ABSTRACT
In patients with hematologic malignancies, multiparameter flow cytometry (FCM) offers greater sensitivity than cytology in detecting malignant cells in the initial cerebrospinal fluid (CSF) specimen. However, the role of FCM in assessment of subsequent specimens is unclear. We developed an algorithm to reduce the number of low-yield FCM tests without significant impact on clinically meaningful results. Patients with hematologic malignancies were studied in a derivation cohort, and the following algorithm was developed: (1) cytology and FCM on all initial samples, (2) cytology on all subsequent samples, and (3) FCM on subsequent samples only if previous FCM was positive. A separate population served as the validation cohort. The derivation cohort included 197 patients representing 1157 cytology and 543 FCM samples. Common malignancies were B-Cell ALL (25.3%), diffuse large B cell lymphoma (29.4%), and Burkitt lymphoma (7.7%). In the derivation cohort, the algorithm yielded a sensitivity of 90.0% (95% CI, 81.2-95.6%) and a specificity of 100% (95% CI, 98.9-100.0%). The validation cohort included 132 patients with 563 cytology and 602 FCM samples. In the validation cohort, the testing algorithm yielded a sensitivity of 87.5% (95% CI, 75.9-94.8%) and a specificity of 100% (95% CI, 99.1-100.0%). Of the 15 samples that were missed by the algorithm, FCM findings did not impact patients' management because of known CNS disease (seven patients) or they were responding to treatment (eight patients). CSF testing in hematologic malignancies using the proposed algorithm presents an evidence-based approach to reduce the number of unnecessary FCM tests of CSF without compromising patient care.
Subject(s)
Algorithms , Central Nervous System Neoplasms/diagnosis , Flow Cytometry/methods , Hematologic Neoplasms/cerebrospinal fluid , Hematologic Neoplasms/diagnosis , Adult , Aged , Cell Count/methods , Central Nervous System Neoplasms/cerebrospinal fluid , Central Nervous System Neoplasms/secondary , Cohort Studies , Cytodiagnosis , Female , Hematologic Neoplasms/pathology , Humans , Male , Middle Aged , Predictive Value of Tests , Sensitivity and SpecificityABSTRACT
Resistance to EGFR kinase inhibitors appears to be invariable in the treatment of non-small cell lung cancer. Several mechanisms have been described. Here, we report the first case of histologic transformation of EGFR mutant lung adenocarcinoma without prior exposure to EGFR inhibition.
Subject(s)
Adenocarcinoma/therapy , Carcinoma, Squamous Cell/diagnostic imaging , ErbB Receptors/genetics , Lung Neoplasms/diagnostic imaging , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adenocarcinoma of Lung , Aged , Carcinoma, Squamous Cell/genetics , Chemoradiotherapy , Disease Progression , Female , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Mutation , Sequence Deletion , Thoracic Surgical ProceduresABSTRACT
BACKGROUND: Lip metastases are rare clinical events that are frequently mistaken for other diagnoses. For sarcomatoid lung carcinoma, a rare histologic variant of non-small cell lung cancer, the incidence and pattern of cutaneous spread is poorly understood. CASE PRESENTATION: We present a case of a 79-year-old African American man with a rapidly progressive upper lip cutaneous lesion that provided the first evidence of distant metastatic spread of sarcomatoid lung carcinoma. CONCLUSIONS: This is the first reported case of lip metastasis in sarcomatoid lung carcinoma. It highlights the importance of maintaining a high level of suspicion for metastatic disease in the presence of new cutaneous findings as they may be the first evidence of advanced disease.
Subject(s)
Lip Neoplasms/secondary , Lung Neoplasms/pathology , Sarcoma/secondary , Aged , Fatal Outcome , Humans , Image-Guided Biopsy , Lip Neoplasms/radiotherapy , Lung Neoplasms/radiotherapy , Male , Sarcoma/radiotherapy , Tomography, X-Ray ComputedSubject(s)
Adenocarcinoma/pathology , Carcinoma, Squamous Cell/pathology , Genes, erbB-1/genetics , Aged , Female , HumansABSTRACT
Ovarian ectopic pregnancies are rare, with the majority diagnosed in the first trimester and often treated due to symptoms related to ovarian rupture. We report our experience with the diagnosis, management, and histologic evaluation of an unruptured second-trimester ovarian ectopic pregnancy. A 37-year-old woman presented with vague abdominal discomfort and irregular menses. Ultrasound detected a 16-week 4-day gestation with cardiac motion in the right adnexa and no evidence of an intrauterine pregnancy. Laparotomy with right salpingo-oophorectomy was performed, with removal of an unruptured pregnancy from the ovary. Although intraoperative examination and postoperative histopathologic evaluation demonstrated the classic Speigelberg criteria, it did not assist in the preoperative diagnosis, nor impact the treatment of the ovarian ectopic pregnancy in this case.
