Pseudosquamous Adenocarcinoma of the Lung: Clinicopathologic and Immunohistochemical Study of 10 Cases.

Pseudosquamous adenocarcinoma of the lung is an unusual morphologic variant of poorly differentiated non-small cell lung carcinoma that superficially resembles a squamous cell carcinoma. We have examined 10 cases of these tumors in 4 women and 6 men, aged 47 to 93 years. The tumors were all peripheral and measured from 1.5 to 5.5 cm. All cases were characterized by solid nests of large polygonal tumor cells containing atypical nuclei with abundant cytoplasm and sharp cell borders, adopting a pavement-like architecture that simulated squamous cell carcinoma. Some cases demonstrated intracytoplasmic hyaline inclusions suggestive of keratinization. The nests of tumor cells often showed central comedo-like areas of necrosis. Intercellular bridges were not seen in any of the cases. The tumors often displayed marked clearing of the cytoplasm enhancing their epidermoid appearance. In 4 cases, the solid pseudosquamous areas were seen to merge with a focal lepidic adenocarcinoma component, and in 1 case, abortive microscopic foci of acinar differentiation were also noted within the tumor. One case showed focal sarcomatoid spindle cell areas. The tumor cells were negative for p40 and CK5/6 and labeled with TTF1 or Napsin-A, confirming an adenocarcinoma phenotype. Clinical follow-up information was available in 8 patients; 6 patients died of their tumors between 6 months to 11 years after diagnosis (mean: 3.1 y). One patient died of complications related to surgery and one patient with a low-stage tumor died at 27 years from other causes. Solid pattern adenocarcinomas can be confused for squamous cell carcinoma and may require immunohistochemistry to determine their true phenotype.

Non-small cell lung carcinoma with clear cell features: a clinicopathologic, immunohistochemical, and molecular study of 31 cases.

Non-small cell lung carcinoma with predominantly clear cell features is a rare histologic presentation of lung carcinoma. We have examined 31 cases of lung carcinomas showing extensive clear cell features. The patients were 10 women and 21 men aged 47-92 years (mean: 70 years). The tumors showed a predilection for the right upper and lower lobes and measured from 0.8 to 9.5 cm (mean: 4.2 cm). By immunohistochemistry, 9 cases were typed as adenocarcinoma, 19 cases as squamous cell carcinoma, and 3 showed a "null" phenotype with complete loss of markers for adenocarcinoma or squamous cell carcinoma. Most cases that typed as adenocarcinoma showed a solid growth pattern. A subset of the solid adenocarcinoma cases showed a distinctive "pseudosquamous" morphology. Next-generation sequencing was performed in 20 cases and showed a variety of molecular alterations. The most common abnormalities were found in the TP53 gene (9 cases), FGFR gene family (8 cases), KRAS (5 cases), AKT1 (5 cases), and BRAF (3 cases). Clinical follow-up was available in 21 patients; 16/21 patients died of their tumors from 6 months to 12 years after initial diagnosis (mean: 4.2 years, median: 1.5 years). Four patients were alive and well from 4 to 27 years (mean: 11.5 years, median: 7.5 years); all were pathologic stage 1 or 2. NSCLC with clear cell features can display aggressive behavior and needs to be distinguished from various other tumors of the lung that can show clear cell morphology. The identification of targetable molecular alterations in some of these tumors may be of value for therapeutic management.

Successful Treatment of Eosinophilic Enterocolitis in an Adult Patient With Adalimumab.

Eosinophilic gastrointestinal diseases are increasing in prevalence, but understanding of their causes and effective treatments remain elusive, especially in adults. We present a case of eosinophilic gastroenteritis and colitis with extraintestinal manifestations that was successfully treated with a tumor necrosis factor α inhibitor, adalimumab.

Non-Small Cell Lung Carcinoma With Clear Cell Features and FGFR3::TACC3 Gene Rearrangement : Clinicopathologic and Next Generation Sequencing Study of 7 Cases.

