Efficacy and safety of topical 0.5% 5-Fluorouracil as primary treatment of ocular surface squamous neoplasia.

OBJECTIVE: To assess the efficacy and safety of topical 0.5% 5-Fluorouracil (5-FU) as a primary therapy of ocular surface squamous neoplasia (OSSN). DESIGN: Retrospective study. PARTICIPANTS: Patients with clinically suspected OSSN referred to a Brazilian tertiary health center between October 2015 and December 2022. METHODS: After diagnostic confirmation of OSSN with exfoliative cytology, 0.5% 5-FU was administered topically 4 times daily for 2 weeks followed by a pause of 2 weeks. RESULTS: A total of 54 patients were included in this study, 32 males (59.3%), mean age of 62.9 years old. Complete resolution of OSSN was achieved in 70.4%. The median number of cycles was 2 (range 1-5). Side effects were reported in 35.2%, which included eyelid erythema, conjunctival hyperemia, and punctal stenosis. None of the patients stopped treatment due to adverse effects. Patients who had partial response to 0.5% 5-FU had complementary treatment with surgery, Mitomycin-C and/or Interferon ⍺2b. Overall recurrence was 14.8%. Median follow-up was 14 months (range 2-92 months). In a multivariate Cox regression analysis, the risk of relapse was 84% lower in patients who had complete response to 0.5% 5-FU (p = 0.018). CONCLUSION: Topical 0.5% 5-FU may be considered a safe and effective primary therapy for OSSN, with a low rate of side effects.

MASSIVE RETINAL NEOVASCULARIZATION IN VON HIPPEL-LINDAU DISEASE: ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR, VITRECTOMY, IMMUNOHISTOCHEMISTRY, AND OPTICAL COHERENCE TOMOGRAPHY FEATURES.

PURPOSE: To report a rare presentation of ocular von Hippel-Lindau disease associated with a massive epiretinal vascular proliferation over the macula removed by vitrectomy and submitted to histological analysis. METHODS: Interventional case report. RESULTS: A 13-year-old woman with von Hippel-Lindau disease reported progressive visual loss in the right eye over the preceding 6 months. Best-corrected visual acuity was 20/100 in the right eye. Fundoscopy showed retinal neovascularization (RNV) with macular traction and a small superotemporal hemangioblastoma. Spectral-domain optical coherence tomography confirmed increased macular thickness and macular traction secondary to RNV. Bevacizumab was injected intravitreally, resulting in partial regression of RNV. Five days after the injection, the patient underwent complete removal of fibrovascular proliferation via pars plana vitrectomy, followed by peripheral tumor photocoagulation. The specimen was subjected to histopathological and immunohistochemical analyses. At 2 years of follow-up, vision had improved to 20/30, and anatomical improvement was confirmed on both fundoscopy and spectral-domain optical coherence tomography. CONCLUSION: Ocular von Hippel-Lindau disease may be associated with RNV and macular traction. In such cases, RNV is likely responsive to anti-vascular endothelial growth factor and may be removed surgically along a cleavage plane between the tissue proliferation and the inner retina. In the reported case, the procedure was found to be safe and associated with macular anatomical improvement and vision recovery.

Blood Flow in Monocular Retinoblastoma Assessed by Color Doppler and Correlations With High-Risk Pathologic Features.

