Excessive Subchorionic Fibrinoid Deposition as a Component of Massive Perivillous Fibrin Deposition: A Case With Maternal Immune Thrombocytopenia

Maternal floor infarction (MFI) and massive perivillous fibrin deposition (MPFD) are overlapping placental disorders of unknown etiology, associated with adverse obstetric outcome, and a significant risk of recurrence. We describe a 31-year-old mother with asymptomatic thrombocytopenia throughout pregnancy and a positive lupus anticoagulant. She delivered a normal female neonate at term, whose weight was small for gestational age, with a placenta weighing less than the 10th percentile. Placental examination showed MPFD together with excessive subchorionic fibrinoid deposition. The placenta showed diffuse C4d deposition and an immune-mediated reaction was postulated for the pathogenesis of the placental changes. We suggest that excessive subchorionic fibrinoid deposition may be part of the morphologic spectrum of MFI/MPFD.

Disorder of Sex Development, Mosaic Genetic Disorder 45x, 46xy: A Case Report

Background. Disorder of sex development (DSD) is a congenital disorder associated with interference in chromosomes, gonads, or sexes anatomically. Individual affected with DSD can be recognized since birth due to external genital ambiguity. Sexual chromosome DSD occurred because sexual chromosome numeric or structural disorder. Mosaic karyotype 45X/46XY is among the rare sexual chromosome DSD with incidence less than 1:15,000 live births. DSD individuals are susceptible to stigmatization. This can cause stress, negative emotion, and social isolation. Therefore, DSD individual management should be done as optimal as possible. Case Presentation: Twelve years old girl complaining a bump arose from anterior side of her genital resembles male genital since 4 years prior to admission without micturition and defecation complains. Patient has not experienced menarche. On external genital examination, we found the normal female external genital such as mons pubis, pubic hair, labia majora, labia minora, hymen, perineum, but without clitoris which in this case it is replaced by a glans of penis, arising from anterior commissure of labia majora area, with an urethral estuary. Before the management is done, patient underwent multidiscipline consultations and further examinations. Subsequently, it was approved that the joint conference formation consisting obstetric and gynecology, urologist, and pediatric endocrinologist to determine the optimal management for the patient. Conclusion: In this case, diagnosis was made with history taking, clinical examination, and supporting investigation such as ultrasound imaging and could be followed by biochemistry test, voiding cystourethrography or genitogram to determine next management. Counseling should be done in detail towards the family to know what action is best for the patient. Multidiscipline team was required to get the optimum result either in medical, ethical, or religious point of view. Surgery in this case was considered followed by long term therapy afterwards.

Depot Pure GnRH Antagonist for Long-term Treatment of Ovarian Hyperthecosis Monitored by Multi-Steroid LCMS Profiling

Ovarian hyperthecosis (OHT), severe hyperandrogenism after menopause in the absence of ovarian or adrenal tumors, is usually treated by surgical excision. We report a 58-year-old woman presenting with severe hyperandrogenism (serum testosterone 15.7-31.0 nmol/L, normal female <1.8 nmol/L) with menopausal gonadotropins and virilization but no adrenal or ovarian lesions. Multi-steroid profiling by liquid chromatography-mass spectrometry (LCMS) of adrenal and ovarian vein samples identified strong gradients in left ovarian vein (10-30-fold vs peripheral blood in 17OHP4, 17 OHP5, A4, T, DHEA) but right ovarian vein could not be cannulated with the same findings in a second ovarian vein cannulation. OHT diagnosis was confirmed by an injection of a depot pure GnRH antagonist (80 mg Degarelix, Ferring) producing a rapid (< 24hr) and complete suppression of ovarian steroidogenesis as well as serum LH and FSH lasting at least 8 weeks with reduction in virilization but injection site reaction and flushing and vaginal spotting, ameliorated by an estradiol patch. Serum testosterone remained suppressed at 313 days after the first dose despite recovery of menopausal gonadotropins by day 278 days. This illustrates use of multi-steroid LCMS profiling for confirmation of the OHT diagnosis by ovarian and adrenal vein sampling and monitoring of treatment by peripheral blood sampling. Injection of a depot pure GnRH antagonist produced rapid and long-term complete suppression of ovarian steroidogenesis maintained over 10 months. Hence a depot pure GnRH antagonist can not only rapidly confirm the OHT diagnosis but also induce long-term remission of severe hyperandrogenism without surgery.