Seven cases of primary lung tumors characterized histologically by clear cell morphology and a distinctive FGFR3::TACC3 gene rearrangement are described. The tumors arose in 4 women and 3 men, aged 47 to 81 years (mean=68). They occurred in peripheral locations, predominantly subpleural, and ranged in size from 1.4 to 6.5 cm (mean=4.1 cm). All tumors showed a solid growth pattern with abundant central areas of necrosis and marked nuclear pleomorphism. The tumors demonstrated clear cell histology, with large cohesive tumor cells displaying atypical nuclei and abundant clear cytoplasm. Immunohistochemical stains identified a squamous phenotype in 5 cases and an adenocarcinoma phenotype in 2 cases. One case was a squamous cell carcinoma with focal glandular component, and one of the squamous cell carcinomas showed focal sarcomatoid changes. Next generation sequencing identified FGFR3::TACC3 gene rearrangements in all 7 cases. One case demonstrated a concurrent activating FGFR3 mutation and a second case demonstrated concurrent FGFR3 amplification. Two cases harbored a concurrent KRAS G12D mutation. One case harbored both KRAS and EGFR mutations, and 1 case had a concurrent TP53 mutation. Non-small cell lung carcinoma harboring FGFR3::TACC3 gene rearrangements is extremely rare, and this rearrangement may potentially be enriched in tumors that demonstrate clear cell histology. Identification of FGFR3::TACC3 in patients with lung carcinomas with clear cell features may be of importance as they could potentially be candidates for therapy with tyrosine kinase inhibitors.

Oncocytic Follicular Cell-Derived Thyroid Tumors With Papillary Growth Pattern: A Clinicopathologic Study of 32 Cases.

CONTEXT.­: Oncocytic thyroid tumors displaying a papillary growth pattern are rare and may cause diagnostic problems. OBJECTIVE.­: To examine the clinicopathologic features of a series of 32 follicular cell-derived tumors composed of cells with oncocytic cytoplasm and displaying papillary architecture. DESIGN.­: Thirty-two cases were collected and studied to assess clinicopathologic features, including immunohistochemical and molecular testing for BRAF V600E. RESULTS.­: The patients were 26 women and 6 men, aged 17 to 77 years. The nodules ranged from 0.3 to 6.0 cm. Eighteen cases showed features of oncocytic hyperplastic nodules and were identified against a background of thyroid follicular nodular disease; 4 cases showed features of oncocytic follicular adenoma; and 10 cases corresponded to carcinomas with oncocytic and papillary features. Nuclear features of papillary thyroid carcinoma were absent or exceedingly rare. All cases were negative for HBME-1 and cytokeratin 19 (CK19) and wild type for BRAF V600E. Follow-up in 25 patients showed that all patients with hyperplastic nodules and oncocytic follicular adenomas were alive and well and free of disease from 7 to 20 years. One patient with oncocytic follicular carcinoma showed metastases and died of tumor at 16 months; 2 patients with carcinoma had metastases and recurrence at 6 and 7 years; and 5 patients with invasive tumors were free of disease from 5 to 10 years. CONCLUSIONS.­: Oncocytic thyroid tumors with papillary features can span a spectrum from benign hyperplastic, to encapsulated neoplastic, to invasive malignant lesions. Owing to their papillary features, it is important not to confuse them for other types of thyroid tumors, such as oncocytic papillary thyroid carcinoma.

Thymic Parenchymal Hyperplasia.

