Atypical Histopathological Aspects of Common Types of Lung Cancer-Our Experience and Literature Review.

Lung cancer is among the most common oncological diseases regarding incidence and mortality, with most of these having epithelial origins. Pathological reporting of these tumors is conducted according to the 5th edition of the World Health Organisation (WHO) classification of thoracic tumours. This study aims to draw the pathologist's attention to four rare, atypical microscopic aspects that some of the most common types of lung malignancies reveal upon standard evaluation (hematoxylin-eosin stain) that make histopathological diagnosis challenging: acantholytic, pseudoangiosarcomatous, signet ring cell, and clear cell features. Each of these aspects was exemplified by a case diagnosed in the pathology department of the "Marius Nasta" Institute. Furthermore, we analyzed the classification dynamics of different WHO editions and used PubMed to review articles written in English and published in the last eleven years on this subject. Pathologists should be familiar with these unusual aspects to avoid misdiagnoses and to ensure the correct classification of tumors, which is extremely important because these tumor phenotypes have been associated with specific molecular alterations and a worse clinical evolution. There is a need to clarify the histogenesis and associated genetic mutations, given the fact that the rarity of these tumor phenotypes makes their study difficult. Some authors consider these to be overlapping entities; however, we do not encourage this, as they may exhibit different prognoses and various molecular alterations with important therapeutic implications. The signet ring cell feature was associated with ALK rearrangement in lung adenocarcinoma; thus, these patients can benefit from tailored therapy with ALK-tyrosine kinase inhibitors (ALK-TKI). Recent studies associated clear cell morphology with FGFR3-TACC3 fusion, suggesting that patients with this diagnosis may be potentially eligible for FGFR inhibitors. We described, for the first time, the pseudoangiosarcomatous pattern in a case of lung adenocarcinoma; to our knowledge this aspect has only been described until now in the context of squamous cell carcinomas.

Navigating the Maze: Exploring Non-Oncological Complexities in Non-Small-Cell Lung Cancer.

Pulmonary oncological pathologies are an important public health problem and the association with other pulmonary lesions may pose difficulties in diagnosis and staging or require different treatment options. To address this complexity, we conducted a retrospective observational study at the Marius Nasta Institute of Pneumophthisiology, Bucharest, Romania. Our study focused on patients admitted in 2019 with non-small-cell lung carcinoma and associated pulmonary lesions identified through surgical resection specimens. Among the 314 included patients, multiple pulmonary nodules were observed on macroscopic examination, with 12% (N = 37) exhibiting nonmalignant etiologies upon microscopic examination. These findings underscore the challenge of preoperative staging. Patients with coexisting nonmalignant lesions were similar in age, smoking habits, and professional or environmental exposure by comparison with those who presented only malignant lesions. The presentation of coexisting malignant and nonmalignant lesions may pose difficulties in diagnosing and staging pulmonary cancer.

Lung cancer biomarker testing: perspective from Europe.

A questionnaire on biomarker testing previously used in central European countries was extended and distributed in Western and Central European countries to the pathologists participating at the Pulmonary Pathology Society meeting 26-28 June 2019 in Dubrovnik, Croatia. Each country was represented by one responder. For recent biomarkers the availability and reimbursement of diagnoses of molecular alterations in non-small cell lung carcinoma varies widely between different, also western European, countries. Reimbursement of such assessments varies widely between unavailability and payments by the health care system or even pharmaceutical companies. The support for testing from alternative sources, such as the pharmaceutical industry, is no doubt partly compensating for the lack of public health system support, but it is not a viable or long-term solution. Ideally, a structured access to testing and reimbursement should be the aim in order to provide patients with appropriate therapeutic options. As biomarker enabled therapies deliver a 50% better probability of outcome success, improved and unbiased reimbursement remains a major challenge for the future.

Large pleural tumor revealed by severe hypoglycemia: Doege-Potter syndrome.

AIM: Doege-Potter syndrome is a rare condition consisting of a mesenchymal tumor, either benign or malignant, accompanied by severe hypoglycemia. The syndrome was first described independently by two American physicians, Karl Walter Doege (1867-1932) and Roy Pilling Potter (1879-1968), in 1930, but it was not before 1988 that it was associated with non-islet cell tumor production of insulin growth factor (IGF) that induces hypoglycemia as a paraneoplastic syndrome. CASE PRESENTATION: We present the case of a 61-year-old woman with severe hypoglycemia that induced seizures. On the general check-up, a massive tumor occupying the lower part of left hemi-thorax was discovered. Initially, corticosteroids, glucose i.v. and high carbohydrate diet managed to prevent the severe blood glucose drop. Surgery exposed a massive well-defined pleural tumor. After surgical removal, blood glucose stabilized. Histological examination confirmed the fibrous tumor that proved to be malignant on immunochemistry. DISCUSSION: The authors discuss other cases reported in the literature of this rare condition and its pathogenic mechanisms, the presented case being the first reported in Romania. CONCLUSIONS: The clinician should be aware of the possible existence of a pleural tumor in a patient presenting an unexplained hypoglycemia because the surgical removal of the tumor can solve the clinical manifestations.

