COVID-19 and lung cancer.

COVID-19 pandemic had affected health services around the world, also reducing the diagnosis of lung cancer. On the other hand, examination of surgical specimens in patients with lung cancer and SARS-CoV-2 gave the opportunity to evidence early histologic features related to this emerging pandemic.Different prioritization of health organizations during COVID-19 pandemic resulted in a significant decline of lung cancer screening (up to 56%), delayed diagnosis (up to 30-40%) and higher advanced stage, with some exceptions (i.e., Canada). Increased use of stereotactic radiation treatments in stage I-IIA have been noticed in better-organized health systems. Surgical specimens performed for lung cancer in patients with incipient SARS-CoV-2 permitted to appreciate early histologic findings of COVID-19 with hyperplastic pneumocytes with/without fibrin exudate, alveolar macrophages/myeloid cells, perivascular T-lymphocytic infiltrate and lack of hyaline membrane.While the COVID-19 pandemic has declined the rate of lung cancer diagnosis worldwide, some institutions have significantly limited detrimental effects. Histology related to early SARS-CoV-2 infection in surgical samples for lung cancer revealed specific histologic changes.

Diffuse Pulmonary Meningotheliomatosis: Clinic-Pathologic Entity or Indolent Metastasis from Meningioma (or Both)?

Pulmonary minute meningothelial-like nodules (MMNs) are common incidental findings in surgical specimens, consisting of tiny proliferation (usually no larger than 5-6 mm) of bland-looking meningothelial cells showing a perivenular and interstitial distribution, sharing morphologic, ultrastructural, and immunohistochemical profiles with meningiomas. The identification of multiple bilateral MMNs leading to an interstitial lung disease characterized by diffuse and micronodular/miliariform patterns radiologically allows the diagnosis of diffuse pulmonary meningotheliomatosis (DPM). Nevertheless, the lung is the most common site of metastatic primary intracranial meningioma, and differential diagnosis with DPM may be impossible without clinic-radiologic integration. Herein, we report four cases (three females; mean age, 57.5 years) fitting the criteria of DPM, all incidentally discovered and histologically evidenced on transbronchial biopsy (2) and surgical resection (2). All cases showed immunohistochemical expression of epithelial membrane antigen (EMA), progesterone receptor, and CD56. Notably, three of these patients had a proven or radiologically suspected intracranial meningioma; in two cases, it was discovered before, and in one case, after the diagnosis of DPM. An extensive literature review (44 patients with DPM) revealed similar cases with imaging studies excluding intracranial meningioma in only 9% (4 of 44 cases studied). The diagnosis of DPM requires close correlation with the clinic-radiologic data since a subset of cases coexist with or follow a previously diagnosed intracranial meningioma and, thus, may represent incidental and indolent metastatic deposits of meningioma.

Diagnosis of Organizing Pneumonia with an Ultrathin Bronchoscope and Cone-Beam CT: A Case Report.

Organizing pneumonia (OP) is a pulmonary disease histopathologically characterized by plugs of loose connective tissue in distal airways. The clinical and radiological presentations are not specific and they usually require a biopsy confirmation. This paper presents the case of a patient with a pulmonary opacity sampled with a combined technique of ultrathin bronchoscopy and cone-beam CT. A 64-year-old female, a former smoker, was admitted to the hospital of Reggio Emilia (Italy) for exertional dyspnea and a dry cough without a fever. The history of the patient included primary Sjögren Syndrome interstitial lung disease (pSS-ILD) characterized by a non-specific interstitial pneumonia (NSIP) radiological pattern; this condition was successfully treated up to 18 months before the new admission. The CT scan showed the appearance of a right lower lobe pulmonary opacity of an uncertain origin that required a histological exam for the diagnosis. The lung lesion was difficult to reach with traditional bronchoscopy and a percutaneous approach was excluded. Thus, cone-beam CT, augmented fluoroscopy and ultrathin bronchoscopy were chosen to collect a tissue sample. The histopathological exam was suggestive of OP, a condition occurring in 4-11% of primary Sjögren Syndrome cases. This case showed that, in the correct clinical and radiological context, even biopsies taken with small forceps can lead to a diagnosis of OP. Moreover, it underlined that the combination of multiple advanced technologies in the same procedure can help to reach difficult target lesions, providing proper samples for a histological diagnosis.

