Coexistent Alpha-1 Antitrypsin Deficiency and Hereditary Hemochromatosis.

Alpha-1 antitrypsin (AAT) deficiency and hereditary hemochromatosis are systemic diseases inherited in an autosomal recessive fashion. The primary manifestation of AAT is early-onset pulmonary disease, while hemochromatosis primarily affects function of the liver, heart, and pancreas through excess iron deposition. No clear association between the two diseases has been delineated. We present a case in which a 34-year old female patient presenting with elevated liver enzymes during a visit for an unrelated acute illness was found to be a homozygous variant for AAT deficiency and hereditary hemochromatosis. A description of her presentation and clinical work up is included, along with a discussion of the epidemiology and clinical characteristics of each disease.

Squamous cell carcinoma of the cervix: a cytology-histology-human papillomavirus correlation in clinical practice.

CONTEXT: Cervical cancer mortality has declined by 74% in the United States since the implementation of the Papanicolaou (Pap) test. Nevertheless, more than 12,000 US women annually develop cervical cancer, and squamous cell carcinoma (SqCa) remains the predominant cervical malignancy. OBJECTIVE: To evaluate screening techniques used in the detection of SqCa of the cervix and provide insights regarding which technique(s) is (are) most efficacious in our study population. DESIGN: We retrospectively reviewed all available cytologic, human papillomavirus (HPV), and histologic malignancy burden data from patients diagnosed with SqCa. The clinical data were collected from 2 geographically and socioeconomically diverse hospital systems. Cases in which identified patients had a Pap test with a negative result/unsatisfactory specimen within 5 years of SqCa tissue diagnosis were considered Pap test screening failures. Cases in which patients were diagnosed with HPV-negative SqCa were considered HPV screening failures. RESULTS: Eighty-eight cases (patients' ages ranging from 19 to 73 years) were identified. Of those, cytologic history was available for 64 cases present in our electronic medical history record. Three cases were cytology screening failures (one being an unsatisfactory specimen) and 3 cases were HPV screening failures (one being the cytologic unsatisfactory case). Although measuring sensitivity in practice has limitations, we calculated the SqCa detection sensitivity at 95.3% by Pap test alone and 97% when HPV DNA testing was incorporated. CONCLUSIONS: Our results highlight the necessity of combining Pap and HPV testing. Although the number of cases identified is relatively small, our data suggest detection failures will decrease as the practice of combining HPV and Pap testing increases.

Glandular Lesions of the Cervix in Clinical Practice: A Cytology, Histology, and Human Papillomavirus Correlation Study From 2 Institutions.

CONTEXT: The Papanicolaou (Pap) test has indisputably decreased cervical cancer mortality, as rates have declined by up to 80% in the United States since its implementation. However, the Pap test is considered less sensitive for detecting glandular lesions than for detecting those of squamous origin. Some studies have even suggested an increasing incidence of cervical adenocarcinoma, which may be a consequence of a relatively reduced ability to detect glandular lesions with cervical cancer screening techniques. OBJECTIVE: To evaluate the detection rate of glandular lesions with screening techniques currently used for cervical cancer screening and to provide insight as to which techniques are most efficacious in our study population. DESIGN: We retrospectively reviewed any available cytology, human papillomavirus (HPV), and histologic malignancy data in patients diagnosed with adenocarcinoma in situ and adenocarcinoma from 2 geographically and socioeconomically disparate hospital systems. Identified patients having had a negative/unsatisfactory Pap test within 5 years of adenocarcinoma in situ or adenocarcinoma tissue diagnosis were considered Pap test screening failures. Patients with negative HPV tests on cytology samples were considered HPV screening failures. RESULTS: One hundred thirty cases were identified (age range, 22-93 years); 39 (30%) had no Pap history in our files. Eight of 91 remaining cases (8.8%) were screening failures. The detected sensitivity for identifying adenocarcinoma in situ/adenocarcinoma in this study was 91.2% by cytology alone and 92.3% when incorporating HPV testing. The most common cytologic diagnosis was atypical glandular cells (25 cases), and those diagnosed with adenocarcinoma were 7.4 years older than those diagnosed with adenocarcinoma in situ (50.3 versus 42.9 years). Nine of 24 HPV-tested cases (37.5%) were called atypical squamous cell of undetermined significance on cytology. CONCLUSIONS: Our results highlight the importance of combined Pap and HPV cotesting. Although the number of cases identified is relatively small, our data suggest screening for squamous lesions facilitates the recognition of glandular lesions in the cervix. Additionally, increased use of combined Pap and HPV cotesting may decrease detection failure rates with regard to glandular lesions.