Respiratory bronchiolitis-associated interstitial lung disease - an unexpected form of idiopathic interstitial pneumonia in a young male.

Cigarette smoking is the most frequently encountered risk factor for chronic obstructive pulmonary disease and lung cancer. The latest American Thoracic Society÷European Respiratory Society classification of idiopathic interstitial pneumonia includes two entities related to smoking habits: respiratory bronchiolitis-associated interstitial lung disease and desquamative interstitial pneumonia. The new approach to diagnosis is to combine pathological pattern with clinical and radiological data. Lung biopsy is no longer considered the "gold standard" for diagnosis, but as a part of the diagnosis, which shall be set only after the pulmonologist, radiologist and pathologist reviewed all clinical, imaging and pathological aspects. We report a case of a young male, who complained of respiratory symptoms, had normal volumes and flows on lung function tests, moderately reduced transfer factor for carbon monoxide and "ground glass" attenuation on high-resolution computed tomography. Because the patient had exposure to contact with parrots, hypersensitivity pneumonitis was considered, but the broncho-alveolar lavage was without lymphocytosis. Open lung biopsy confirmed the diagnosis of respiratory bronchiolitis-associated interstitial lung disease, a rarely described entity in the medical literature. The patient had a good clinical outcome after smoking cessation.

Skin, ear and testis--unusual sites of tuberculosis.

Pulmonary localization is the most common site of tuberculosis (TB)and the most contagious form. Extrapulmonary tuberculosis with the rarest and most unexpected localizations represents a significant proportion of all cases of tuberculosis and remains an important public health problem. We report three unusual TB locations: skin, ear and testis occurred in three immunocompetent patients. In the case of skin and testicular lesions, diagnosis was based on pathological confirmation of granulomas with caseous necrosis. In the third case the diagnosis was made possible by identification of positive Acid-Fast Bacilli smear and positive culture from othic drainage fluid. The outcome at all three patients was good with antituberculous treatment. These unusual localization of tuberculosis also highlight the possibility of extrapulmonary tuberculosis as a differential diagnosis in many common diseases.

Nodular pulmonary amyloidosis--rare cause of calcified pulmonary nodules.

The article presents the case of a 60-year-old asymptomatic woman whose chest X-ray screening showed bilateral pulmonary nodules of uncertain etiology. Initially, the main suspicion concerned multiple pulmonary metastases, but the anatomical pathology examination of two of the surgically removed lung nodules revealed a benign pattern--foreign body granulomatous reaction to cholesterol crystals. Patient follow-up with a repeat computed tomography one year later showed that some pulmonary nodules had slightly increased in number and size, so the diagnosis required re-evaluation. Congo red staining revealed a positive reaction in the amorphous material, pointing to a nodular form of pulmonary amyloidosis. This case attests to the wide range of investigations needed to examine multiple pulmonary nodules and to the great variety of possible diagnoses. Surgical biopsy, alongside histopathological examination and immunohistochemical tests of the lung are critical in establishing a positive diagnosis. Pulmonary amyloidosis requires additional investigations and long-term follow-up of the patient, as this condition is frequently associated with MALT (mucosa-associated lymphoid tissue) lymphoma or multiple myeloma.

Synchronous primary lung cancer and controlateral pulmonary renal cell carcinoma metastases.

Synchronous malignant lesions will always entail treatment related difficulties which would ideally require discussions within a multidisciplinary committee in such a way as to reach the optimal solution for the patient. Presented herewith are two patients suffering from lung cancer and clear cell renal carcinoma contralateral metastases and the treatment alternatives that I have opted for.

Tissue prints for the rapid diagnosis of malignancy in lung cancer.

