Cervical dysplasia in a patient with inherited epidermodysplasia verruciformis-A mere coincidence?

Epidermodysplasia verruciformis (EV) is a rare inherited or acquired genodermatosis caused by increased susceptibility to infection by the beta subtypes of human papillomavirus (HPV). The co-occurrence of EV with high-risk (HR) HPV infection leading to cervical dysplasia is unreported in the literature to date. We report a patient with inherited EV who developed extensive anogenital and cervical dysplasia linked to concurrent HR-HPV infection. Literature review suggests that there is a negative correlation of cervical dysplasia and cervical cancer with EV, which suggests that this patient's presentation and course are exceptional.

Pax2 expression in simultaneously diagnosed WHO and EIN classification systems.

PAX2 has been cited as a technically robust biomarker which nicely delineates precancerous lesions of the endometrium when the endometrial intraepithelial neoplasia (EIN) classification scheme is used. Its utility in distinguishing between atypical and nonatypical hyperplasia when applied within the 1994 World Health Organization classification system is questionable. The purpose of this study was to evaluate PAX2 in a side by side comparison of its staining patterns in a series of endometrial samples that were classified using both systems. A total of 108 precancerous endometrial cases were identified, of which 30 cases were deemed nonhyperplastic by consensus agreement and 11 cases lost the tissue of interest on deeper sections. The remaining 67 cases were categorized according to the 1994 World Health Organization criteria and EIN scheme by 2 gynecologic pathologists. PAX2 staining was scored in lesional tissue as normal or altered (lost, increased, or decreased) compared with nonlesional background. The most common pattern of alteration was complete loss of nuclear PAX2 staining (86.3%) followed by decreased staining (11.3%) and markedly increased staining (2.3%). PAX2 alterations correlated well with EIN diagnoses (33/36, 92%) compared with benign hyperplasia (2/13, 15%) but were less useful when the 1994 World Health Organization classification system was applied (PAX2 alteration in 22/25 (88%) of atypical hyperplasia cases versus 16/25 (64%) of nonatypical hyperplasia cases). Forty-five percent of follow-up hysterectomies with a previous PAX2-altered biopsy case harbored adenocarcinoma. In conclusion, PAX2 may be a helpful adjunct stain and training tool when the features of atypical hyperplasia/EIN are in question.

A novel use of a statewide telecolposcopy network for recruitment of participants in a Phase I clinical trial of a human papillomavirus therapeutic vaccine.

BACKGROUND: Historically, recruitment and retention of young women in intervention-based clinical trials have been challenging. In August 2012, enrollment for a clinical trial testing of an investigational human papillomavirus therapeutic vaccine called PepCan was opened at our institution. This study was an open-label, single-arm, single-institution, dose-escalation Phase I clinical trial. Women with recent Papanicolaou smear results showing high-grade squamous intraepithelial lesions or results that could not rule out high-grade squamous intraepithelial lesion were eligible to enroll. Patients with biopsy-confirmed high-grade squamous intraepithelial lesion were also eligible. Colposcopy was performed at the screening visit, and participants became eligible for vaccination when the diagnosis of high-grade squamous intraepithelial lesion was confirmed with biopsy and other inclusion criteria were met. The aim of this study was to identify strategies and factors effective in recruitment and retention of study participants. METHODS: Potential vaccine candidates were recruited through direct advertisement as well as referrals, including referrals through the Arkansas telecolposcopy network. The network is a federally funded program, administered by physicians and advanced practice nurses. The network telemedically links rural health sites and allows physician-guided colposcopy and biopsies to be conducted by advanced practice nurses. A variety of strategies were employed to assure good retention, including face-to-face contact with the study coordinator at the time of consent and most of study visits; frequent contact using text messaging, phone calls, and e-mails; and creation of a private Facebook page to improve communication among research staff and study participants. A questionnaire, inquiring about motivation for joining the study, occupation, education, household income, number of children, and number of sexual partners, was administered at the screening visit with the intent of identifying factor(s) associated with recruitment and retention. RESULTS: A total of 37 participants were enrolled between September 2012 and March 2014. The largest proportion of participants (46%) was enrolled from the telecolposcopy network. Others were enrolled through outside institutions (43%), in-house referrals (8%), or direct advertisement (3%). Most participants were motivated to join the study to take care of their health issues. Only two participants joined the Facebook private page. Of the 24 participants who qualified for vaccination, only 1 terminated early due to an unanticipated move. CONCLUSION: The availability of a large number of potential participants from the telecolposcopy network increased recruitment to this clinical trial by 85% over other traditional means of recruitment. The telecolposcopy network is not only a means of providing a gynecological service to women who otherwise would forego care but also a novel and valuable resource in recruiting participants for a clinical trial.