Surgical Pathology of Diffuse Parenchymal Lung Disease in Patients With Psoriasis or Psoriatic Arthritis.

CONTEXT.­: Diffuse parenchymal lung disease (DPLD) is a well-recognized complication of systemic connective tissue disease (CTD) but rarely arises in patients with psoriasis or psoriatic arthritis, a poorly understood phenomenon. OBJECTIVE.­: To characterize DPLD associated with psoriasis or psoriatic arthritis, with or without prior immunomodulation. DESIGN.­: Pathology consultation files were searched for patients having psoriasis or psoriatic arthritis and DPLD. After excluding cases with active infection or smoking-related DPLD only, 44 patients (22 women; median age, 60 years; range, 23-81 years) were enrolled. Clinical history and pathology slides were reviewed. RESULTS.­: Twenty-seven of 44 patients (61%) had psoriatic arthritis; the remainder had psoriasis alone. Most presented many years later with nonspecific respiratory symptoms. Nearly one-third had no prior immunosuppression, and most had no concomitant CTD. Radiographically, ground-glass opacities, consolidation, and/or reticulation were typical. Histologically, nonspecific interstitial pneumonia and unclassifiable fibrosis were seen in 24 patients (55%) and 8 patients (18%), respectively; usual interstitial pneumonia and airway-centered fibrosis were rare. Superimposed acute lung injury was common, usually manifesting as organizing pneumonia. Lymphoplasmacytic infiltrates, lymphoid aggregates, and chronic pleuritis were frequent. Interstitial granulomas were seen in 17 patients (39%) but were usually rare, poorly formed, and nonnecrotizing. No histologic differences were apparent among patients with or without concomitant CTDs or prior therapy. CONCLUSIONS.­: Some patients with psoriasis or psoriatic arthritis develop clinically significant DPLD, even without prior therapy. Histopathologic findings mirror changes seen with other CTDs. Additional studies are warranted to clarify the association between psoriasis or psoriatic arthritis and DPLD.

What to Know About Biopsy Sampling and Pathology in Vasculitis?

PURPOSE OF REVIEW: To summarize the histologic findings of vasculitis, and to give some practical considerations on biopsy samples. RECENT FINDINGS: The larger use of imaging and the discoveries of serological markers in the diagnosis of vasculitis have increased the clinical recognition of these entities. Nevertheless, biopsy remains the gold standard for diagnosis in most cases. So far, biopsies are also useful to obtain information about prognosis and to guide a more specific treatment. In recent years, less invasive diagnostic approaches have become available, lowering the risks related to the procedure and permitting a definite diagnosis in most cases. Histological examination permits a definite diagnosis of vasculitis. However, the findings may be nonspecific if not evaluated in the proper clinical setting. The interaction between clinicians and pathologists is crucial to obtain a definite diagnosis.

Transbronchial Cryobiopsy in the Diagnosis of Diffuse Lung Disease.

Transbronchial cryobiopsy, a new diagnostic procedure in patients with diffuse lung disease, provides larger and better-preserved lung specimens compared to forceps biopsy. The diagnostic yield of cryobiopsy is much better than that of forceps biopsy and slightly lower than that of surgical lung biopsy, but with a lower complication rate compared to the latter. Literature suggests that in the multidisciplinary approach to patients with diffuse lung disease cryobiopsy provides diagnostic and prognostic information similar to surgical lung biopsy. Cryobiopsy can also be performed in some patients unsuitable for surgical biopsy, yet in whom histologic input is needed.

Cannonball-Like Lung Nodules in a Patient With a Colorectal Tumor.