Subject(s)
Laparotomy , Ovariectomy , Pregnancy Trimester, Second , Pregnancy, Ovarian/surgery , Ultrasonography, Prenatal , Adult , Female , Humans , Pregnancy , Pregnancy, Ovarian/diagnostic imaging , Treatment OutcomeABSTRACT
OBJECTIVE: To evaluate the effect of myogenic stem cell-laden hydrogel scaffold on contractile function and histomorphology of the external anal sphincter (EAS) after transection without repair. METHODS: Eighty female rats underwent anal sphincter transection without repair. After 2 weeks, animals were injected at the transection site with: nothing (non-repaired control, NRC group); a polyethylene glycol-based hydrogel matrix scaffold combined with phosphate-buffered saline (PBS/hydrogel group); a hydrogel matrix scaffold combined with myogenic stem cells (stem cell/hydrogel group): or type I collagen (collagen) group. 4 (n = 40) or 12 (n = 40) weeks later, the anal sphincter complexes were dissected out and analyzed for contractile function, disruption, and striated muscle volume. Time-matched unoperated controls (UOC) were utilized for each of the two time points (n = 20). RESULTS: After 4 weeks, maximal electrical field-stimulated (EFS) contractions were significantly decreased in all four non-repaired treatment groups compared with UOC. However, EFS-stimulated contractions, tetanic force generation, and twitch tension were improved in non-repaired EAS injected with stem cell/hydrogel group relative to the NRC, PBS/hydrogel, or collagen groups. NRC and sphincters injected with PBS/hydrogel deteriorated further by 12 weeks, while those receiving stem cell/hydrogel maintained improved contractile function at varying frequencies and voltages. Striated muscle volume increased from 4 to 12 weeks for PBS/hydrogel and stem cell/hydrogel animals. At 12 weeks, stem cell/hydrogel animals had greater sphincter striated muscle volumes compared with all other treatment groups. CONCLUSION: In this animal model, sustained improvement of contractile responses in non-repaired EAS treated with biogel scaffold and myogenic stem cells suggests that a biologically compatible matrix may facilitate stem cell survival, differentiation, or function leading to recovery of contractile function even after persistent disruption.
Subject(s)
Anal Canal/surgery , Muscle Contraction/drug effects , Stem Cell Transplantation , Tissue Scaffolds , Wound Healing/physiology , Anal Canal/injuries , Anal Canal/physiology , Animals , Disease Models, Animal , Electric Stimulation , Female , Hydrogel, Polyethylene Glycol Dimethacrylate , Muscle Contraction/physiology , Muscles/cytology , Nanoparticles , Rats, Sprague-DawleyABSTRACT
Background. Patients with metastatic or radioactive iodine refractory papillary thyroid carcinoma (PTC) have poor prognosis due to ineffective therapy for this condition beyond surgery and radioactive iodine (RAI or (131)I). BRAF mutation occurs in more than 44% of PCT. Tyrosine kinase inhibitors, the most commonly used agents for these patients, have weak BRAF inhibition activity. BRAF inhibitors have demonstrated promising efficacy in relapsed metastatic PCT after standard treatment, though they are not currently approved for this indication. Case Presentation. We present the case of a 48-year-old Hispanic male who initially presented with columnar-cell variant subtype of PTC and positive BRAFV600E mutation. The patient had widespread bulky metastases to lungs, chest wall, brain, and bone. Discussion. Initial use of vemurafenib demonstrated a 42% cytoreduction of targeted pulmonary metastases and facilitated thyroidectomy and RAI treatment. The patient achieved a durable response over 21 months in the setting of widely metastatic disease. Conclusion. Vemurafenib may be effectively used for cytoreduction in patients with bulky metastatic PTC to bridge them to thyroidectomy and RAI treatment.