Left adrenal biopsy using the convex curvilinear ultrasound scope.

Effective use of the convex curvilinear ultrasound bronchoscope in the esophagus (EUS-B) is well described. EUS-B has not been described for diagnostic sampling of the left adrenal gland. We describe 6 cases of diagnostic fine-needle aspiration of the left adrenal gland using EUS-B. This capacity increases the diagnostic capabilities of the pulmonologist experienced in EUS-B.

Amyloid Light-Chain (AL) Amyloidosis of the Trachea Associated With an Indolent B-cell Neoplasm.

We report the case of a 66-year-old woman who was diagnosed with localized tracheal amyloid light-chain (AL) amyloidosis caused by an underlying B-cell neoplasm. The diagnosis was confirmed through subsequent bronchoscopy and biopsies; however, she experienced a challenging episode of hypoxic respiratory failure that required intervention. Repeat bronchoscopies showed persistent subglottic stenosis and tracheobronchomalacia, which led to tracheal debulking surgery and additional interventions. The patient's treatment began with rituximab, zanubrutinib, and dexamethasone with outpatient follow-up. The rarity of tracheobronchial amyloidosis and its connection to B-cell malignancies are highlighted, emphasizing the challenges in diagnosis and the importance of tailored treatment strategies. The patient's clinical course, characterized by atypical respiratory symptoms, delayed diagnosis, and an evolving treatment approach, underscores the complexities of managing such a rare and intricate case.

The spectrum of malignant diagnoses in cerebrospinal fluid cytology from an adult population: a multi-institutional retrospective review.

INTRODUCTION: Limited updated literature exists about the prevalence and spectrum of malignancies involving cerebrospinal fluid (CSF). In this multi-institutional study, we review our experience with focus on first time malignancy diagnosis in CSF samples of adults. MATERIALS AND METHODS: Institutional databases at 4 academic centers were queried retrospectively for CSFs over a 10-year period. The following data elements were collected: total # of CSFs, total # of CSFs with a malignant diagnosis; for each patient with a first time CSF diagnosis of malignancy: age, gender, diagnosis, prior history of malignancy, and ancillary studies. RESULTS: Twenty-four thousand one hundred forty-two CSFs were collected with a positive for malignancy rate of 2.3% (n = 551). Out of 347 (1.4%) adults with a first-time diagnosis of CSF malignancy 182 (52%) were female (age range: 19-89/mean: 57) and 165 (48%) were male (age range: 20-95/mean: 60). Hematolymphoid malignancies (48%, n = 168) were overall the most common neoplasm. In women, metastatic carcinomas (63%, n = 114) were the leading malignancy, of which the majority were breast primaries. In men, lymphomas/leukemias (64%, n = 106) were the leading malignancy, of which the majority were B-cell lymphomas. Ancillary studies aided the final diagnosis in 110 (32%) cases. For 286 (82%) cases, a prior history of malignancy was available to correlate CSF findings. CONCLUSIONS: A malignancy diagnosis in the CSF of adults is rare. The most common malignancies in females and males are metastatic breast carcinoma and hematolymphoid malignancies, respectively. Metastatic neoplasms account for the majority, with primary central nervous system neoplasms being quite uncommon. History of malignancy and ancillary tests can be helpful.

Expression of TLE1 in a Carcinoid Tumor of the Lung With Spindle Cell Morphology-A Potential Diagnostic Pitfall.

Tumors of the lung with a spindle cell morphology require consideration of many entities in the differential diagnosis, including metastases. Ancillary immunohistochemical stains but also molecular studies are typically required to arrive at the proper diagnosis. We present a case of a 71-year-old woman with multiple lung nodules, mediastinal lymphadenopathy, and a history of uterine cancer who underwent endobronchial ultrasound-guided fine needle aspiration and biopsy of the lung and mediastinal lymph nodes. A sampling of the lung lesion showed a cytologically bland neoplasm with spindle cell morphology, lacking necrosis or brisk mitotic activity. In conjunction with the cytomorphology, strong and diffuse Transducin-like enhancer of split 1 (TLE1) reactivity in the tumor cells initially raised the diagnosis of synovial sarcoma; however, subsequent results of additional testing showed strong and diffuse expression with AE1/AE3, CK 8/18, TTF-1, synaptophysin and chromogranin and focal or negative staining with a large number of other antibodies. This warranted a diagnosis of a carcinoid tumor. This is the first report of TLE1 staining in a carcinoid tumor of the lung. Therefore, when evaluating tumors of the lung with spindle cell morphology in which the differential diagnosis may include both carcinoid tumor and synovial sarcoma, TLE1 expression should be interpreted with caution and in conjunction with an expanded immunohistochemical staining panel.