Thymic hyperplasia is a rare condition generally caused by lymphoid follicular hyperplasia associated with autoimmune disorders. True thymic parenchymal hyperplasia unassociated with lymphoid follicular hyperplasia is extremely rare and may give rise to difficulties in diagnosis. We have studied 44 patients with true thymic hyperplasia (38 females and 6 males) aged 7 months to 64 years (mean, 36 years). Eighteen patients presented with symptoms of chest discomfort or shortness of breath; in 20 patients, the lesions were discovered incidentally. Imaging studies demonstrated enlargement of the mediastinum by a mass lesion suspicious for malignancy. All patients were treated with complete surgical excision. The tumors measured from 3.5 to 24 cm (median, 10 cm; mean, 10.46 cm). Histologic examination showed lobules of thymic tissue displaying well-developed corticomedullary architecture, with scattered Hassall corpuscles separated by mature adipose tissue and bounded by a thin fibrous capsule. No cases showed evidence of lymphoid follicular hyperplasia, cytologic atypia, or confluence of the lobules. Immunohistochemical studies showed a normal pattern of distribution for keratin-positive thymic epithelial cells against a background rich in CD3/TdT/CD1a+ lymphocytes. Twenty-nine cases had an initial clinical or pathological diagnosis of thymoma or thymoma vs thymic hyperplasia. Clinical follow-up in 26 cases showed that all patients were alive and well between 5 and 15 years after diagnosis (mean, 9 years). Thymic parenchymal hyperplasia causing significant enlargement of the normal thymus that is sufficient to cause symptoms or worrisome imaging findings should be considered in the differential diagnosis of anterior mediastinal masses. The criteria for distinguishing such lesions from lymphocyte-rich thymoma are presented.

Pulmonary nodular elastosis: The intraparenchymal counterpart of pulmonary apical caps?

We have studied six cases in which focal consolidative pulmonary opacities observed on imaging studies led to surgical resection due to the suspicion of malignancy and showed on histopathologic examination a benign process characterized by an expansile tumor-like nodular accumulation of elastotic material. The patients were five women and one man aged 46 to 67 years (mean: 61 years). All lesions were found incidentally on imaging studies done for a variety of reasons, including surveillance for metastatic carcinoma in four patients. The lesions presented as solid nodules within lung parenchyma with irregular borders and spiculated margins and measured between 0.6 and 4.6 cm in diameter. Histological examination showed dense deposits of elastic tissue without evidence of malignancy, similar to those seen in pulmonary apical caps. Clinical follow-up between 5 and 16 years (mean: 10 years) showed that all patients were alive and well without evidence of disease. Pulmonary nodular elastosis is a localized intraparenchymatous process that may be confused clinically and radiographically for a malignant neoplasm and needs to be distinguished from other nodular lesions of the lung. To the best of our knowledge, tumor-forming lesions within lung parenchyma that are predominantly or almost exclusively composed of accumulation of elastic fibers have not been previously described.

Psammomatous calcifications in thyroid oncocytic (Hürthle cell) follicular tumors.

Concentric calcifications, also known as psammoma bodies, are a relatively frequent finding in certain types of tumors, particularly papillary thyroid carcinoma (PTC). In the thyroid, they have been assigned a significant role in the diagnosis of PTC and in distinguishing between these tumors and other types of thyroid neoplasms. Concentric calcifications have also less commonly been noted in other processes in the thyroid, such as in tumors characterized by cells containing abundant oxyphilic cytoplasm (i.e., Hürthle cells). We have studied 12 patients with oncocytic thyroid follicular tumors that contained scattered psammomatous calcifications that led to difficulties in diagnosis. The patients were 9 women and 3 men, aged 34 to 63 years. 10 cases corresponded to benign, non-invasive oncocytic tumors and 2 cases were minimally invasive follicular carcinomas of oncocytic (so called Hürthle cell) type. The psammomatous calcifications were randomly scattered throughout the lesions and were present as a focal, incidental finding in 8 cases and were diffuse in 4 cases. They were composed of concentrically laminated deposits of dense basophilic material closely resembling psammoma bodies, often associated with more homogeneous deposits of lightly eosinophilic material without concentric lamination that were interpreted as precipitated thyroglobulin. Seven patients with clinical follow-up, including one with minimally invasive carcinoma, were alive and well between 5 and 12 years after diagnosis. Concentric laminated calcifications may be encountered in oncocytic (Hürthle cell) follicular tumors and should not be interpreted as indicative of PTC in the context of oncocytic neoplasms of the thyroid.

