Chromophobe renal cell carcinoma (ChRCC) is a relatively rare subtype of RCC with a characteristic histologic appearance. Most ChRCCs are slow growing, but sarcomatoid differentiation and metastases ...can occur, indicative of aggressive behavior and poor prognosis. Herein, we characterize ten ChRCCs with aggressive components, defined as sarcomatoid change and/or metastasis. Immunohistochemistry (IHC) and next-generation sequencing were performed on available formalin-fixed paraffin-embedded tissue, with differential profiling of conventional and aggressive components. All ten cases showed a conventional component of renal tumor morphologically consistent with ChRCC: three had sarcomatoid change, four had metastases, and three had both sarcomatoid change and metastases. In the primary conventional components, a typical ChRCC IHC pattern (CK7+, CD117+, and CAIX-) was observed in 8 of 10 cases; 2 cases had rare CK7 staining. In the aggressive components, CD117 and/or CK7 was lost in 7 of 10 cases; 3 cases showed loss of both. Two of 10 cases showed significant CAIX staining in the aggressive component. All 7 cases that had molecular profiling performed showed characteristic chromosomal losses reported for ChRCC, with the aggressive components generally demonstrating more copy number complexity. Recurrent TP53 mutations (TP53m) were also seen; however, surprisingly, the conventional and aggressive components had no shared TP53m: a TP53m was private to aggressive components in 2 cases and to the conventional component in 1 case, and in 4 cases, components demonstrated different TP53m. Of the 21 pathogenic alterations identified in 7 tumors, only a PTEN splicing alteration was shared between both components in one case. In conclusion, ChRCC can have IHC staining patterns and molecular profile that differ between conventional and aggressive components. Interpretation of stains on metastases or small biopsies to determine histologic subtype can be misleading. The lack of shared pathogenic mutations between the two components supports a model in which aggressive ChRCC can have convergent subclones with different TP53m.
•Differential profiling of aggressive renal chromophobes shows lack of shared mutations•Chromophobes have intratumoral immunohistochemical and molecular heterogeneity•Interpreting stains or molecular data on metastases/small biopsies can be a pitfall
Abstract
Background
Key knowledge gaps remain in the understanding of viral dynamics and immune response of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection.
Methods
We ...evaluated these characteristics and established their association with clinical severity in a prospective observational cohort study of 100 patients with PCR-confirmed SARS-CoV-2 infection (mean age, 46 years; 56% male; 38% with comorbidities). Respiratory samples (n = 74) were collected for viral culture, serum samples for measurement of IgM/IgG levels (n = 30), and plasma samples for levels of inflammatory cytokines and chemokines (n = 81). Disease severity was correlated with results from viral culture, serologic testing, and immune markers.
Results
Fifty-seven (57%) patients developed viral pneumonia, of whom 20 (20%) required supplemental oxygen, including 12 (12%) with invasive mechanical ventilation. Viral culture from respiratory samples was positive for 19 of 74 patients (26%). No virus was isolated when the PCR cycle threshold (Ct) value was >30 or >14 days after symptom onset. Seroconversion occurred at a median (IQR) of 12.5 (9–18) days for IgM and 15.0 (12–20) days for IgG; 54/62 patients (87.1%) sampled at day 14 or later seroconverted. Severe infections were associated with earlier seroconversion and higher peak IgM and IgG levels. Levels of IP-10, HGF, IL-6, MCP-1, MIP-1α, IL-12p70, IL-18, VEGF-A, PDGF-BB, and IL-1RA significantly correlated with disease severity.
Conclusions
We found virus viability was associated with lower PCR Ct value in early illness. A stronger antibody response was associated with disease severity. The overactive proinflammatory immune signatures offer targets for host-directed immunotherapy, which should be evaluated in randomized controlled trials.
Polymerase chain reaction cycle threshold value ≤30 significantly predicts viral culture isolation, and increases with illness duration. Earlier seroconversion with higher peak immunoglobulin M/immunoglobulin G levels occurred in severe disease, as were higher levels of inflammatory markers, including interleukin-6 as a key interacting cytokine.
Oncocytic lesions of the thyroid are a heterogeneous group encompassing nonneoplastic and neoplastic entities ranging from benign to malignant and have traditionally been classified as separate ...entities in thyroid pathology. To illustrate the diversity of these thyroid lesions, we describe three cases of fine needle aspiration biopsies (FNAB) diagnosed as Bethesda Category IV: Follicular neoplasm, oncocytic type, under the 2017 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), with ThyroSeq v3 molecular testing and subsequent surgical excision.