The yield and impact of pulmonologist-performed EUS-B-FNA of subdiaphragmatic lesions-an institutional experience.

INTRODUCTION: Pulmonologists can biopsy structures below the diaphragm using the convex curvilinear ultrasound bronchoscope via the esophagus (EUS-B). The literature with respect to the value of EUS-B, rapid on-site evaluation, and final diagnostic yield for structures below the diaphragm is limited. We review our institutional experience. MATERIALS AND METHODS: Our database was queried retrospectively for EUS-B fine needle aspirations (FNAs) from 2013 to 2021. All procedures involving EUS-B-FNA of subdiaphragmatic structures were selected for analysis. The following data elements were collected for each patient: age, gender, clinical indication, sample site, on-site adequacy (OSA), preliminary and final diagnoses, and sufficiency of cell block for ancillary studies. RESULTS: A total of 75 subdiaphragmatic sites were biopsied in 74 patients. Of which, 87% of samples subjected to rapid on-site evaluation were deemed to contain adequate material (OSA+). There were no false-positive OSAs. Six cases remained nondiagnostic at the final diagnosis. The final diagnostic yield (with cell block) was 92% (69/75 cases). Cell block was sufficient for immunohistochemistry or special stains in all applicable cases (n = 36). Molecular testing was requested for 11 cases and successful in 10 (91%). Sampling of subdiaphragmatic sites changed the stage in 67% (38/57) of lung cancer patients. CONCLUSIONS: Pulmonologists can perform EUS-B-FNA of subdiaphragmatic sites with high OSA and final diagnostic yield when assisted by cytopathologists. Strong correlations exist between OSA, cell block adequacy, and subsequent capacity to perform ancillary testing. EUS-B below the diaphragm can make an important contribution to the diagnosis of lung cancer, nonpulmonary malignancies, and other diseases.

Blood banking and transfusion medicine for the apheresis medicine practitioner.

This article provides a concise overview of blood banking and transfusion medicine (BBTM) for the therapeutic apheresis medicine practitioner. It addresses the complete pathway from blood donor qualification to blood collection, to processing and storing blood components, to patient testing, to ordering blood components for therapeutic apheresis (TA) procedures, to preparing the component for transfusion, and finally to transfusion. The nurses, technologists, and physicians orchestrate these activities in concert to best serve patients undergoing TA procedures. Enhancing knowledge of these processes may improve the quality of patient care and the utilization of blood products.

A 34-Year-Old Man With Lightheadedness and Dyspnea.

CASE PRESENTATION: A 34-year-old man presented to our institution with lightheadedness and dyspnea on exertion. His medical history included chronic pancreatitis, juvenile rheumatoid arthritis (JRA), gastroesophageal reflux disease, hypertension, lumbar degenerative disc disease, seizure disorder, anterior uveitis, and multiple vertebral fractures. In addition, he was a cigarette smoker with a 10-pack-year smoking history.

Prospective Consensus Reporting by Gynecologic Pathology and Dermatopathology Improves Diagnosis of Vulvar Biopsies.

CONTEXT.­: Vulvar biopsy interpretation and reporting, particularly of vulvar dermatoses, can be challenging in daily practice for both surgical pathologists (SPs) and dermatopathologists (DPs). OBJECTIVE.­: To investigate whether prospective consensus reporting of vulvar biopsies by SPs and DPs would provide value and improve overall diagnostic concordance. DESIGN.­: Consecutive vulvar biopsies during a 6-month period were reviewed prospectively by both gynecologic SPs and DPs. Preliminary, independently generated diagnoses were recorded and then shared in consensus review (SPs+DPs). A third pathologist adjudicated cases without consensus. Multiple data elements were collected for each case: division (SP/DP), age, site, clinical history, diagnostic category, preliminary and final (consensus) diagnosis, need for adjudication, ancillary tests, and diagnostic discrepancy. RESULTS.­: Eighty-four biopsies (48 SP, 36 DP) from 70 patients were reviewed. Forty-two of 84 cases (50%) were neoplastic, 38 of 84 (45%) were reactive/inflammatory, with the remaining (5%) showing both or other features. Independent diagnoses were discrepant in 22 of 84 cases (26%), but consensus review resulted in an agreed-upon diagnosis in all cases, with adjudication required in 6 cases. Independent diagnostic agreement increased over time with a reduction in major and minor discrepancies between the first and second half of the study period. CONCLUSIONS.­: Prospective review of vulvar biopsies by both SPs and DPs can improve overall reporting. Consensus review allows pathologists to gain diagnostic confidence in interpretation of inflammatory (for SPs) and neoplastic (for DPs) vulvar biopsies; therefore, intradepartmental consultation is of value, particularly in select cases.

