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Tumor spread through air spaces (STAS) is associated with locoregional recurrence in patients undergoing limited resection (LR) for non-small cell lung carcinoma (NSCLC). We hypothesized that the observation of STAS in both the initial LR specimen and the additional resection specimen from the same patient, processed using different knives, would provide evidence that STAS is an in vivo phenomenon contributing to locoregional recurrence. We retrospectively identified patients with NSCLC (9 adenocarcinoma, 1 squamous cell carcinoma) who underwent LR, had STAS in the LR specimen, and underwent additional resection (lobectomy or LR). The LR and additional resection specimens from each patient were processed at different times using different tissue-processing knives. All specimens were analyzed for STAS. All 10 patients underwent LR with negative margins (R0). All additional resection specimens had STAS: 8 patients had STAS clusters in their completion lobectomy specimens, and 2 had STAS in their additional LR specimens. In 2 patients, STAS was found in the completion lobectomy specimen only after extensive sampling (>10 sections) from the staple line adjacent to the initial LR. The presence of STAS in both the LR and the additional resection specimen processed using different knives supports the concept that STAS is an in vivo phenomenon, rather than an artifact from tissue processing. This observation indicates that occult STAS tumor cells can be present in the lung tissue of the remaining unresected lobe after LR and supports the concept that STAS is a contributing factor for locoregional recurrence following LR., Competing Interests: Conflicts of Interest and Source of Funding: P.S.A.’s laboratory work is supported by grants from the National Institutes of Health (P30 CA008748, R01 CA236615-01, and R01 CA235667), the U.S. Department of Defense (BC132124, LC160212, CA170630, and CA180889), the Comedy versus Cancer Foundation, the Dalle Pezze Foundation, the Derfner Foundation, the Geoffrey Beene Foundation, the Memorial Sloan Kettering Technology Development Fund, the Miner Fund for Mesothelioma Research, the Mr. William H. Goodwin and Alice Goodwin, the Commonwealth Foundation for Cancer Research, and the Experimental Therapeutics Center of Memorial Sloan Kettering Cancer Center. D.R.J.’s laboratory work is supported by grants from the National Institutes of Health (R01 CA217169 and R01 CA240472). D.J.G. is supported, in part, by the National Institutes of Health (T32CA009501). For the remaining authors none were declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Thoracic myoepithelial tumors (MTs) are a rare group of tumors showing predominant or exclusive myoepithelial differentiation. They are poorly characterized from both a morphologic and genetic standpoint, in particular features that separate benign from malignant behavior. We examined the histologic and immunohistochemical features of 8 primary thoracic MTs and performed fluorescence in situ hybridization for EWSR1, FUS, PLAG1, and HMGA2, as well as several partner genes. Half (4/8) of the MTs occurred in large airways, and 3 had infiltrative borders. All cases showed immunoreactivity for epithelial markers, in conjunction with S100 protein or myogenic markers. MTs showed morphologic characteristics analogous to MTs at other sites, with no tumors having ductal differentiation. Necrosis and/or lymphovascular invasion was present in 5 cases, with mitotic activity ranging from 0 to 6 mitoses/2 mm² (mean 1). Metastases occurred in 2 cases, and no patients died of disease. Gene rearrangements were identified in half of the cases, with EWSR1-PBX1, EWSR1-ZNF444, and FUS-KLF17 fusions identified in 1 case each and 1 case having EWSR1 rearrangement with no partner identified. No cases were found to have HMGA2 or PLAG1 abnormalities. Compared with fusion-negative tumors, fusion-positive tumors tended to occur in patients who were younger (50 vs. 58 y), female (1:3 vs. 3:1 male:female ratio), and demonstrated predominantly spindle and clear cell morphology. Using a combined data set of our case series with 16 cases from the literature, poor prognosis was significantly correlated with metastases (P=0.003), necrosis (P=0.027), and ≥5 mitoses/2 mm²/10 high-power field (P=0.005). In summary, we identify a subset of thoracic MTs harboring rearrangements in EWSR1 or FUS, and our data suggest that necrosis and increased mitotic activity correlate with aggressive clinical behavior., Competing Interests: none

Thymic fibrosis in the absence of another primary thymic lesion, such as a neoplasm or cyst, is unusual. We identified 6 cases of primary extensive thymic fibrosis that developed in 3 men and 3 women, aged 28 to 60 years, mean 48 years. Patients had limited or no symptoms. Two patients had dyspnea and 1 had cough and hemoptysis. One female patient had myasthenia gravis. The lesions measured 3.5 to 17 cm in greatest dimension, mean 8 cm, and were confined to the anterior mediastinum as determined by imaging, intraoperative notes, and/or gross examination. All cases showed diffuse fibrosis with variable collagen deposition, lymphoplasmacytic infiltrates, and involution/atrophy of thymus. One case had rare IgG4-positive plasma cells and focal obliterative phlebitis. The histology showed overlap with that of IgG4-related sclerosing disease, which to our knowledge has not been documented earlier in this location. Although the etiology of the lesions is undetermined, altered immunity and/or infection may play a role.