Reconstruction of complex midfacial defects is best approached with a clear algorithm. The goals of reconstruction are functional and aesthetic.
Over a 15-year period (1992 to 2006), a single surgeon ...(P.G.C.) performed 100 flaps to reconstruct the following midfacial defects: type I, limited maxillectomy (n = 20); type IIA, subtotal maxillectomy with resection of less than 50 percent of the palate (n = 8); type IIB, subtotal maxillectomy with resection of greater than 50 percent of the palate (n = 8); type IIIA, total maxillectomy with preservation of the orbital contents (n = 22); type IIIB, total maxillectomy with orbital exenteration (n = 23); and type IV, orbitomaxillectomy (n = 19). Free flaps were used in 94 cases (94 percent), and pedicled flaps were used in six (6 percent).
One hundred flaps were performed in 96 patients (69 males, 72 percent; 27 females, 28 percent); four patients underwent a second flap reconstruction due to recurrent disease (n = 4, 4 percent). Average patient age was 49.2 years (range, 13 to 81 years). Free-flap survival was 100 percent, with one partial flap loss (1 percent). Five patients suffered systemic complications (5.2 percent), and four died within 30 days of hospitalization (4.2 percent). Over 50 percent of patients returned to normal diet and speech. Almost 60 percent were judged to have an excellent aesthetic result.
Free-tissue transfer offers the most effective and reliable form of reconstruction for complex maxillectomy defects. Rectus abdominis and radial forearm free flaps in combination with immediate bone grafting or as osteocutaneous flaps consistently provide the best functional and aesthetic results.
Therapeutic, IV.
Lymphedema is a chronic and progressive condition that occurs after cancer treatment. Autologous lymph node transplant, or microsurgical vascularized lymph node transfer (ALNT), is a surgical ...treatment option that brings vascularized vascular endothelial growth factor-C-producing tissue into the operated field to promote lymphangiogenesis and bridge the distal obstructed lymphatic system with the proximal lymphatic system. Operative techniques for upper- and lower-extremity ALNT are described with 3 donor lymph node flaps (inguinal, thoracic, cervical). Surgical technique is described for the combination of ALNT with abdominal flaps and nonabdominal flaps. Imaging showing restoration of lymphatic drainage after ALNT is shown.
Pathogenic DNM1L mutations cause a mitochondrial disorder with a highly variable clinical phenotype characterized by developmental delay, hypotonia, seizures, microcephaly, poor feeding, ocular ...abnormalities, and dysarthria. We report the case of an 8‐month‐old female with autosomal dominant, de novo DNM1L c. 1228G>A (p. E410K) mutation and mitochondrial disorder, septo‐optic dysplasia, hypotonia, developmental delay, elevated blood lactate, and severe mitochondrial cardiomyopathy leading to nonischemic congestive heart failure and cardiogenic shock resulting in death. This case suggests that cardiac involvement, previously undescribed, can be a clinically important feature of this syndrome and should be screened for at diagnosis.
Cytology cell blocks (CBs) are not routinely made for cerebrospinal fluid (CSF) specimens. The goal of this study was to identify when CSF CB preparation improves diagnostic performance.
Under ...institutional review board approval, a retrospective review of CSF cytology cases was conducted at a tertiary university-based hospital and an affiliated county hospital. Patient history, CSF volume, final diagnosis, use of stains, and whether the CB was contributory was determined from the cytopathology report. CSF nucleated cell count data was obtained from the medical record.
A total of 69 CSF specimens with CBs from January 2006 to March 2023 were identified from 61 patients. The median CSF volume was 8 mL (interquartile range, 4-13 mL; range, 1-800 mL), with immunohistochemical stains performed on 29 (42%) cases. Per cytology report, CB was contributory in 23 cases (33%), not contributory in 34 cases (49%), and not discussed in 12 cases (17%). The median volume was 8 mL for cases in which CB was contributory, not contributory, or not discussed. There was no difference in average nucleated cell counts between cases in which CB was contributory versus not contributory (73.9 vs. 40.0, p = .175).
CBs for CSF samples were contributory in a subset (33%) of cases. The authors were unable to identify any specific pre-analytic factors, including specimen volume and average nucleated cell counts, for cases in which CB was contributory. Further evaluation is needed to identify if there are scenarios in which CSF CBs should be routinely prepared.
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