Signet Ring Cell Carcinoma with Lymphangitic Carcinomatosis in Pregnancy: A Case Report of an Unexpected Maternal Death and Review of the Literature.

BACKGROUND Cancer in pregnancy is extremely rare, and gastric cancers are rarer still. Diagnosis is difficult in pregnancy due to overlapping symptoms with pregnancy such as nausea, pain, anemia, and fatigue. CASE REPORT A 26-year-old G1 woman at 32 weeks gestation with a past medical history of systemic lupus erythematosus presented with new-onset chest pain and shortness of breath. Computed tomography of the chest, electrocardiogram, and echocardiogram were normal. Laboratory evaluation revealed thrombocytopenia, proteinuria of 480 milligrams, and normal complement. She delivered on hospital day 3 due to worsening chest pain. During cesarean delivery, the patient became hypotensive and hypoxic and required intensive care unit admission after a cesarean hysterectomy. On postoperative day 2 she had a pulmonary embolus and was started on therapeutic anticoagulation. She clinically improved until postoperative day 4, when she was found unresponsive with pulseless electrical activity. After 38 minutes of Advanced Cardiac Life Support, death was pronounced. An autopsy was performed and the cause of death found to be complications of multi-organ system involvement of adenocarcinoma with signet ring cell features. Lymphangitic carcinomatosis was noted throughout the lungs. CONCLUSIONS This patient had adenocarcinoma with signet ring cell features and associated lymphangitic carcinomatosis, which led to her postpartum death. Lymphangitic carcinomatosis is associated with an exceedingly poor prognosis, especially in pregnancy.

Accentuated p53 staining in usual type vulvar dysplasia-A potential diagnostic pitfall.

Evaluation of vulvar intraepithelial neoplasia (VIN) may be difficult due to overlapping histologic features seen in both usual (UVIN) and differentiated vulvar intraepithelial neoplasia (DVIN). DVIN represents a diagnostic challenge; poor inter-observer agreement is well documented. P53 has been described as a potentially helpful adjunct in some cases; however, intricacies in its interpretation remain. This study evaluated 41 consecutive cases which consisted of 23 keratinizing dysplasias that were morphologically suggestive of DVIN and 18 UVINs. All cases were stained with p16 and p53. Our results revealed that 22 of 41 (54%) VINs showed novel accentuated wild type (WT) staining with non-linear basal staining for p53, including 12 (52%) cases histologically suggestive of DVIN and 10 (56%) described as UVIN. P16 was positive in 100% of the accentuated wild type cases, consistent with a diagnosis of UVIN. Positive p53 and negative p16 staining was seen in 4 (17%) cases histologically suggestive of DVIN. Of these, 75% progressed to carcinoma, whereas only 1 of 35 (3%) patients with UVIN progressed to carcinoma. In conclusion, DVIN is difficult to diagnose due to potential histologic overlap with UVIN, especially the warty, or keratinizing, subtype. Accentuated WT p53 in absence of concurrent p16 staining may lead to misdiagnosis of DVIN, especially in small biopsy samples. P16/p53 staining should be performed in tandem with strict adherence to patterns considered positive, as patients with UVIN have significantly less risk of progression.

Diagnosis of lung tumor types based on metabolomic profiles in lymph node aspirates.

BACKGROUND: Treatment of lung cancer is evolving from the use of cytotoxic drugs to drugs that interrupt pathways specific to a malignancy. The field of metabolomics has promise with respect to identification of tumor-specific processes and therapeutic targets, but to date has yielded inconsistent data in patients with lung cancer. Lymph nodes are often aspirated in the process of evaluating lung cancer, as malignant cells in lymph nodes are used for diagnosis and staging. We hypothesized that fluids from lymph node aspirates contains tumor-specific metabolites and are a suitable source for defining the metabolomic phenotype of lung cancers. PATIENTS AND MATERIALS: Metabolic profiles were generated from nodal aspirates of ten patients with adenocarcinoma, ten with squamous cell carcinoma, and ten with non-malignant conditions using time-of-flight mass spectrometry. In addition, concentrations of selected metabolites participating in the kynurenine and glutathione pathways were measured in a second set of aspirates using tandem mass spectrometry. RESULTS: A list of consensus features that separated these three groups was identified. Two of the consensus features were tentatively identified as kynurenine and as oxidized glutathione. It was shown that metabolite concentrations in these pathways are different for patients with and without malignancy. CONCLUSION: Together the data suggest that metabolomic analysis of lymph node aspirates can identify tumor-specific differences in cancer metabolism and reveal novel therapeutic targets. This proof-of-concept study demonstrates the validity to complement and refine diagnosis of lung cancer based on metabolic signature in lymph node aspirates. MICRO ABSTRACT: Treatment of lung cancer is evolving from the use of cytotoxic drugs to drugs that interrupt metabolic pathways specific to a malignancy. We report here in that the metabolic phenotype of lung cancer can be determined in lymph node aspirates harboring malignant tumor cells. Knowledge about metabolic activity of malignant tumor cells may aide to personalize therapy.