Purpose: To use color Doppler to analyze blood flow in the retrobulbar central retinal artery (CRA) and central retinal vein (CRV) in monocular retinoblastoma. Methods: This prospective study included patients with group D and E retinoblastomas managed with only enucleation. Peak blood velocities were assessed in the CRA and CRV of tumor-containing eyes (CRAv and CRVv, respectively). The resistivity index in the CRA (RIa) and pulse index in the CRV (PIv) were calculated and related to optic nerve invasion (ONi), choroid invasion (mCHi), and tumor volume. RIa and PIv were also calculated for healthy eyes. Results: In total, 25 patients with a mean age of 30.8-months old were included. The means (SD) for CRAv, CRVv, RIa, and PIv were 26.94 (12.32) cm/s, 16.2 (9.56) cm/s, 0.88 (0.12) and 0.79 (0.29), respectively. Tumor volume was significantly correlated with CRAv (P = 0.025) and RIa (P = 0.032). ONi was present in 19 eyes and correlated with a smaller PIv (P < 0.001). A PIv less than 0.935 had a sensitivity of 89.5% and specificity of 83.3% for predicting ONi. mCHi was not correlated with flow values. Healthy eyes had a significantly lower RIa (P < 0.001) and lower PIv than eyes with (P = 0.009) and without (P < 0.001) ONi. Conclusions: In advanced-stage monocular retinoblastoma, tumor volume was directly correlated with CRAv and RIa, and lower PIv was correlated with optic nerve invasion when a predictive cut-off value of less than 0.935 was applied. Comparisons with healthy eyes showed that tumor-containing eyes were associated with higher RIa and PIv values.

Epithelial-Myoepithelial Carcinoma of the Lacrimal Gland 14 Years After En Bloc Resection of a Pleomorphic Lacrimal Gland Adenoma.

Fourteen years after en bloc resection of an orbital pleomorphic adenoma, a 61-year-old female patient developed progressive left proptosis on the same side. A CT scan revealed a round, well-circumscribed, heterogeneously enhancing mass in the lacrimal fossa of the left orbit without calcification or bone erosion. An MRI scan showed a lesion that was hypointense on T1-weighted images and heterogeneously isointense on T2-weighted images. The tumor was completely resected through combined anterior and lateral orbitotomy. On histopathology, the specimen was identified as epithelial-myoepithelial carcinoma. After surgery, the patient received adjuvant therapy with irradiation of the orbit. At a 36-month follow-up evaluation, the patient remained tumor-free. Epithelial-myoepithelial carcinoma, a very uncommon tumor of the orbit, apparently behaves like a low-grade malignancy and is associated with good survival rates. However, a good prognosis for survival is tentative at best, in part because of the rarity of the lesion.

Imiquimod cream efficacy in the treatment of periocular nodular basal cell carcinoma: a non-randomized trial.

BACKGROUND: The recurrence rate of periocular nodular basal cell carcinoma (PNBCC) following treatment with imiquimod (IMQ) has not yet been established. Previous studies did not include histological follow-up. The aim of this analysis was to evaluate the efficacy of topical immunotherapy with 5% IMQ cream for the treatment of PNBCC. STUDY DESIGN: A prospective, non-randomized, and uncontrolled longitudinal case series study. No participants were blinded. Punch biopsy confirmed PNBCC patients were included at the Ophthalmology Clinic of São Paulo University Medicine School Hospital (from 2008 to 2012). Patients were treated with 5% IMQ cream once a day, 5 days per week, for 8-16 weeks. Standard lesion photographic documentation was done during the study. Three months after treatment ended, an image-guided biopsy was performed. Patients were followed at 6-month intervals and annually for control biopsies. Main outcome measures were clinical and histological clearance rates. Data were analysed by frequency distribution for qualitative group characteristics and central tendency measures for quantitative data. RESULTS: Twenty-four patients met the inclusion criteria, 19 of whom remained until the end of treatment. The histological clearance rate was 89.5% and 84.2%, respectively, at 3 and 39.5 months. The 3-year histological clearance rate was 81.8% (9/11) for lesions >10 mm, and 100% (8/8) for lesions <10 mm. Three patients did not tolerate the side effects of the medication and left the study. Two patients were excluded for treatment interruption related to comorbidities. CONCLUSIONS: Our results indicated that 5% IMQ cream was a useful alternative treatment for NBBCC, especially for lesions <10 mm. IMQ also showed a significant neoadjuvant effect on lesions >10 mm. TRIAL REGISTRATION: ClinicalTrial.gov Registration Dec 3, 2008: # NCT 00803907.