A CASE REPORT ON ANDROGEN INSENSITIVITY SYNDROME

Androgen Insensitivity Syndrome is an X linked disorder resulting in normal masculinization of external genitalia due to loss of function mutation in AR gene. Case Report : A 18 year old female presented with C/O not attaining menarche. Patient gives a history of lack of development of pubic and axillary hair. No history of abnormal breast development,cyclical abdominal pain or excessive weight gain. No relevant family history. O/E No palpable swellings in abdomen or bilateral inguinal region. External genitalia appear like a normal female external genitalia. The patient's karyotyping was done and it is of male genotype. The patient is diagnosed as Complete AIS as the phenotype is female and genetically male. The patient is managed by laparoscopic B/L orchidectomy with B/L deep ring closure.

Medical Management of Pyometra in the Delayed Postoperative Period

Pyometra is a rare condition in which purulent material becomes entrapped within the uterine cavity. If unrecognized in a timely fashion, life-threatening complications can arise. The following is a case report of a 50-year-old female who presented to the emergency department with abdominal pain and heavy vaginal bleeding. She was diagnosed with a pyometra based on imaging and treated conservatively with antibiotics. The patient ultimately had an uncomplicated hysterectomy with resolution of normal female pelvic anatomy prior to surgery. Pyometra should be considered when women present with diffuse abdominal pain or peritonitis. As demonstrated in this report, early detection and conservative management may help prevent serious complications such as uterine perforation, lead to shorter hospital stays, and result in safer operative management.

Female Hyperandrogenism in Elite Sports and the Athletic Triad

Essential hyperandrogenism seems to be overrepresented in female elite athletes. This applies to mild forms such as polycystic ovary syndrome, as well as rare differences/disorders of sex development (DSD). The reason is likely a selection bias since there is increasing evidence that androgens are beneficial for athletic performance by potent anabolic effects on muscle mass and bone mass, and stimulation of erythropoiesis. XY DSD may cause a greatly increased production of testosterone in the male range, that is, 10 to 20 times higher than the normal female range. The established regulations concerning the eligibility of female athletes with severe hyperandrogenism to compete in the female classification remain controversial. The most common cause of menstrual disorders in female athletes, however, is probably an acquired functional hypothalamic disturbance due to energy deficiency in relation to energy expenditure, which could lead to low bone mineral density and increased risk of injury. This condition is particularly common in endurance and esthetic sports, where a lean body composition is considered an advantage for physical performance. It is important to carefully evaluate endocrine disturbances and menstrual disorders in athletes since the management should be specific according to the underlying cause.

PSX-B-16 Recovery of live cells from refrigerated sheep skin after different days of cold storage

Cryopreservation of tissues from domesticated and wild relatives has been suggested to conserve genetic diversity. Ensuring that the tissues have live cells prior to preservation, especially in postmortem tissues, is an essential stem for success. How long cells live after clinical death is not precisely known in animals. The objective of this study was to evaluate the limits of cell survival in sheep skin stored at 4°C postmortem. Ear skin was procured from six random but healthy slaughtered animals and stored at 4°C in the lab. Ten explants (2–3 mm2) were cultured from each animal in DMEM media with 10% FBS, 50 units/mL of penicillin, 50 µg/mL of streptomycin, and 2.5 µg/mL of fungizone on two 60 mm dishes after 0, 10, 20, 27, 30, 35, 38, 41, 45, 50, 55, 60, 65 and 70 days of storage. Outgrowth of fibroblast-like cells around the explants was scored after 10 days of culture in a CO2 incubator. Results show outgrowth of cells up to 65 days of postmortem storage. Out of 476 explants adhered to dish surface, 374 (78.58%) exhibited outgrowth. The number of outgrowing cells decreased with increasing postmortem storage time interval. To test the differences between cell cultures obtained from postmortem fresh and stored tissues, we established secondary cultures from primary cells of 0-dpm and 65-dpm time points from selected cell lines. Both cultures exhibited similar growth morphology and growth curve, could be cryopreserved with >80% post freezing cell viability, lasted in cultures up to 35 passages, and expressed GFP gene upon transfection with a GFP gene containing plasmid vector. The karyotype analysis of 65-dpm tissue derived cells revealed a normal female karyotype without any genetic aberrations. These results suggest that normal proliferative cells can be recovered from sheep skin up to about 2 months postmortem, if kept refrigerated.