Undifferentiated carcinoma of pancreas: a rare entity with aggressive behavior and possible genetic link.

UNLABELLED: An aggressive undifferentiated carcinoma of pancreas is a rare tumor, especially with a strong personal and family history of malignant melanoma. Limited literature review and few case reports described a genetic association between distinct types of pancreatic cancer and malignant melanoma. CASE REPORT: We present an uncommon case of an aggressive undifferentiated carcinoma of the pancreas in a 50-year-old Caucasian female. Initially, she presented with intermittent epigastric postprandial pain and mild nausea. A computed tomography scan of the abdomen showed a 5 cm heterogenous pancreatic tail mass, which on biopsy was found to be a poorly differentiated non-small cell carcinoma. Past medical history included malignant melanoma, with extensive family history of pancreatic cancer and malignant melanoma. However, not genetically confirmed, a hereditary pancreatic linkage was highly suspected. A week later, repeat computed tomography demonstrated tremendous enlargement of the pancreatic tail mass. Within a few weeks, the patient developed aggressive metastasis in various organ systems, followed by multiple surgeries. An emergent first round of chemotherapy was started, followed by an intensive care unit stay, and she eventually died. CONCLUSION: Our case exposes the aggressive behavior of undifferentiated carcinoma of pancreas, along with possible hereditary link between pancreatic cancer and malignant melanoma.

Verrucous carcinoma of the esophagus: a potential diagnostic dilemma.

Verrucous carcinoma of the esophagus is a rare variant of squamous cell carcinoma associated with human papillomavirus. We report the case of a 58-year-old female who presented with ongoing symptoms of dysphagia. On previous endoscopies she had been noted to have a large polyp-like mass involving the esophagus, with negative biopsies for malignancy. Repeat endoscopy with concurrent endoscopic ultrasound showed a large semi-pedunculated polyp in the distal esophagus and a hypoechoic, irregular mass involving the gastroesophageal junction with esophageal thickening. Deep layer biopsies showed pseudoepitheliomatous hyperplasia with immunohistochemical staining positive for human papillomavirus. The patient was subsequently treated with chemo-radiation followed by esophagectomy.

Sani-cloth wipe mimics rare enzyme deficiency malonic aciduria on newborn screen.

Within a 7-month period at our institution, newborn screening by tandem mass spectrometry revealed 10 cases with elevated levels of malonylcarnitine, which suggested malonic aciduria. Malonic aciduria is a rare autosomal recessive inborn error of metabolism. Confirmatory testing yielded normal results in all the newborns involved. The application of quality improvement practices dictated investigating the dried blood spot collection process, which revealed the use of multiple blood-collection techniques by newborn nursery staff, improper handling of the dried blood spot specimens, and sanitary wipe contamination as the causes of the aberrant false-positive results at our institution. This systematic evaluation identified the cause of the aberrant false-positive results and a strategy was implemented to avoid aberrant results in the future. Thus far, no false-positive results have occurred since the investigative process. False-positive results on a newborn screen can cause unnecessary emotional and economic stress on families, a finding that was identified at our institution. Historically, false-positive newborn screening results have been identified in infants born by cesarean delivery in which iodine antiseptic was used and in newborns who receive total parenteral nutrition, such as premature infants in the NICU. Therefore, if an unusually high number of false-positive results are found during the newborn screening process, contamination should be considered as a contributing factor.