UNLABELLED: Rapid diagnosis of malignancy during oncological surgery is crucial for making decisions related to the extension of the resection. The tissue prints, used initially for plant biology but also for prostate or breast cancer diagnosis, might be useful as a rapid cytological diagnosis. MATERIALS AND METHODS: Tissue prints were done from freshly sectioned excised tissue fragments in patients operated between March 2010 and February 2012 in the Department of Surgery for cancer or benign lesions. Tissue prints were examined by a cytologist and considered as malignant or benign. Same fragments were then processed in the pathology laboratory using the typical paraffin-embedding method. All slides were examined by the same pathologist and considered the golden standard for malignancy and histological type. RESULTS: Three hundred and eleven fragments were examined, obtained from lung masses, lymph nodes, pleura and mediastinal masses, pathology showed 208 malignant and 103 benign. Tissue prints identified 227 malignant and 84 benign. For identifying malignancy, tissue prints had a sensibility of 0.91, specificity 0.64. Positive predictive value was 0.86 and negative predictive value 0.78. For lymph nodes, the specificity was better. In lymphomas and adenocarcinomas, tissue prints identified also the histology type in most cases. CONCLUSIONS: Tissue prints are rapid, easy to perform, cheap, with high sensibility but specificity lower than literature data on frozen sections. This might be improved by a better selection of cases where tissue prints are used for rapid diagnosis.

A rare case of lung tumor -- pulmonary inflammatory pseudotumor.

Pulmonary inflammatory pseudotumor (PIP) is a rare condition of unknown etiology. It is still a matter of debate if it represents an inflammatory lesion characterized by uncontrolled cell growth or a true neoplasm. Although mostly benign, these tumors are diagnosis and therapeutic challenges. Preoperative diagnosis can rarely be established. The treatment of choice is surgical resection which has both diagnostic and therapeutic value. We report the case of a 63-year-old male presented with clinical and imagistic picture suggestive of malignancy in the thorax. Lobectomy was performed with histological diagnosis of PIP. No evidence of tumor recurrence.

Unilateral pulmonary hilar tumor mass: is it always lung cancer?

Sarcoidosis is a multisystem inflammatory disease of unknown etiology, characterized by noncaseating epithelioid cell granulomas. In sarcoidosis, the most common radiological findings are mediastinal and bilateral hilar lymph node enlargement. We present a case of sarcoidosis with a rare radiological aspect of pulmonary hilar tumor mass.A 54-year-old female patient, active smoker (40 packs/year), with a history of cutaneous lupus, was admitted in our institute for progressive dyspnea and dry cough. At admission physical examination and laboratory tests were normal. Pulmonary function tests diagnosed an obstructive syndrome. Chest X-ray showed a tumor mass of the right pulmonary hilum. Transbronchial biopsy was nondiagnostic. HRCT-scan showed a tumor mass in the right hilum, which raised the suspicion of a lung cancer. PET-CT scan revealed a high metabolic activity of the tumor mass and of a paratracheal right lymphadenopathy. Lymph node biopsy by mediastinoscopy showed noncaseating epithelioid-cell granulomas, sustaining the diagnosis of sarcoidosis. The outcome was favorable, with spontaneous remission without treatment, but with a relapse that responded after systemic corticotherapy.In conclusion, even if a tumor mass in the pulmonary hilum is highly suggestive of lung cancer, a positive diagnosis should be made only after histological examination, because other benign conditions, like sarcoidosis, could have such an aspect.

[Practical issues of transbronchial lung biopsy (TLB) in pneumology]. / Biopsia pulmonara transbronsica--repere practice.

METHOD: We present a survey of 78 TLB which have been performed in Bronchology Service (during 2003-2005) for diffuse interstitial lung diseases--70 cases or located diseases--8 cases; TLB was not performed for solitary peripherally opacities because we have no radiological device with mobile arm (for good position of forceps). RESULTS: In 78% of cases we obtained illustrative lung tissue and in 22% of cases we prelevated just bronchial wall. Histological confirmation was obtained for 53% of cases; 47% of cases have as result lung tissue without significant modifications. Histological diagnosis was obtain in 41% of cases. The diagnosis of lung pathology was: diffuse lung fibrosis, tuberculosis, sarcoidosis stage II-III, malignant lymphoma, carcinomatosis, undifferentiated carcinoma, bronchioloalveolar carcinoma, squamous carcinoma, adenocarcinoma. There were 5 cases (6%) of small pneumothorax with spontaneous resorption and 11 cases with small bleeding (5-10 ml) who stopped spontaneously or at local administration of xilometasolin or oximetasolin. No other incidents were registered. CONCLUSIONS: TLB is a good alternative of surgical biopsy. The international guidelines request that the TLB has to be made before the thoracoscopy or the thoracotomy; because of the small size of prelevated fragments the diagnosis sensibility is variable. Our results for the 78 cases are comparable with the international data from literature both from the point of view of the diagnosis and the complications.