A rare case of sebaceous lymphadenoma: Cytohistological correlation of preoperative cytomorphologic findings.

We are presenting a case of a 74-year-old female with a parotid gland mass. Fine-needle aspiration (FNA) of the mass demonstrated cohesive groups of epithelial cells with overall bland-appearing nuclei and abundant vacuolated cytoplasm, consistent with sebaceous cells, in a background of polymorphous lymphocytes, scattered histiocytes, and adipose tissue. Immunostains showed that the epithelial cells stain positive for p63, but negative for CD117 and DOG-1. CD3 and CD20 showed a mixture of T- and B-cells. On the PAP-stained slides, there were numerous sac-like structures, consistent with myospherules. These findings were suggestive of neoplasm with sebaceous differentiation. The main differential diagnosis included sebaceous adenoma, sebaceous lymphadenoma, and other benign lesions with sebaceous differentiation. The parotid mass was resected. Histology sections demonstrated a well-circumscribed neoplasm with multicystic epithelial component and surrounding lymphoid infiltrate, consistent with sebaceous lymphadenoma. Sebaceous lymphadenoma (SLA) is a rare benign salivary gland neoplasm that is most commonly seen in the parotid gland. Preoperative FNA diagnosis of sebaceous neoplasms is challenging. To the best of our knowledge, this is the third case of sebaceous lymphadenoma diagnosed preoperatively. In this manuscript, we detail the epidemiological characteristics and histogenesis of sebaceous salivary gland neoplasms, and the cytomorphologic differential diagnosis of SLA with key diagnostic features of each entity.

Oncocytic nodular hyperplasia of the thyroid.

Nodular hyperplasia of the thyroid is a process whereby the gland experiences growth by nodular expansion of thyroid parenchyma. We have encountered 45 patients in whom the process was caused by the growth of well-defined and sharply circumscribed but unencapsulated nodules composed of oncocytic thyroid follicular cells. The lesions arose in 39 women and 6 men, aged 25-69 years (mean = 50.3 years). The surrounding thyroid parenchyma showed features of chronic lymphocytic thyroiditis. The nodules varied from microscopic to 5 cm and appeared to compress the surrounding thyroid parenchyma. Most of the lesions lacked a well-defined capsule. In 26 tumors, the nodules displayed a predominantly follicular pattern of growth; in 8 cases there were admixtures of follicular and trabecular patterns with focal solid areas devoid of follicles. Clinical follow-up in 39 patients ranging from 7 to 22 years (median = 16 years) showed no evidence of recurrence, metastasis, or malignant transformation. One patient died of unknown causes 15 years after the diagnosis, and another patient died 4 years after diagnosis from metastatic colonic adenocarcinoma. Oncocytic nodular hyperplasia is a benign process associated with chronic lymphocytic thyroiditis that should be distinguished from benign and malignant oncocytic (Hurthle cell) tumors of the thyroid.

The value of 'raspberry bodies' in intraoperative cytologic evaluation of adnexal masses for the diagnosis of clear cell carcinoma of the ovary: A cytological-pathological correlation.

We report a case of a 48-year-old female who presented to the emergency department with pelvic/abdominal pain and a recent history of irregular periods. Pelvic ultrasound and computed tomography (CT) scan of the abdomen/pelvis revealed a 7.3 cm adnexal mass with suspicious features. During the intraoperative evaluation, a frozen section slide and a cytological smear were prepared. The cytological preparation was moderately cellular, showing cohesive groups of atypical cells with anisonucleosis, high nuclear to cytoplasmic ratio, and oval nuclei with prominent nucleoli. The tumor cells surrounded extracellular, magenta hyaline globules, forming raspberry bodies. Raspberry bodies are comprised of basement membrane deposits and are a unique finding in ovarian clear cell carcinoma. Raspberry bodies were also found in the frozen section slide, but, in comparison to the cytological preparation, were rare, difficult to identify, and resembled necrotic debris. The intraoperative diagnosis of a clear cell carcinoma is important because the surgical management will be more aggressive, as optimal tumor debulking is shown to have better overall survival. In this manuscript, we detail the intraoperative evaluation of an ovarian mass, the utility of cytological preparation and importance of identifying raspberry bodies in the evaluation of ovarian masses, and surgical management of clear cell carcinoma.