Therapy-Related Mixed Phenotype Acute Leukemia: Report of two cases with clinicopathological and molecular data

Introduction/Objective Therapy-related mixed phenotype acute leukemia (Tr-MPAL) is a rare and aggressive disease comprising blast cells of more than one hematopoietic cell lineage. There is limited patient outcome data with this diagnosis. Hence, we present two such cases with clinicopathologic correlation. Methods/Case Report Clinical and pathology data were obtained from institutional electronic health records for two cases of Tr-MPAL identified in the past three years (2018-2020). Results (if a Case Study enter NA) Case 1: 60-years old female, history of chemo-radiotherapy for breast carcinoma, had 49% circulating dimorphic blasts. By immunophenotype, blasts were positive for CD34, CD117, HLA-DR, cCD3, TdT, CD13, CD15, CD38, CD2, CD7, and MPO by cytochemistry, negative for B-cell lineage markers, consistent with Tr-MPAL, T/Myeloid. Ancillary studies revealed normal female karyotype, FLT3-ITD positivity, and DNMT3A frameshift mutation. The patient achieved remission with ALL regimen Hyper-CVAD/methotrexate-cytarabine and underwent an allogeneic stem cell transplant (SCT). The patient was disease-free and on maintenance therapy post 2 years of initial diagnosis. Case 2: 49-years old female, history of chemotherapy for breast carcinoma, had 77% circulating dimorphic blasts (MPO+/PAX5- and MPO-/PAX5+/CD79a+). By immunophenotype, blasts were positive for CD34, CD117, HLA-DR, CD13, CD33, CD15, CD11b, CD19+(dim), cytoCD79a(subset), MPO(subset) and negative for CD14, CD10, CD7, CD8, cCD3, cCD22, and TdT, consistent with Tr-MPAL, B/Myeloid. Ancillary studies revealed normal female karyotype, FLT3-ITD positivity, mutations in RUNX1(frameshift insertion S318fs), SETD2(frameshift insertion P1403fs), WT1(frameshift deletion T377fs), ATM (LI555H), CREBBP (P84S), and DNMT3A (W305). The patient was treated with ALL regimen Hyper-CVAD/methotrexate-cytarabine but relapsed in the post-induction phase with a similar genetics profile. Once remission was achieved, the patient underwent allogeneic SCT and is disease-free while on maintenance therapy post 18 months of initial diagnosis. Conclusion Phenotypically different Tr-MPAL also differ by their underlying genetic abnormalities and may vary in response to therapy. A large cohort of cases may provide us further insights into the genetics and survival outcome of this therapy-related leukemia subtype.

Valproic Acid Induced Thrombocytopenia and Dysmegakaryopoiesis in a Pediatric Patient

Introduction/Objective Valproic acid is a branched short chain fatty acid derivative that is used primarily to treat epilepsy as well as mood disorders, certain types of headaches, and neuropathic pain. It is commonly prescribed in the pediatric population and has shown to be effective for refractory epilepsy with adequate seizure control. Serious side effects may be prominent if the medication is not kept at the therapeutic range. A wide variety of known hematologic problems can be encountered including but not limited to anemia, thrombocytopenia, and leukopenia. Methods/Case Report We present a case of a pediatric patient with a past medical history significant for history of seizure disorder and who presented to Jackson Memorial Hospital for intermittent fevers and multiple unexplained bruises for 3 weeks as well as fatigue and weakness.The patient was recently started on valproic acid. Complete blood count (CBC) was obtained and showed a platelet count of 23 x10(3)/mcL with WBC of 3.5 x10(3)/mcL and hemoglobin of 9.7 g/dL.Serum valproate concentration was critically high (154 mg/L). Trephine biopsy showed a normocellular marrow (60%) showing maturing trilineage hematopoiesis and scattered atypical megakaryopoiesis characterized by small forms that are seen in relatively loose interstitial clusters (Figure 1). The marrow aspirate smears were characterized by cellular spicules with dysmegakaryopoiesis including numerous small hypolobated forms with frequent forms showing separated nuclei (Figure 2, 3, and 4). Blasts did not appear increased, comprising overall 1% of marrow cellularity. Karyotype studies revealed a normal female karyotype, 46, XX. FISH studies using probes commonly detected in MDS were negative. Next generation sequencing was negative for AML specific mutations including GATA1 and GATA2 mutations. Results (if a Case Study enter NA) N/A Conclusion This case report highlights the significant hematologic adverse effects of valproic acid, specifically pancytopenia with dysmegakaryopoiesis, raising the clinical suspicion of potential myelodysplastic syndrome. Critically high level of valproic acid (154 mg/L) and normalization of CBC after the stoppage of the medication strongly suggests that valproic acid can cause severe bone marrow suppression and specific morphologic atypia in the megakaryocytic lineage thus introducing a potential diagnostic pitfall. Because the CBC returned to normal, bone marrow biopsy was not repeated.