Liquid biopsy and its role in an advanced clinical trial for lung cancer.

Liquid biopsy methodologies, for the purpose of plasma genotyping of cell-free DNA (cfDNA) of solid tumors, are a new class of novel molecular assays. Such assays are rapidly entering the clinical sphere of research-based monitoring in translational oncology, especially for thoracic malignancies. Potential applications for these blood-based cfDNA assays include: (i) initial diagnosis, (ii) response to therapy and follow-up, (iii) tumor evolution, and (iv) minimal residual disease evaluation. Precision medicine will benefit from cutting-edge molecular diagnostics, especially regarding treatment decisions in the adjuvant setting, where avoiding over-treatment and unnecessary toxicity are paramount. The use of innovative genetic analysis techniques on individual patient tumor samples is being pursued in several advanced clinical trials. Rather than using a categorical treatment plan, the next critical step of therapeutic decision making is providing the "right" cancer therapy for an individual patient, including correct dose and timeframe based on the molecular analysis of the tumor in question. Per the 21st Century Cures Act, innovative clinical trials are integral for biomarker and drug development. This will include advanced clinical trials utilizing: (i) innovative assays, (ii) molecular profiling with cutting-edge bioinformatics, and (iii) clinically relevant animal or tissue models. In this paper, a mini-review addresses state-of-the-art liquid biopsy approaches. Additionally, an on-going advanced clinical trial for lung cancer with novelty through synergizing liquid biopsies, co-clinical trials, and advanced bioinformatics is also presented. Impact statement Liquid biopsy technology is providing a new source for cancer biomarkers, and adds new dimensions in advanced clinical trials. Utilizing a non-invasive routine blood draw, the liquid biopsy provides abilities to address perplexing issues of tumor tissue heterogeneity by identifying mutations in both primary and metastatic lesions. Regarding the assessment of response to cancer therapy, the liquid biopsy is not ready to replace medical imaging, but adds critical new information; for instance, through a temporal assessment of quantitative circulating tumor DNA (ctDNA) assay results, and importantly, the ability to monitor for signs of resistance, via emerging clones. Adjuvant therapy may soon be considered based on a quantitative cfDNA assay. As sensitivity and specificity of the technology continue to progress, cancer screening and prevention will improve and save countless lives by finding the cancer early, so that a routine surgery may be all that is required for a definitive cure.

Well-Differentiated Neuroendocrine Tumor-A Low b-Grade Tumor's Aggressive Course and Dismal Outcome: A Case Report.

INTRODUCTION: Incidence of well-differentiated neuroendocrine tumors (NETs) of the colon and rectum is increasing and is now approximately 1 per 100,000 in the US. NETs are either well-differentiated (indolent) or poorly differentiated (aggressive). The majority of these tumors are found incidentally during screening colonoscopies and rarely are associated with symptoms of hormonal syndrome, even during the advanced stage. Metastatic well-differentiated NETs of the colon and rectum are incurable, hard to treat, and associated with a poor prognosis and survival rates similar to colorectal adenocarcinoma survival. CASE PRESENTATION: A 56-year-old man presented to our clinic with right-sided weakness and a 40-pound weight loss during the previous 2 months. A neurologic examination was remarkable for atrophy of the right trapezius muscle and decreased strength in the right upper extremity. Imaging revealed extensive blastic and lytic lesions involving the axial skeleton, a large rectal mass, a large necrotic nodal mass extending from the left iliac region to the level of the left renal veins, and multiple necrotic liver metastasis. Liver lesion fine-needle aspiration findings were consistent with metastatic well-differentiated neuroendocrine carcinoma. DISCUSSION: This case illustrates how a low-grade tumor can have an aggressive course with poor outcomes. Metastatic well-differentiated NETs of the colon and rectum remain difficult to treat because evidence is scarce. More research is needed on this topic.