Histologic Patterns of Cutaneous Metastases of Breast Carcinoma: A Clinicopathologic Study of 232 Cases.

ABSTRACT: Cutaneous metastasis may be the initial sign of internal malignancy but more often represents a late manifestation of widely disseminated disease. Breast carcinoma is the most common malignancy to metastasize to the skin. Although several studies have detailed the histopathologic patterns of cutaneous metastasis from internal malignancies, very little has been published regarding metastases of breast carcinoma to the skin. Furthermore, the histopathologic and clinical features observed in the cases of breast carcinoma with local skin involvement as opposed to cases exhibiting distant cutaneous metastases have not been adequately investigated. We have reviewed 232 cases of breast carcinoma with cutaneous metastases from 2 large institutions. All cases of carcinoma of the breast with involvement of the skin of the anterior chest wall were compared with those with distant cutaneous metastases. Two hundred thirty-two cases in 199 patients were included, of which 126 had skin involvement exclusively involving the ipsilateral anterior chest, and 106 had biopsy-proven distant cutaneous metastases. Twelve patients had both local and distal spread. Distant cutaneous metastases showed a predilection for the contralateral anterior chest wall area, followed by the head and neck, back, and abdomen. Histologically, most of the tumors presented in this series showed features of infiltrating ductal carcinoma. In both ipsilateral and distant metastases, the tumors demonstrated little change in histologic features from the primary lesion; however, the distant metastases showed a tendency to display more poorly differentiated features. The mean patient survival when cutaneous involvement was localized to the skin of the anterior chest wall was 23 months as compared with 20.6 months when distant sites were affected. A comparison of the clinicopathologic features of the patients presented in this series suggests that alternate biological mechanisms may apply for local and distant skin metastases from breast carcinoma.

Diffuse interstitial pneumonia-like/macrophage activation syndrome-like changes in patients with COVID-19 correlate with length of illness.

OBJECTIVES: Assess the pathologic changes in the lungs of COVID-19 decedents and correlate these changes with demographic data, clinical course, therapies, and duration of illness. METHODS: Lungs of 12 consecutive COVID-19 decedents consented for autopsy were evaluated for gross and histopathologic abnormalities. A complete Ghon "en block" dissection was performed on all cases; lung weights and gross characteristics recorded. Immunohistochemical studies were performed to characterize lymphocytic infiltrates and to assess SARS-CoV-2 capsid protein. RESULTS: Two distinct patterns of pulmonary involvement were identified. Three of 12 cases demonstrated a predominance of acute alveolar damage (DAD) while 9 of 12 cases demonstrated a marked increase in intra-alveolar macrophages in a fashion resembling desquamative interstitial pneumonia or macrophage activation syndrome (DIP/MAS). Two patterns were correlated solely with a statistically significant difference in the duration of illness. The group exhibiting DAD had duration of illness of 5.7 days while the group with DIP/MAS had duration of illness of 21.5 days (t-test p = 0.014). CONCLUSIONS: The pulmonary pathology of COVID-19 patients demonstrates a biphasic pattern, an acute phase demonstrating DAD changes while the patients with a more prolonged course exhibit a different pattern that resembles DIP/MAS-like pattern. The potential mechanisms and clinical significance are discussed.

Metastatic atypical meningioma to the parotid gland - A cytopathological correlation.