Blood flow velocity in monocular retinoblastoma assessed by color Doppler.

OBJECTIVE: To analyze the flow of retrobulbar vessels in retinoblastoma by color Doppler imaging. METHODS: A prospective study of monocular retinoblastoma treated by enucleation between 2010 and 2014. The examination comprised fundoscopy, magnetic resonance imaging, ultrasonography and color Doppler imaging. The peak blood velocities in the central retinal artery and central retinal vein of tumor-containing eyes (tuCRAv and tuCRVv, respectively) were assessed. The velocities were compared with those for normal eyes (nlCRAv and nlCRVv) and correlated with clinical and pathological findings. Tumor dimensions in the pathological sections were compared with those in magnetic resonance imaging and ultrasonography and were correlated with tuCRAv and tuCRVv. In tumor-containing eyes, the resistivity index in the central retinal artery and the pulse index in the central retinal vein were studied in relation to all variables. RESULTS: Eighteen patients were included. Comparisons between tuCRAv and nlCRAv and between tuCRVv and nlCRVv revealed higher velocities in tumor-containing eyes (p < 0.001 for both), with a greater effect in the central retinal artery than in the central retinal vein (p = 0.024). Magnetic resonance imaging and ultrasonography measurements were as reliable as pathology assessments (p = 0.675 and p = 0.375, respectively). A positive relationship was found between tuCRAv and the tumor volume (p = 0.027). The pulse index in the central retinal vein was lower in male patients (p = 0.017) and in eyes with optic nerve invasion (p = 0.0088). CONCLUSIONS: TuCRAv and tuCRVv are higher in tumor-containing eyes than in normal eyes. Magnetic resonance imaging and ultrasonography measurements are reliable. The tumor volume is correlated with a higher tuCRAv and a reduced pulse in the central retinal vein is correlated with male sex and optic nerve invasion.

Hemophagocytic lymphohistiocytosis associated with hepatosplenic T-cell lymphoma: case report.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare non-Hodgkin lymphoma, marked by liver, spleen, and bone marrow sinusoidal infiltration, with an aggressive clinical course, which represents a difficult diagnostic task for clinicians and pathologists. Another equally severe and challenging condition is the hemophagocytic lymphohistiocytosis (also called hemophagocytic syndrome [HS]), which is often associated with hematologic malignancies and infectious diseases. The authors report the case of a 56-year-old woman diagnosed with HSTCL based on bone marrow aspirate flow cytometry and skin biopsy. The patient underwent a cycle of chemotherapy but the outcome was unfavorable with multiple organ failure. The laboratory analysis was consistent with HS. The autopsy confirmed both the remaining lymphoma in the pulmonary vessels and the hemophagocytic cells in the spleen and bone marrow.

Prune-belly syndrome: an autopsy case report.

Prune-belly syndrome (PBS) is a rare congenital anomaly characterized by a spectrum of mild-to-severe presentations of urinary tract malformations, deficient abdominal wall musculature, and cryptorchidism in male newborns or genital abnormalities in the female newborns. Currently, antenatal diagnosis is feasible with ultrasound examination, and treatment is based on case report experience. More recently, intrauterine management has been undertaken with encouraging results. The authors report a case of PBS diagnosed at the seventeenth gestation week, when ultrasonographic examination revealed the presence of ascites, distended bladder, thickened bladder wall and posterior urethral valve. The fetus was submitted to an intrauterine intervention at the nineteenth gestational week. Delivery occurred at 34 weeks of gestation and the newborn examination was consistent with PBS. On the second day of life, the newborn was submitted to abdominoplasty, colostomy, and orchiopexy. However, the outcome was unfavorable with respiratory failure and death on the fifteenth day of life. The autopsy confirmed the diagnosis of PBS, but the immediate cause of death was attributed to aspiration pneumonia.

