Solitary pulmonary capillary hemangioma - An underrecognized rare tumor. Report of 32 new cases with literature review.

OBJECTIVE: To explore the clinical, imaging, pathologic characteristics and differential diagnosis of solitary pulmonary capillary hemangioma (SPCH). METHODS: Thirty two cases of SPCH were collected and studied, with literature review. RESULTS: This study included 13 males and 19 females, with a male-to-female ratio of 1:1.5. The age ranged from 26 to 70 years (median age of 43 years). All patients were asymptomatic at presentation. Lung nodules were incidentally discovered during chest computed tomography (CT). Imaging features included 21 cases with partial solid nodules (PSN), 7 cases with ground-glass nodules (GGN), and 4 cases with solid nodules (SN). Eleven cases were in the left lung lower basal segment, 11 cases in the right lung lower basal segment, 6 cases in the right lung upper anterior segment, and 4 cases in the right lung middle lateral segment. The lower basal segments of the lungs were involved in 22 (11 in each lung) cases (22/32, 68 %). The tumors ranged from 6 to 18 mm (average 10 mm). Macroscopically, 16 cases had clear boundaries, while 16 cases had unclear boundaries, and gray-red or dark brown on cut surfaces. Intraoperative frozen section was performed in 27 cases, with diagnosis of SPCH in 12 and pneumonia or inflammatory lesion in 15. Microscopically, the nodules were composed of densely proliferated and dilated capillaries. The capillary walls were lined with a single layer of flat endothelial cells, without atypical features. Collapsed alveolar septa were replaced by a large number of capillaries. All cases showed proliferating capillaries spreading into the walls of small veins/arteries and bronchi, with 3 cases showing dilated capillaries protruding into the bronchiolar lumens as polyp-like structures. Twenty-six cases (26/32, 81 %) showed proliferating capillaries passed over the interlobular septa. Twenty-six cases (26/32, 81 %) showed irregular intimal thickening of small muscular arteries in the peripheral areas of the lesions, with the thickened intima being cellular or fibrous. In twenty-seven cases (27/32, 84 %) the lesions were located in the subpleura, with 6 cases involving the pleura. CONCLUSION: SPCH is a rare benign lung tumor that mostly occurs in the lung lower basal segments with predominance in females. It usually appears as a ground-glass nodule on CT and is very similar to early-stage lung cancer. Accurate diagnosis requires collaboration of radiologists, surgeons, and pathologists. SPCH should be regarded as an important differential diagnosis of small incidental lung nodules.

Characteristics of Metastatic and Nonmetastatic Pulmonary Sclerosing Pneumocytomas: A Clinicopathological Study of 68 Cases and 15 Reported Metastatic Cases.

To characterize the clinicopathologic features of pulmonary sclerosing pneumocytoma (PSP) and compare these features between the tumors with and without metastasis, 68 cases of PSP (1/68 [1.47%] with metastasis) diagnosed from 2009-2022 in our hospital and 15 previously reported metastasizing cases were studied. There were 54 female patients and 14 male patients, with age ranging from 17 to 72 years and tumor size ranging from 0.1 to 5.5 cm (mean, 1.75 cm). In all, 85.4% of the cases presented with ≥2 patterns, including papillary, sclerotic, solid, and hemorrhagic. Thyroid transcription factor 1, epithelial membrane antigen, CKpan, and CK7 were expressed in surface cells in 100% of the cases and napsin A was expressed in 90% of the cases. Stromal cell expression of these markers occurred in 100%, 93.9%, 13.5%, 13.8%, and 0% of the cases, respectively. Of the 16 PSP cases with metastasis, 8 were female patients and 7 were male patients, with age ranging from 14 to 73 years. The tumor size ranged from 2.5 to 12 cm (mean, 4.85 cm). Forty-five of the cases were negative for BRAF V600E immunostaining and 6 were focally weak positive, in which fluorescent PCR tests showed no detectable mutations. There were significant differences in gender, age, and tumor size between PSP cases with and without metastasis. No BRAF V600E mutation was found in patients with PSP. AKT1 p.E17K mutations were detected in both the primary lung tumor and the lymph node metastatic tumor of our PSP case with lymph node metastasis. In conclusion, PSP is an uncommon pulmonary neoplasm with significant female predilection and has distinct morphologic and immunohistochemical characteristics. The BRAFV600E mutation was not detectable in patients with PSP and thus may not involve in its tumorigenesis. Most PSP tumors are benign, with a minority exhibiting potential for metastasis and malignant behavior.

Application of TFE3 Immunophenotypic and TFE3 mRNA Expressions in Diagnosis and Prognostication of Adrenal Cortical Neoplasms and Distinction From Kidney Tumors.