CASE PRESENTATION: A 72-year-old man underwent endoscopic resection of a 10-mm polypoid sessile lesion of the rectum. Histologic examination found a well-differentiated, low-grade (G1), neuroendocrine tumor. A thoracoabdominal CT scan was performed for staging purposes. The chest CT scan revealed a so-called cannonball-like distribution of multiple rounded nodules, with well-defined margins, ranging from 0.5 to 5 cm, scattered in both lungs (Figs 1A, 1B). The abdominal CT scan showed no abnormalities. A recent colonoscopy showed no evidence of malignancy. No prior chest imaging was available and the patient had never complained of respiratory symptoms. The patient was a former smoker, with a smoking history of 20 pack-years. He had a history of hypertension, mild stenosis of both carotid arteries, and benign prostatic hypertrophy. He reported the presence of long-standing multiple cutaneous hemangiomas on the trunk and face and a larger hemangiomatous lesion on his left lower limb, which was previously investigated by color Doppler ultrasound imaging. All these lesions were reported as unaltered and unchanged since early infancy.

Diagnostic performances of 68Ga-DOTATOC versus 18Fluorodeoxyglucose positron emission tomography in pulmonary carcinoid tumours and interrelationship with histological features.

Few data are available about radio-receptorial positron emission tomography (PET) results by the use of 68Ga-DOTA-peptides in pulmonary carcinoid tumours. In this study, we retrospectively analysed 68Ga-DOTATOC/PET and 18Fluorodeoxyglucose (FDG) PET diagnostic performances in 62 pulmonary carcinoids (occurring in 57 patients) and interrelationship with histological features. All patients underwent at least 1 PET/computed tomography: 26 patients received 68Ga-DOTATOC, 52 patients had 18F-FDG and 20 patients received both techniques. There were 55 typical carcinoids and 7 atypical carcinoids. 68Ga-DOTATOC/PET recorded an 88.4% overall detection rate (DR) (meanSUVmax: 15.5); 18F-FDG/PET a DR of 53.8% (meanSUVmax: 3.2). When adopted a maximum standardized uptake value-threshold of 1.5, DRs of 68Ga-DOTATOC and 18F-FDG/PET increased to 100% and 80.8%, respectively. Moreover, DRs in both techniques vary considerably according to histology with 68Ga-DOTATOC/PET having better performances in typical carcinoids than in atypical carcinoids (DR: 91.7% vs 50.0%, P = 0.076). We also observed a significant correlation between a low number of mitoses (<2/10 high-power field) and 68Ga-DOTATOC/PET-positivity (P = 0.004), and an association trend (P = 0.076) between necrosis and 68Ga-DOTATOC/PET-negativity. In conclusion, 68Ga-DOTATOC had better diagnostic performances than 18F-FDG/PET in detecting pulmonary carcinoids. DRs of both techniques remarkably varied according to histology with 68Ga-DOTATOC/PET performing at its best in typical carcinoids, whereas 18F-FDG/PET did the same in atypical carcinoids.68Ga-DOTATOC/PET results were presumably associated with the number of mitoses and the presence of necrosis.

Primary classic Hodgkin lymphoma of the ileum and Epstein-Barr virus mucocutaneous ulcer of the colon: two entities compared.

Primary classic Hodgkin lymphoma of the gastrointestinal tract represents a rare occurrence. A full patient's work-up is essential in order to exclude a secondary intestinal involvement. Histologically Epstein-Barr virus mucocutaneous ulcer closely resembles Hodgkin lymphoma. The differential diagnosis between these two entities is relevant, since both the therapeutic approach and the clinical behavior are different. Herein, we describe a case of primary classic Hodgkin lymphoma arising in the ileum and a case of Epstein-Barr virus mucocutaneous ulcer of the colon, focusing on the main clinicopathological differences.

Intravascular NK/T-cell lymphoma, Epstein-Barr virus positive with multiorgan involvement: a clinical dilemma.

