spindle cell features and chronic inflammation, reactive for CD68 and negative for both S100 and CD1a. Malignancy screening was negative. This report aims to highlight a unique presentation of generalised eruptive histiocytosis, emphasise histological findings, and discuss considerations for malignancy screening.

Cutaneous Rosai–Dorfman disease: a challenging diagnosis

Rosai–Dorfman disease is a rare benign histiocytic proliferative disease of unknown cause that, in exceptional cases, presents with lesions confined to the skin. Clinically variable types of lesions such as papules, nodules and plaques have been reported. We present a case of a 27-year-old woman with a 1-year history of erythematous papular and nodular lesions on the malar and right axillary regions, previously misdiagnosed as acne. She reported no fever, malaise or weight loss, while physical examination and laboratory workup were normal. Bacteriological and mycobacteriological cultures were negative. Histopathological findings showed dense infiltration of inflammatory cells involving the entire dermis, consisting of large macrophages with emperipolesis, S100 and CD68 positive, neutrophils, eosinophils, lymphocytes and plasma cells. The patient was treated with oral prednisolone without improvement. Dapsone was subsequently initiated with favourable clinical response. The present article aimed to emphasise the clinical and histological differential diagnosis and share the treatment experience.

Diabetic Vitrectomy

Diabetic retinopathy (DR) in its advanced stage is a leading cause of blindness and visual impairment. Despite efforts at early detection of DR, disease monitoring, and medical therapy, significant proportions of people living with diabetes still progress to develop the advanced proliferative disease, which is characterized by neovascularization, actively proliferating fibrovascular membranes, and retinal traction. The surgical removal of this proliferating tissue and the treatment of the retinal ischemic drive can be very rewarding, providing significant stability of the retina and in several cases improved retinal anatomy and vision. Diabetic vitrectomy comprises a broad range of surgical techniques and maneuvers, which offer the surgeon and patient opportunity to reverse deranged vitreoretinal anatomy and improve or stabilizes vision. Advances in vitreoretinal technology have contributed greatly to more recent improved outcomes; it is expected that future advances will offer even more benefit.

Recent Advances in Desmoid Tumor Therapy

The desmoid tumor is a locally aggressive proliferative disease within the family of soft-tissue sarcomas. Despite its relatively good prognosis, the clinical management of desmoid tumors requires constant multidisciplinary evaluation due to its highly variable clinical behavior. Recently, active surveillance has being regarded as the appropriate strategy at diagnosis, as indolent persistence or spontaneous regressions are not uncommon. Here, we review the most recent advances in desmoid tumor therapy, including low-dose chemotherapy and treatment with tyrosine kinase inhibitors. We also explore the recent improvements in our knowledge of the molecular biology of this disease, which are leading to clinical trials with targeted agents.