Wharton's jelly absence: a possible cause of stillbirth.

The umbilical cord is a structure that provides vascular flow between the fetus and the placenta. It contains two arteries and one vein, which are surrounded and supported by gelatinous tissue known as Wharton's jelly. There are many umbilical cord abnormalities that are related to the prognosis of fetus survival and birth weight. The authors report a case of umbilical cord constriction due to the localized absence of Wharton's jelly, which was undiagnosed antenatally and had a fatal outcome. A review of the association between the absence of Wharton's jelly and an unfavorable pregnancy outcome was undertaken.

Mucinous adenocarcinona of the appendix.

Diagnosis of malignancy in the vermiform appendix is quite rare. The most common histological malignant neoplasia found in this tiny portion of the gastrointestinal tract is represented by the mucinous adenocarcinoma. This entity predominates in males around 50 years of age, and clinical presentation usually mimics or occurs along with an acute appendicitis. Early diagnosis is outside the rule since most cases at this stage are symptomless. The authors present the case of a 59-year-old female patient who looked for medical attention complaining of abdominal pain. Physical examination and laboratory workup were poor in diagnostic findings. The computed tomography images were compatible with the diagnosis of appendicitis and/or appendiceal neoplasia. The patient underwent a laparotomy and right hemicolectomy. The histological examination disclosed a moderately differentiated mucinous adenocarcinoma of the appendix stage T4a, N0, M0. The patient outcome was uneventful and was referred to an oncological center.

Partial vaginal expulsion of a leiomyosarcoma.

Uterine sarcomas are an uncommon and heterogeneous group of tumors that account for 3-7% of the malignant neoplasms of the uterus and approximately 1% of all malignant tumors of the female genital system. The main clinical manifestations are abnormal uterine bleeding in pre- or postmenopausal women. Pelvic pain, abdominal distension, urinary urgency, and profuse and fetid leukorrhea are other frequent complaints. The authors present a case of a 48-year-old patient that was in amenorrhea for 2 years, who sought treatment for vaginal bleeding. On physical examination, the abdomen was distended, painful in the hypogastrium and upon examination of the external genitalia, it was observed the exteriorization of an amorphous "mass". The patient was submitted to uterine curettage. The results of the histological examination revealed leiomyosarcoma. Staging workup showed an enlarged uterus with endometrial lesion, and non-calcified pulmonary nodules. The patient underwent a pan-hysterectomy and chemotherapy, and is under oncologic treatment. The authors call attention for the unusual form of presentation of this entity.

Co-infection of disseminated histoplasmosis and tuberculosis in an AIDS patient.

Histoplasmosis is a fungal disease caused by the dimorphic fungus Histoplasma capsulatum, recognized as an AIDS-defining illness since the Center for Disease Control's revision criteria in 1985. This infection is reported to be present in 5-20% of AIDS patients, and in 95% of the cases it is manifested in its disseminated form. Serum antibodies and/or antigen research can make diagnosis, but the demonstration of the agent by culture or histopathological examination remains the gold standard methods. Co-infections in patients with AIDS are well known; however, reports on disseminated tuberculosis and histoplasmosis are scarce. The authors report the case of a female patient who presented a short-course history of weight loss, fever, and mild respiratory symptoms, with hepatosplenomegaly and lymphadenopathy. Laboratory workup called attention to anemia, altered liver, canalicular enzymes, liver function tests, high titer of lactate dehydrogenase (LDH), and pulmonary nodules on thoracic computed tomography. Incidental finding of yeast forms within the leukocytes during a routine blood cell count highlighted the diagnosis of histoplasmosis. The patient started receiving amphotericin B but succumbed soon after. The authors emphasize the possibility of this co-infection, the diagnosis of severe infection through the finding of yeast forms within peripheral leukocytes, and for the high titer of LDH in aiding the differential diagnosis.

Hirschsprung's disease: the importance of early diagnosis.