Light chain deposition disease (LCDD) in the lung is a rare occurrence. We describe 5 new cases of this entity, review the literature, and compare pulmonary light chain deposits to pulmonary amyloidosis. In addition, we identified 17 patients with pulmonary LCDD in the literature with sufficient clinical information to allow evaluation of clinical presentation, laboratory findings, histologic appearance, and disease progression. In these 22 patients, 2 different histologic patterns were appreciated: diffuse and nodular. A parallel with the diffuse and nodular forms of pulmonary amyloidosis is suggested. The 10 patients with nodular LCDD had an overall better prognosis compared with the 12 patients with diffuse pulmonary LCDD. However, when compared to what is reported in the literature for nodular pulmonary amyloidosis, the patients with nodular LCDD had a higher incidence of an associated lymphoproliferative and/or plasma cell dyscrasia and renal failure. Light chain deposits in the lung are histologically similar to amyloid but are not Congophilic. Their electron microscopic appearance is distinctly different with fibrils in amyloid and granular deposits in LCDD. As the diffuse forms of LCDD and amyloidosis have a similarly poor prognosis, differentiating the 2 entities is probably not critical. However, when present as nodules, LCDD is more frequently associated with an underlying plasma cell dyscrasia or renal failure than is amyloidosis, and therefore the distinction may be clinically important.

We report 6 cases of low-grade pulmonary mucoepidermoid carcinoma displaying a striking lymphoplasmacytic infiltrate. All six tumors had a typical pulmonary mucoepidermoid carcinoma presentation as a polypoid endobronchial mass involving the proximal bronchi. The patients were 3 females and 3 males with a mean age of 33 years (range, 5-61 years). Half of the patients were asymptomatic, while half experienced mild symptoms of pneumonia, asthma-like symptoms, or hemoptysis. No tumor-related deaths were observed, with a mean follow-up of 51 months. The tumor size ranged from 2.1 to 3.4 cm (mean, 2.9 cm). The tumors characteristically displayed an elaborate tubulocystic epithelial component composed of intermediate, epidermoid, and mucus-producing cells, and variable numbers of clear cells, multinucleated giant cells, columnar cells, and oncocytic cells. The tumors' lymphoplasmacytic infiltrate with occasional Russell bodies was sufficiently intense to raise concern of a low-grade lymphoma. All tested tumors were immunoreactive with CK7 while nonreactive with TTF-1 and CK20. Recognition of this histologic variant is important for a correct diagnosis of low-grade pulmonary mucoepidermoid carcinoma. The dense lymphoplasmacytic infiltrate is similar to that previously described in salivary glands as tumor-associated lymphoid proliferation.

Separation of small cell lung carcinoma (SCLC) from nonsmall cell lung carcinoma (NSCLC) is a critical distinction to be made in the diagnosis of lung cancer. However, the diagnosis of SCLC is most commonly made on small biopsies and cytologic specimens, and practicing pathologists may not be familiar with all its morphologic guises and frequent combination with NSCLC elements, which may be seen in larger specimens. Following the most recent WHO classification of lung tumors and with the hope of identifying prognostic markers, we examined in detail the histology of 100 surgical biopsies or resections with a diagnosis of SCLC from the AFIP and pathology panel of the International Association for the Study of Lung Cancer (IASLC). Multiple clinical and histologic features were studied by Kaplan-Meier analysis. Neuroendocrine architectural patterns, including nested and trabecular growth, with peripheral palisading and rosette formation were common in SCLC. Necrosis and apoptotic debris was prominent in all cases, but crush artifact was infrequent. Cell size in surgical biopsy specimens appears larger than in bronchoscopic biopsy specimens and occasional cells may show prominent nucleoli and vesicular nuclear chromatin, but this does not preclude the diagnosis of SCLC. A high percentage of cases (28%) showed combinations with NSCLC, with large cell carcinoma the most common, followed by adenocarcinoma and squamous cell carcinoma. Because of the frequency of a few scattered large cells in SCLC, we arbitrarily recommend that at least 10% of the tumor show large cell carcinoma before subclassification as combined SC/LC. However, combined SCLC is easily recognized if the additional component consists of other NSCLC subtypes such as adenocarcinoma or squamous cell carcinoma, so no percentage requirement is needed. Stage remained the only predictor of prognosis.

To evaluate the usefulness of determinations of telomerase activity for distinguishing malignant from benign mesothelial lesions, immunohistochemical (using a rabbit polyclonal antibody and the peroxidase method; n = 68) and in situ hybridization (using sense and antisense oligonucleotide probes; n = 46) studies were made on malignant mesotheliomas (epithelioid, 39; sarcomatoid, 18, including 2 of the desmoplastic type; and biphasic, 11) and 19 benign mesothelial lesions (benign mesothelial hyperplasia, 3; and reactive pleuritis, 16). In addition, biochemical studies of telomerase activity were made in 9 of the malignant mesotheliomas. Telomerase activity was detected histochemically in all but one of the malignant mesotheliomas, but only in one (pleuritis) of the benign lesions, in which it was present only in activated lymphocytes. Antisense hybridization signals indicated the presence of telomerase mRNA mainly in the cytoplasm of the malignant cells. Sense probes gave negative results. Biochemical determinations revealed a strong telomerase activity in the 9 malignant mesotheliomas examined. This study demonstrates the usefulness of immunohistochemical staining for the evaluation of mesotheliomas. The required immunostaining can be performed using paraffin sections of formalin-fixed tissues.