Faculty Bibliography

Lung adenocarcinoma staging and grading were recently updated to reflect the link between histologic growth patterns and outcomes. The lepidic growth pattern is regarded as "in-situ," whereas all other patterns are regarded as invasive, though with stratification. Solid, micropapillary, and complex glandular patterns are associated with worse prognosis than papillary and acinar patterns. These recent changes have improved prognostic stratification. However, multiple pitfalls exist in measuring invasive size and in classifying lung adenocarcinoma growth patterns. Awareness of these limitations and recommended practices will help the pathology community achieve consistent prognostic performance and potentially contribute to improved patient management.

Programmed death-ligand 1 (PD-L1) expression in terms of the tumor proportion score (TPS) is the main predictive biomarker approved for immunotherapy against lung nonsmall cell carcinoma. Although some studies have explored the associations between histology and PD-L1 expression in pulmonary adenocarcinoma, they have been limited in sample size and/or extent of examined histologic variables, which may have resulted in conflicting information. In this observational retrospective study, we identified primary and metastatic lung adenocarcinoma cases in the span of 5 years and tabulated the detailed histopathologic features, including pathological stage, tumor growth pattern, tumor grade, lymphovascular and pleural invasion, molecular alterations, and the associated PD-L1 expression for each case. Statistical analyses were performed to detect associations between PD-L1 and these features. Among 1658 cases, 643 were primary tumor resections, 751 were primary tumor biopsies, and 264 were metastatic site biopsies or resections. Higher TPS significantly correlated with high-grade growth patterns, grade 3 tumors, higher T and N stage, presence of lymphovascular invasion, and presence of MET and TP53 alterations, whereas lower TPS correlated with lower-grade tumors and presence of EGFR alterations. There was no difference in PD-L1 expression in matched primary and metastases, although higher TPS was observed in metastatic tumors due to the presence of high-grade patterns in these specimens. TPS showed a strong association with a histologic pattern. Higher-grade tumors had higher TPS, which is also associated with more aggressive histologic features. Tumor grade should be kept in mind when selecting cases and blocks for PD-L1 testing.

Oral cancer causes pain associated with cancer progression. We report here that the function of the Ca²⁺ channel ORAI1 is an important regulator of oral cancer pain. ORAI1 was highly expressed in tumor samples from patients with oral cancer, and ORAI1 activation caused sustained Ca²⁺ influx in human oral cancer cells. RNA-seq analysis showed that ORAI1 regulated many genes encoding oral cancer markers such as metalloproteases (MMPs) and pain modulators. Compared with control cells, oral cancer cells lacking ORAI1 formed smaller tumors that elicited decreased allodynia when inoculated into mouse paws. Exposure of trigeminal ganglia neurons to MMP1 evoked an increase in action potentials. These data demonstrate an important role of ORAI1 in oral cancer progression and pain, potentially by controlling MMP1 abundance.

Tracheobronchial neoplasms are much less common than lung parenchymal neoplasms but can be associated with significant morbidity and mortality. They include a broad differential of both malignant and benign entities, extending far beyond more commonly known pathologic conditions such as squamous cell carcinoma and carcinoid tumor. Airway lesions may be incidental findings at imaging or manifest with symptoms related to airway narrowing or mucosal irritation, invasion of adjacent structures, or distant metastatic disease. While there is considerable overlap in clinical manifestation, imaging features, and bronchoscopic appearances, an awareness of potential distinguishing factors may help narrow the differential diagnosis. The authors review the epidemiology, imaging characteristics, typical anatomic distributions, bronchoscopic appearances, and histopathologic findings of a wide range of neoplastic entities involving the tracheobronchial tree. Malignant neoplasms discussed include squamous cell carcinoma, malignant salivary gland tumors (adenoid cystic carcinoma and mucoepidermoid carcinoma), carcinoid tumor, sarcomas, primary tracheobronchial lymphoma, and inflammatory myofibroblastic tumor. Benign neoplasms discussed include hamartoma, chondroma, lipoma, papilloma, amyloidoma, leiomyoma, neurogenic lesions, and benign salivary gland tumors (pleomorphic adenoma and mucous gland adenoma). Familiarity with the range of potential entities and any distinguishing features should prove valuable to thoracic radiologists, pulmonologists, and cardiothoracic surgeons when encountering the myriad of tracheobronchial neoplasms in clinical practice. Attention is paid to any features that may help render a more specific diagnosis before pathologic confirmation. ^©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Thyroid cytology has in recent years been augmented by molecular testing for indeterminate lesions. Three commercial molecular tests are available which provide variable amounts of detail regarding the genetic alterations identified in a sample. This paper will describe these tests, as well as the common molecular drivers associated with papillary thyroid carcinoma (PTC) and follicular patterned lesions, in order to help the practicing pathologist and clinician better interpret the results of these tests and incorporate this information into their management of cytologically indeterminate thyroid lesions.

Background: In mediastinal biopsies that show fibrosis, the differential diagnosis includes fibrosing mediastinitis, immunoglobulin G subclass 4-related disease, Hodgkin lymphoma, as well as reactive fibrotic and inflammatory changes adjacent to other processes including neoplasms. Cases Description: We report two cases of incidentally detected mediastinal seminoma that contained extensive areas of paucicellular fibrosis, which precluded accurate preoperative biopsy diagnosis. The fibrosis consisted of mildly inflamed, densely scarred tissue with thin dilated vessels, and was present to a significant extent that is suggestive of spontaneous regression. These features are not currently described in the World Health Organization Classification of Thoracic Tumors. In both patients, needle and open biopsies sampled only the fibrotic areas of the tumors, and the final diagnosis was not achieved until surgical excision was performed. After surgery, both patients received chemotherapy, and were alive without evidence of disease at 3.4 years and 1 year post-operatively, respectively. Tumor fibrosis composed approximately 95% and 50% of each patient"™s tumor, respectively. In one of the patients, correlation of the needle biopsy position with the positron emission tomography (PET) scan revealed that the biopsy needle had sampled a non-metabolically active portion of the tumor. Conclusions: While pathologic spontaneous regression is well-described in gonadal germ cell tumors, it is not well-reported in extragonadal locations. Prospective knowledge of this diagnostic pitfall and targeting PET-avid regions of the tumor may increase the diagnostic yield and help to avoid non-indicated surgical interventions.

In the version of this article initially published, Giampaolo Merlini (IRCCS Foundation Policlinico San Matteo, Pavia, Italy) was shown with an incorrect affiliation, which has now been corrected in the HTML and PDF versions of the article.