Congenital intestinal aganglionosis, also called Hirschsprung disease (HD), is defined as the absence of ganglionic cells in the myenteric (Auerbach) and submucosal (Meissner) plexus, due to a failure in the enteric nervous system development. The extent of intestinal involvement may vary according to the age of embryo development in which this failure occurs. It is not unusual for other malformations to be present, as well as chromosomal trisomies, manly trisomy 21. Enterocolitis is a frequent, life threatening, and feared complication of HD. Moreover, oligohydramnios is a well-known condition frequently associated with malformations, including those related to the gastrointestinal tract. The authors report the case of a newborn that presented a delayed meconium passage. On the third day of life, he presented enterocolitis-the outcome of which was favorable with clinical treatment. While the diagnosis of HD was awaiting confirmation, the enterocolitis relapsed and this time he died due to septic shock. The autopsy findings were compatible with a short segment of congenital intestinal aganglionosis. No other malformation was found. The authors call attention for an early diagnosis of HD whenever the meconium passage does not happen for at least 48 hours and for the risk factors of enterocolitis. This case also demonstrates HD associated with oligohydramnios.

Is 2-mm punch biopsy useful in the diagnosis of malignant eyelid tumors?

PURPOSE: Two-millimeter punch biopsy is a swift and practical diagnostic tool in the outpatient setting. However, few studies have evaluated the efficacy of the method for diagnosis of malignant eyelid tumors. METHODS: This was an observational study of patients with suspicion of malignant eyelid tumor attending the Ocular Plastic Surgery Center at Hospital das Clínicas, University of São Paulo School of Medicine. Following standard procedures, preoperative biopsies were taken with a 2-mm trephine and surgical excision was performed with safety margins, followed by reconstruction. Anatomopathologic analysis of the surgical specimen was used as gold standard to evaluate the accuracy of diagnosis by punch biopsy. RESULTS: The study included 50 periocular tumors with suspicion of malignancy. The indicators of efficacy in the identification of malignancy by 2-mm punch biopsy were: sensitivity 88%, specificity 100%, positive predictive value 100%, and negative predictive value 64%. Accuracy was 90% for malignancy and 80% for histologic type. The κ index of agreement between the diagnostic methods was 0.722 (p < 0.001). CONCLUSION: A positive result with 2-mm punch biopsy is a safe indication for surgical excision of the tumor, whereas a negative result does not necessarily imply benignity. In cases of high clinical suspicion, a second biopsy should be taken from a different part of the tumor to rule out malignancy.

Nodular lymphocyte predominance Hodgkin lymphoma of the parotid gland: a case report.

The parotid is the most frequent site of primary salivary gland tumors. Lymphomas represent 0.2 to 0.8% of all malignant parotid tumors. Primary Hodgkin lymphoma of the parotid gland is rare with few cases reported in literature. The nodular lymphocyte predominance Hodgkin lymphoma (HL) is considered a particular clinical and histopathological subtype of HL. It has never been reported in the parotid gland since its incorporation in the 2001 World Health Organization Classification. The authors describe a case of a 32-year-old male who sought medical attention because of a one-year history of right cheek enlargement. A parotid nodule was submitted to a fine needle aspiration biopsy which disclosed a suspected lymphoproliferative disorder. A surgical dissection of the parotid gland was performed and an enlarged intraparotid lymph node measuring 4cm in its longest axis was excised, preserving the parotid gland integrity as well as the facial nerve. The pathological examination disclosed the diagnosis of nodular lymphocyte predominance Hodgkin lymphoma in this lymph node within the parotid gland. The treatment was completed with local radiotherapy and the 5-year follow up was uneventful.

Hemophagocytic lymphohistiocytosis of indeterminate cause: a fatal adult case.