BACKGROUND: Intravascular lymphoma is a rare type of non-Hodgkin lymphoma mostly of B-cell lineage. A few cases of intravascular lymphoma have been found to be of NK/T-cell origin, mainly affecting the skin and central nervous system. CASE PRESENTATION: A 54-year-old Caucasian man sought care because of a 2 weeks history of jaundice and intermittent fever, not responsive to antibiotics and antipyretics. Laboratory tests showed low blood oxygen concentration and pancytopenia. Serum microbiological tests were negative. Computerized tomography (CT) scan revealed hepatosplenomegaly and diffuse ground-glass opacities in both lungs without interlobular septal thickening. Despite oxygen therapy, the clinical conditions rapidly deteriorated leading to death 3 days after admission. Autopsy revealed a multiorgan involvement by an Epstein-Barr virus positive NK/T-cell lymphoma, strikingly growing within the blood vessel lumina, in absence of skin lesions. CONCLUSIONS: The current case highlights the pathological features of this rare entity, the protean clinical presentation of which is often misleading, resulting in delayed diagnosis and treatment.

Cathepsin K expression in clear cell "sugar" tumor (PEComa) of the lung.

Clear cell "sugar" tumor is a rare benign neoplasm arising in the lung, considered as a part of the PEComa family. As PEComas of other sites, this tumor expresses melanocytic markers such as HMB45 and Melan-A. Despite cathepsin K, MITF and CD68 staining are known to be positive in a large number of PEComas and TFE3 rearrangement has been reported in a subset of PEComas, no data is available regarding the expression of these markers and the occurrence of TFE3 and TFEB rearrangement in clear cell "sugar" tumor of the lung. We have investigated the immunolabeling of cathepsin K, MITF, and CD68 in five cases of clear cell "sugar" tumor. Moreover, we have also sought the presence of TFE3 and TFEB rearrangement by fluorescence in situ hybridization (FISH) assay. In all tumors, strong immunoreactivity of cathepsin K and CD68 (PG-M1 and KP1 clone) was demonstrated, whereas none of them labeled for MITF staining and showed TFE3 or TFEB rearrangement. These findings widen the immunohistochemical profile of clear cell "sugar" tumor providing useful new markers for challenging cases. The expression of lysosomal markers, such as cathepsin K and CD68, strengthens the hypothesis that this tumor is part of the PEComa family.

Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH) Syndrome and Carcinoid Tumors With/Without NECH: A Clinicopathologic, Radiologic, and Immunomolecular Comparison Study.

The diagnostic criteria of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) are not well defined, and DIPNECH can be mistaken for carcinoids associated with neuroendocrine cell hyperplasia (NECH). In this study, we compared clinical, radiologic, histologic, immunohistochemical, and molecular features of DIPNECH and isolated carcinoids with/without NECH. The study population included 151 cases (77 female patients and 74 male patients), 19 with DIPNECH and 132 with carcinoids with/without NECH. None of the cases displayed molecular alterations or anaplastic lymphoma kinase expression. Compared with individuals with carcinoids with/without NECH, patients with DIPNECH were more likely to be female individuals (P<0.0001), nonsmokers (P=0.021), and symptomatic, and to have an obstructive/mixed respiratory defect, peripheral location of the lesions, and air trapping (P<0.0001) on chest computed tomography, and constrictive bronchiolitis on histology (P<0.0001). Among immunohistochemical markers, DIPNECH was associated with higher expression of thyroid transcription factor-1, CD10, and gastrin-releasing peptide/bombesin-like peptide (P<0.0001). Yet, when a purely histopathologic definition of DIPNECH was applied, 40% of isolated carcinoids also met the diagnostic criteria for DIPNECH, even in the absence of symptoms and/or radiologic abnormalities. Therefore, as DIPNECH represents a distinct clinical syndrome, we suggest the term DIPNECH be limited to cases presenting with respiratory symptoms, functional and/or radiologic abnormalities, and constrictive bronchiolitis on histology.