ABSTRACT
INTRODUCTION AND HYPOTHESIS: The objective was to evaluate the effect of myogenic stem cells on histological properties and the volume of striated muscle of the external anal sphincter after transection and repair. METHODS: Histological analysis was performed on the external anal sphincters of 40 young female rats euthanized at 7 or 90 days after transection and repair and randomization to injection of either phosphate buffered solution (PBS) or myogenic stem cells (SC) at the transection site. Sphincter complexes, previously evaluated for neurophysiological function, were processed for histology and analyzed for possible disruption, amount of inflammation, and volume of striated muscle. The relationship between the muscular disruption and contractile force of sphincters was evaluated. RESULTS: Disruption was seen in 100 % of sphincters 7 days after repair for both SC and control animals. Eighty-nine percent of controls and 78% of SC-administered animals had intact sphincters at 90 days. Significant inflammatory infiltrate was seen in repaired anal sphincters for both the PBS and the SC groups at 7 days, and persisted at 90 days, with no difference between treatment groups. Striated muscle volume increased from 7 to 90 days for both control and SC-administered animals. Although there was no difference in volume between treatments, there was substantial temporal improvement in contractile force generation of the sphincters receiving SC compared with those receiving PBS. CONCLUSION: In this animal model, administration of myogenic stem cells to transected/repaired anal sphincters did not alter the amount of inflammation nor the volume of striated muscle, suggesting that stem cells might improve contractile function through other cellular processes.
Subject(s)
Anal Canal/pathology , Muscle, Striated/pathology , Stem Cell Transplantation , Anal Canal/injuries , Anal Canal/physiopathology , Anal Canal/surgery , Animals , Female , Humans , Muscle Contraction , Muscle Strength , Muscle, Striated/physiopathology , Myositis/pathology , Organ Size , Rats , Rats, Sprague-Dawley , Wound HealingABSTRACT
INTRODUCTION AND HYPOTHESIS: Our purpose was to assess the accuracy of history and physical, cystourethroscopy, and magnetic resonance imaging (MRI) in preoperative diagnosis of urethral diverticula. METHODS: This was a retrospective review of all patients who underwent surgical excision of periurethral masses between 1998 and 2009. Presenting symptoms and examination and cystourethroscopic findings were noted. A single pathologist reviewed all cases and provided the reference standard for the diagnosis of a diverticulum. A single radiologist reviewed all preoperative MRI studies. Sensitivities, specificities, and positive and negative predictive values (PPV, NPV) were determined. RESULTS: Diverticula were diagnosed in 36/60 (60 %) patients. Transurethral fluid expression on palpation and recurrent urinary tract infection (UTI) had high PPV. Sensitivity, specificity, PPV, and NPV, respectively, for cystourethroscopy were 33 %, 100 %, 100 %, and 42 %; for MRI, these were 100 %, 83 %, 92 %, and 100 %. CONCLUSION: These data reinforce the utility of transurethral fluid expression for preoperative evaluation of urethral diverticula. Additionally, MRI is an excellent adjunctive diagnostic tool and may assist in establishing the diagnosis when there is high clinical suspicion of a urethral diverticulum but nonconfirmatory findings on cystourethroscopy.
Subject(s)
Cystoscopy , Diverticulum/diagnosis , Magnetic Resonance Imaging , Preoperative Period , Urethral Diseases/diagnosis , Adult , Diverticulum/pathology , Diverticulum/surgery , Female , Gynecologic Surgical Procedures , Humans , Middle Aged , Retrospective Studies , Sensitivity and Specificity , Urethra/pathology , Urethra/physiopathology , Urethra/surgery , Urethral Diseases/pathology , Urethral Diseases/surgery , Urologic Surgical ProceduresABSTRACT
Triple-negative (TN) breast carcinoma, characterized by estrogen receptor, progesterone receptor, and HER2 negativity, is a group of aggressive tumors that can be further classified into 2 subtypes: basal-like, defined as CK5/6 and/or epidermal growth factor receptor (EGFR) positive by immunohistochemistry; and non-basal-like. Clinical characteristics and tumor profiles were analyzed in 105 cases of TN tumors. Among these cases, 35 had distant metastasis, 34 had axillary nodal metastasis only, and 36 were nodal negative. Our results indicate basal-like TN breast tumors with nodal and distant metastases are significantly associated with a higher intratumoral expression of EGFR and CK5/6 compared to those in the nodal negative group. High level of intratumoral EGFR and CK5/6 expression may play a role in development of nodal or distant metastases in patients with basal-like TN tumors and may be predictive of metastatic disease. Furthermore, EGFR targeted therapy may be potentially useful in the treatment of basal-like TN breast cancer.