Hemophagocytic lymphohistiocytosis (HLH) is an uncommon life-threatening disorder characterized by wide spread non-neoplastic proliferation and inappropriate activation of mature macrophages resulting in hypercytokinemia. This uncontrollable and ineffective systemic immune response causes fever, hepatosplenomegaly, cytopenias and subsequently multiorgan failure. The authors report a case of a 41-year-old male patient with a 30-day history of weight loss, fever, icterus, hepatomegaly, and cytopenias. The diagnostic workup disclosed hypertriglyceridemia, hypofibrinogenemia, and elevated ferritin. Bone marrow examination and clinical course raised the suspicion of HLH and treatment was started with high-dose corticosteroids and immune globulin. The patient underwent multi-organ failure and expired after 58 days of hospitalization. The autopsy finding included massive bone marrow infiltration by non-neoplastic histiocytes, many of them showing hemophagocytosis, which immunohistochemical study revealed diffuse CD68-positive histiocytes, which were negative for S100 protein. Hemophagocytosis was also observed in the lungs, lymph nodes and liver. The immediate cause of death was attributed to a massive intestinal bleeding due to extensive ischemic necrosis at the duodenum/jejunal transition area.

Hepatic necrosis associated with drug-induced hypersensitivity syndrome.

Drug-induced hypersensitivity syndrome (DIHS; also known as drug reaction with eosinophilia and systemic symptoms [DRESS]) is a life-threatening condition first described by Chaiken et al. in 1950. It is characterized by extensive mucocutaneous rash; fever; lymphadenopathy; hepatitis; hematological abnormalities; damage to several organs such as kidney, heart, lungs, and pancreas; and possible reactivation of human herpesvirus-6 (HHV-6) or other herpes virus. Rare and severe cases may present hepatic necrosis, and about 15% of them result in death or liver transplantation. A hallmark of this syndrome is the late onset of symptoms after the drug exposure. The most common culprit drugs are the aromatic anticonvulsants (in almost 30% of the cases) and the antibiotics (which in some series represent 20% of the cases). The authors report a case of a 41-year-old female who presented to the emergency department with erythroderma, acute hepatitis, acute pancreatitis and acute renal failure, and was then treated with corticosteroid after the diagnosis of DIHS/DRESS. A specific culprit drug could not confidently be determined due to the presence of multiple drugs used by the patient. The clinical and laboratory outcome was apparently satisfactory, but unexpectedly, on the sixth day of hospitalization, the patient complained of nonspecific malaise, drowsiness, which progressed in a few hours with signs and symptoms of hepatic failure, refractory shock, and death. The autopsy findings showed submassive hepatic necrosis, and the immediate cause of death was attributed to hepatic failure.

Strongyloides stercoralis disseminated infection and schistosomiasis in an AIDS patient.

Strongyloides stercoralis hyperinfection syndrome is classically associated with impaired host response and implies in an overburden of larvae in its usual cycle. It has been recognized as a severe and potentially fatal condition in immunocompromised individuals, especially those using oral corticosteroids. Infection with Schistosoma mansoni not only increases the susceptibility to HIV infection, but also promotes progression to disease. The association of the most severe forms of strongyloidiasis and AIDS is scarcely described, even more when S. mansoni is also associated. The authors describe a case of a 34-year-old previously healthy male, admitted to the emergency department with a history of hematemesis associated with dyspnea, hemoptysis, and fever. He referred homosexual relations for 6 years. Physical examination showed an ill-looking patient, and was remarkable for tachycardia, tachypnea, diaphoresis, and pulse oximetry of 70% in room air. Lungs examination revealed the presence of rales in the left base. Chest radiography showed a diffuse and bilateral reticulo-nodular pattern. HIV serology was positive. Empirical antimicrobial therapy and corticosteroids were initiated. On the third day of hospitalization, petechiae appeared over the periumbilical area, but no further investigation was undertaken because the patient died soon after. The autopsy findings were compatible with S. stercoralis disseminated infection, a hepatic intestinal chronic form of schistosomiasis, and septic shock as the primary cause of death. The authors call attention to this infrequent association.