Allo-Anti-D vs. Auto-Anti-D in Females of Child Bearing Years: The Critical Role of Rh Genotyping

Introduction/Objective In females of child-bearing years, establishing accurate D-antigen identification is critical; this can be further complicated when a D+ patient seemingly develops an allo-anti-D. We present a unique case series highlighting the critical role of genotyping in distinguishing allo-anti-D vs. auto-anti-D. Methods/Case Report Case 1: An African American, 21-year-old, nulliparous female with a history of sickle cell disease presented for transfusion. The patient’s blood type was O, Rh Positive on multiple testing platforms (ORTHO VISION® Analyzer, 1001 US Highway 202, Raritan, NJ 08869, and Immucor, Inc., 3130 Gateway Drive, Norcross, GA 30071). On type and screen performed by manual tube testing, anti-D was identified. DAT IgG was weakly positive. The patient’s phenotype had been performed previously, and she was negative for both the C and E antigens. Genotyping results: RhD homozygote. RHD*DAU0 and RHD*DIVa type 3. The patient was determined to have auto-anti-D formation. Case 2 A 42-year-old female presented for routine prenatal care. At a previous facility, the patient tested as D+ and typed as O, Rh Positive (ORTHO VISION® Analyzer). An anti-D pattern was identified. Due to the patient’s Rh+ history and early pregnancy status, no Rh immune globulin was administered. A sample was sent to the reference laboratory which confirmed D+ status and a pattern of anti-D. The current titer was 8. Genotyping results RhD hemizyote. Positive for hybrid Rhesus box associated with deletion of RhD and RHD*DIVa, Go(a+). The patient was determined to have an allo-anti-D. Results (if a Case Study enter NA) NA Conclusion These two cases highlight the importance of RhD genotyping for resolutions of anti-D. In case 1, the patient had two altered alleles. While DIVa, type 3, is associated with anti-D formation, she also expressed RhD*DAU0 which is not considered to lack D proteins. We report the rare association between DAU0 expression and auto-anti-D formation.

Painless umbilical nodule in a nulliparous female – A clinical quandary

Background: Endometriosis is a well-known entity most often found within the pelvis and extra pelvic sites like skin, diaphragm, gastrointestinal tract and brain. Primary umbilical endometriosis is a rare form of cutaneous endometriosis, typically presenting as a hyperpigmented umbilical nodule with or without cyclical pain. We present a case of painless umbilical nodule with discolouration in a nulliparous woman, unsuspected clinically with the diagnosis being made primarily on cytology. Case report: A forty-year old female presented with a painless, brownish discoloured umbilical nodule, which was present since two months, was irreducible and had a negative cough impulse. She had no prior surgeries. Ultrasonography of abdomen and pelvis revealed a hypodense lesion of 2cm in the umbilicus, suggesting a possibility of umbilical granuloma. Uterus showed leiomyomata. Cytological evaluation of the umbilical nodule was suggestive of endometriosis. The patient underwent hysterectomy for leiomyomata and omphalectomy. Histopathology confirmed the diagnosis of umbilical endometriosis supported by the immunohistochemistry marker (CD10) being positive for endometrial stromal cells. The uterus had adenomyotic foci in addition to leiomyomata. Conclusion: The clinical distinction between primary umbilical endometriosis and other causes of umbilical nodules is challenging. Imaging modalities do not show pathognomonic signs in establishing this diagnosis. A definitive diagnosis is possible on cytology based on classical morphological features with histopathological examination being the gold standard diagnostic modality.

Leiomyosarcoma of Uterus in a Nulliparous Female: Mimicking as Ovarian Malignancy

Uterine sarcoma is a rare verity of smooth muscle tumor, accounting for 2 to 6% of uterine malignancies. Leiomyosarcoma (LMS) represents ~1% of overall uterine tumors and ~25 to 36% of uterine sarcomas. Here we present a case of uterine LMS in a 34-year-old nulliparous woman presented with huge distension of abdomen which was confused to be an ovarian malignancy. She underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. The diagnosis of LMS is made by histopathological examination after surgery. Surgery is the only treatment and role of adjuvant therapy has not been clearly defined.

Genetic interactions among Brca1, Brca2, Palb2, and Trp53 in mammary tumor development

Inherited mutations in BRCA1, BRCA2, and PALB2 cause a high risk of breast cancer. Here, we conducted parallel conditional knockout (CKO) of Brca1, Palb2, and Brca2, individually and in combination, along with one copy of Trp53, in the mammary gland of nulliparous female mice. We observed a functional equivalence of the three genes in their basic tumor-suppressive activity, a linear epistasis of Palb2 and Brca2, but complementary roles of Brca1 and Palb2 in mammary tumor suppression, as combined ablation of either Palb2 or Brca2 with Brca1 led to delayed tumor formation. Whole-exome sequencing (WES) revealed both similarities and differences between Brca1 and Palb2 or Brca2 null tumors. Analyses of mouse mammary glands and cultured human cells showed that combined loss of BRCA1 and PALB2 led to high levels of reactive oxygen species (ROS) and increased apoptosis, implicating oxidative stress in the delayed tumor development in Brca1;Palb2 double CKO mice. The functional complementarity between BRCA1 and PALB2/BRCA2 and the role of ROS in tumorigenesis require further investigation.