The tumors involving the parotid gland are mainly primary, with metastatic lesions comprising only 5% of malignant salivary gland neoplasms. We are presenting a rare case of metastatic meningioma to the parotid in a 51-year-old male with a past medical history of recurrent atypical meningioma involving the frontal lobe. For the past 1.5 years, routine imaging showed parotid lesions with interval growth including a 2.0 cm dominant tender preauricular parotid mass. The chronicity and the number of lesions made malignancy unlikely. The differential diagnosis included non-specific lesions such as intraparotid lymph nodes and benign neoplasms. Fine needle aspiration of the parotid mass was performed to show loosely cohesive fragments and singly scattered neoplastic cells with mild nuclear pleomorphism and oncocytic cytoplasm. The main cytomorphologic differential diagnosis included oncocytic and myoepithelial-rich tumors. The neoplastic cells were immunoreactive to p63, calponin and SSTR2A and were negative for cytokeratins, progesterone receptor, S100, DOG-1, EMA, synaptophysin, and chromogranin. The cytology slides and the parotid gland mass resection were compared to the previous meningioma resection specimen which showed a similar morphology of the oncocytic tumor cells in some areas. The overall morphologic and immunohistochemical findings of the parotid tumor were consistent with metastatic meningioma. Extracranial metastases from intracranial tumors are extremely rare. Meningiomas arise from the dura matter, constitute 15% of primary brain tumors, and metastasize at an estimated rate of 0.1%. Despite how uncommon metastatic meningioma is, our case emphasizes the critical role of clinical history when evaluating parotid gland lesions.

FBN1 gene mutations in 26 Hungarian patients with suspected Marfan syndrome or related fibrillinopathies.

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder mainly affecting the cardiovascular, ocular and musculo-skeletal systems. FBN1 gene mutations lead to MFS and related connective tissue disorders. In this work we described clinical and molecular data of 26 unrelated individuals with suspected MFS who were referred for FBN1 mutation analysis. FBN1 gene sequencing was performed by next generation sequencing and Sanger sequencing methods. We identified 23 causal or potentially causal (including variants of uncertain significance) FBN1 variants, seven of them was novel (˜30%). About 30% of the cases were sporadic. FBN1 mutations were associated with MFS in the majority of the patients, in two cases with severe and early onset manifestation of the syndrome. Missense mutations were detected in 69.6% (16/23), the majority of them were located in one of the cbEGF motifs and ˜70% of them substituted conserved cystein residues. Small deletions/duplications were identified in 13% of the cases (3/23), while splice site variants were detected in 17.4% (4/23). In three unrelated patients a low frequency recurrent silent variant (c.3294C > T (p.Asp1098=) was identified. FBN1 mRNA analysis showed that the mutation does not lead to aberrant splicing, based on available data the mutation was classified as benign.

Small Cell Variant of Metastatic Melanoma: A Mimicker of Lymphoblastic Leukemia/Lymphoma.

It is well-known to pathologists that melanoma is "the great mimicker" and can look like anything. Despite this widespread awareness, the diagnosis remains a continuous challenge, especially when a metastatic melanoma with rare morphology is examined. We report a case of a 64-year-old man with a lung mass and right-sided pleural effusion who underwent video-assisted thoracoscopic surgery for pleural decortication. The history of melanoma was not reported to us. Microscopic examination revealed sheets of small round blue cells infiltrating into the adipose tissue in a lace-like pattern mimicking lymphoblastic lymphoma. Immunohistochemical stains for melanocytic markers, including S-100 protein, Mart-1, and HMB-45, highlighted the neoplastic cells. The tumor was also positive for CD56 and CD117, but negative for pancytokeratin, CD45, cytokeratin 8, TTF-1, WT1, CD34, chromogranin, synaptophysin, and neuron-specific enolase. The findings were most consistent with metastatic small cell melanoma, an uncommon variant of melanoma that closely resembles lymphoblastic lymphoma and other malignant small round blue cell tumors. To our knowledge, we are the first to describe a case of metastatic small cell melanoma to the pleura in an adult. Clinical and histological details are provided with a review of the literature.