Subject(s)
Breast Neoplasms/metabolism , Carcinoma, Basal Cell/metabolism , ErbB Receptors/metabolism , Keratin-5/metabolism , Keratin-6/metabolism , Lymphatic Metastasis/pathology , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Carcinoma, Basal Cell/pathology , Female , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Middle AgedABSTRACT
Secondary (AA) amyloidosis is a disease that is caused by systemic deposition of amyloid fibrils. Circulating serum amyloid A protein is an acute phase reactant and levels are therefore high during inflammatory states. Chronic elevation of serum amyloid A levels results in accumulation and deposition in various organs, leading to organ dysfunction. Unless the inciting inflammatory state can be controlled, the subsequent development of amyloidosis diminishes patient survival. We report a case of systemic amyloidosis that presented primarily as chronic diarrhea in a patient with ankylosing spondylitis. Unfortunately for the patient, the diagnosis of amyloidosis was delayed for years despite encounters with multiple physicians. Early medical intervention to control chronic inflammation is imperative and could prevent morbidity and mortality related to the development of secondary amyloidosis. Consideration of amyloidosis as a diagnosis in patients who have chronic uncontrolled inflammatory conditions is also important in preventing poor outcomes related to this disease.
Subject(s)
Amyloidosis/complications , Amyloidosis/diagnosis , Diarrhea/etiology , Spondylitis, Ankylosing/complications , Amyloidosis/drug therapy , Antirheumatic Agents/therapeutic use , Humans , Male , Middle Aged , Spondylitis, Ankylosing/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitorsABSTRACT
Granular cell tumors are generally benign oncocytoid lesions of schwannian origin that are often incidental findings in many locations. Gastrointestinal stromal tumors occur in older adults and express the c-Kit protein (CD117). Both of these tumors have been described in association with many other entities; however, they have never been reported to occur jointly. This report is prompted by the simultaneous appearance of 2 granular cell tumors, a gastrointestinal stromal tumor, and a gastric adenocarcinoma in a 65-year-old woman with a history of breast carcinoma and granular cell tumor. To our knowledge, this is the first case report of these tumors occurring simultaneously.
Subject(s)
Adenocarcinoma/pathology , Gastrointestinal Neoplasms/pathology , Granular Cell Tumor/pathology , Neoplasms, Multiple Primary/pathology , Stomach Neoplasms/pathology , Stromal Cells/pathology , Adenocarcinoma/chemistry , Adenocarcinoma/surgery , Aged , Biomarkers, Tumor/analysis , Female , Gastrointestinal Neoplasms/chemistry , Gastrointestinal Neoplasms/surgery , Granular Cell Tumor/chemistry , Granular Cell Tumor/surgery , Humans , Immunohistochemistry , Neoplasms, Multiple Primary/chemistry , Neoplasms, Multiple Primary/surgery , Stomach Neoplasms/chemistry , Stomach Neoplasms/surgery , Stromal Cells/chemistryABSTRACT
BACKGROUND: Simple cysts of the female genital tract may become symptomatic and require surgical removal. CASE: A 20-year-old woman had complaints of a vaginal bulge, pelvic pressure, dyspareunia, and stress urinary incontinence. Two cystic masses were seen in the vagina. A magnetic resonance imaging scan revealed 2 additional larger cysts. Urodynamic evaluation was significant for stress incontinence at 200 mL and a Valsalva leak-point pressure of 51 cm H(2)0. The 2 smaller cysts were removed intact through a superficial incision. The larger cysts were intentionally ruptured and dissected out. Histologic examination revealed a low cuboidal or a ciliated columnar epithelium that stained positive with mucicarmine, consistent with müllerian origin. One year after surgical excision, the patient remained symptom free with no urinary incontinence and no recurrence of the cysts. CONCLUSION: Magnetic resonance imaging was useful in delineating the course and anatomic arrangement of the vaginal cysts, but more importantly, identified another cyst that was not readily apparent at physical examination.