Concomitant gene mutations of MBL and CYBB in chronic granulomatous disease: implications for host defense.

Chronic granulomatous disease (CGD) is associated with defective function of the NADPH-oxidase system in conjunction with phagocytic defects which leads to granuloma formation and serious infectious complications. This is often associated with significant morbidity and mortality. The association of defective phagocyte function with other coincidental immune defects is unknown. Defects in innate pathways seen with CGD, including complement systems, and toll-like and dectin receptor pathways, have not been described before. We present the case of a 2-year old male patient hospitalized with recurrent pneumonia, a non-healing skin ulcer, necrotizing lung granulomas, and epididymo-orchitis. Defective neutrophil chemiluminescence was detected by dihydrorhodamine (DHR) testing. Further evaluation demonstrated characteristic molecular mutations of CYBB consistent with CGD. Immune evaluation demonstrated polyclonal hyperglobulinemia, but a greatly reduced mannose binding lectin (MBL) level. Six biallelic polymorphisms in MBL gene and its promoter were analyzed using Light CyclerTM Real-time PCR assay. The LXPA/LYPB haplotype of MBL was detected in our patient; the latter is the defective haplotype associated with low MBL levels. Due to the implications for innate immunity and the protection against bacterial, viral, and fungal infections provided by MBL, a deficiency of this protein may have disastrous consequences on the long term outcomes of CGD. MBL deficiency can also complicate other disorders affecting the immune system, significantly increasing the risk of infection in such patients. Further studies looking at the frequency and implications of MBL deficiency in CGD are needed.

ProExC triage of atypical glandular cells on liquid-based cervical cytology specimens.

OBJECTIVE: Morphologic distinction between atypical glandular cells not otherwise specified (AGC-NOS) and AGC-favor neoplasia (AGC-FN) can be difficult. Distinction between these entities is important as the American Society for Colposcopy and Cervical Pathology 2006 consensus guidelines state that management of AGC-NOS differs from that of AGC-FN. The objective of this study was to determine the potential role of ProExC immunocytochemical triage of AGC-NOS. MATERIALS AND METHODS: Cytopathology records from a pathology practice were reviewed from January 2006 to December 2009 to identify AGC-NOS liquid-based Pap smears with subsequent biopsy correlation. Archival slides were examined, and ProExC immunocytochemistry was performed. The AGC groups were assessed for nuclear staining, and results were correlated with subsequent biopsy findings. RESULTS: Twenty-eight AGC-NOS cases with biopsy correlation were identified: 13 with subsequent high-grade neoplastic or malignant (positive) diagnoses and 15 with benign diagnoses. Of 13 AGC-NOS cases with positive diagnosis, 10 were ProExC-positive and 3 were ProExC-negative (metastatic tumors from distant sites). Of 15 AGC cases with benign follow-up, 13 were ProExC-negative and 2 were ProExC-positive (sensitivity, 77%; specificity, 87%). For patients with cervical intraepithelial neoplasia or carcinoma originating from the female genital tract, 100% (10/10) were ProExC-positive (sensitivity, 100%; specificity, 87%). CONCLUSIONS: Results suggest that ProExC-positive AGC-NOS may be classified as AGC-FN. Although positive immunocytochemical staining for ProExC requires management similar to AGC-FN, negative staining does not rule out malignancy such as metastatic tumor. Management for ProExC-negative AGC-NOS cases should proceed according to the current guidelines for AGC-NOS.

Anaplastic thyroid carcinoma arising in long-standing multinodular goiter following radioactive iodine therapy: report of a case diagnosed by fine needle aspiration.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a highly aggressive, undifferentiated carcinoma that may arise on top of normal or abnormal thyroid. Making the diagnosis by fine needle aspiration (FNA) of the thyroid with a long-standing history of multinodular goiter (MNG) is not uncommon. We report a case discussing the cytopathologic findings and the relationship with long-standing goiter and thyroid exposure to radioactive iodine treatment. CASE: A 90-year-old male patient presented with a > 45-year history of MNG that was associated with thyrotoxicosis and multiple courses of radioiodine (I-131) treatment. He developed recent symptoms of dyspnea, dysphagia, neck welling and uniintentional weight loss. Computed tomography of the neck was done revealing a large MNG with retrosternal extension and calcifications. FNA was performed revealing highly anaplastic cells with a colloid background and presence of neutrophils. The diagnosis of ATC was made. The patient refused any kind of management and was discharged upon his request. He died 2 days after the procedure, and no autopsy was performed. CONCLUSION: ATC is an aggressive, undifferentiated thyroid carcinoma that can be diagnosed by FNA and save the patient a surgical intervention. A background of MNG and history of radioactive iodine therapy is not uncommon.

Strongyloides hyperinfection syndrome complicating (ectopic) Cushing syndrome.

Strongyloidiasis can present with a wide variety of symptoms and can lead to a potentially fatal hyperinfection. Although any factors that suppress the host defense mechanisms can potentially trigger hyperinfection, prolonged steroid use has been quite well described. A patient with disseminated small cell lung cancer suffered a Strongyloides stercoralis hyperinfection syndrome complicating ectopic adrenocorticotropic hormone (Cushing syndrome). Evaluation revealed lymphopenia, elevated levels of adrenocorticotropic hormone in the setting of elevated cortisol levels, a normal pituitary, and metastatic malignancy. S. stercoralis larval forms were seen in the stool and sputum. At autopsy, S. stercoralis larval forms were seen in the lung along with evidence of metastatic small cell lung carcinoma.