We explored the application of TFE3 immunostaining and TFE3 mRNA expression in the differential diagnosis and prognostication of adrenal cortical tumors and distinction of the latter from clear cell renal cell carcinoma (ccRCC) which show significant morphologic overlap. TFE3 immunostaining was performed on a large cohort of samples including 40 adrenal cortex tissues, 95 adrenocortical adenoma (ACA), 11 adrenocortical carcinoma (ACC), 53 ccRCC, and 18 pheochromocytomas. TFE3 was compared with other immunomarkers melan-A, inhibin-α, synaptophysin, chromogranin A, CAIX and CD10. One hundred percent normal adrenal cortices and 94% ACA were strongly and diffusely stained for TFE3 while no ACC showed diffuse staining. TFE3 is thus useful in distinguishing ACA from ACC. TFE3 is also useful in separating ACC from ccRCC as 64% ACC showed partial, while only 7% of ccRCC showed partial TFE3 staining. Only 1 pheochromocytoma showed focal weak TFE3 staining. Results also demonstrated superiority of TFE3 over other commonly used immunomarkers. TFE3 gene rearrangement testing by fluorescence in situ hybridization showed no rearrangement in 6 TFE3 positive adrenal tumors. TFE3 mRNA were analyzed by the Cancer Genome Atlas database and we found TFE3 mRNA expression correlated with overall patient survival in ACC. Our study showed usefulness of TFE3 in distinguishing ACA from ACC, and ACC from ccRCC. TFE3 is superior over other commonly used immunomarkers for adrenal tumors. In addition, decreased TFE3 immunoexpression and TFE3 mRNA expression may carry poor prognostic implication in adrenal tumors.

Pulmonary artery intimal sarcoma - A primeval or rediscovered tumor? A report of 14 new cases with literature review.

Pulmonary artery sarcomas (PAS) are rare with many being undifferentiated pleomorphic or spindle cell (UPSC) sarcomas with variable atypia. The term pulmonary artery intimal sarcoma (PAIS) was rarely coined in the early literature and sometimes used for luminal sarcomas. With the advent of immunohistochemistry and molecular genetics, many of these UPSC sarcomas were found to frequently overpress MDM2 and/or CDK4 and PDGFRA with genetic alterations in 12q12-15 and 4q12, where the MDM2, CDK4 and PDGFRA genes are located. These recent developments enabled refinement in diagnosis of PAIS. We diagnosed 14 cases of PAIS (6 males and 8 females, mean age 44 years) in 2015 - 2020 in our institution. Six were initially misdiagnosed as thromboembolism and the remaining pulmonary artery tumors. The tumors were pulmonary artery intraluminal polypoid masses with histology of spindle cell sarcomas exhibiting immunohistochemical positivity for MDM2 (100%) and CDK4 (79%) with MDM2 gene amplification (100%). Ten surgically treated patients fared better than four other biopsy only and not surgically treated patients, who died of disease within 5-11 months. PAIS needs to be differentiated from other spindle cell tumors and those exhibiting MDM2 gene amplification, especially dedifferentiated liposarcoma. The use of biopsy to provide diagnostic material poses a sampling error problem and correlation with clinical, radiologic, histologic, immunophenotypic and genotypic features are essential for accurate diagnosis and early surgical intervention of PAIS.

A comparative study of Kimura's disease and IgG4-related disease: similarities, differences and overlapping features.

AIMS: To compare the fibroinflammatory diseases Kimura's disease (KD) and immunoglobulin (Ig)G4-related disease (IgG4RD) and to explore their possible relationship. METHODS AND RESULTS: Forty-six cases of KD and 29 IgG4RD from our institution diagnosed from 2011 to 2020 were studied. They were compared with each other on clinical, pathological and immunohistological features. There were similar clinical features, except that IgG4RD affected an older patient population, with more frequent salivary gland involvement and KD affected head and neck lymph nodes, and showed blood eosinophilia more frequently than IgG4RD. IgG4RD exhibited frequent storiform fibrosis and obliterative phlebitis, while KD showed more frequent tissue eosinophilia, eosinophilic abscess, germinal centre eosinophilic deposit and vascularisation. Twenty to 30% of KD had more than 50 IgG4+ plasma cells (PC) per high-power field (HPF) and IgG4/IgG+ PC ratio exceeding 40%. These parameters, however, occurred in 100% of IgG4RD. Significantly more KD had >10 IgE+ PC/HPF and lymphoid germinal centre IgE reticular staining compared to IgG4RD. All these histological and immunohistological features are overlapping in the two diseases, although they differed with statistical significance. CONCLUSION: Our study confirmed that there is significant overlap in clinical, pathological and immunohistological features between KD and IgG4RD. It is important to recognise these overlapping features, and correlation with a clinicopathological picture is required in differential diagnoses. The overlapping features also suggest a possible close relationship between KD and IgG4RD, which could represent different facets of a continuous fibroinflammatory disease spectrum.

Primary pulmonary myxoid sarcoma with EWSR1-CREB1 fusion: a case report and review of the literature.

BACKGROUND: Primary pulmonary myxoid sarcoma (PPMS) is an extremely rare lung sarcoma that is characterized in most cases by recurrent balanced chromosomal translocation t(2;22)(q33;q12) leading to the oncogenic fusion gene EWSR1-CREB1. CASE PRESENTATION: We report a case of PPMS with molecular confirmation using fluorescence in situ hybridization (FISH) and DNA sequencing in a 45-year-old female patient. Computer tomography (CT) scanning revealed a peripheral circumscribed solid mass of 2.1 × 2 cm in the right lung superior lobe. Histologically, the tumor cells ranged from stellate, polygonal to chondrocyte-like or physaliferous-like, forming reticular network of delicate lace-like cellular strands and cords in abundant myxoid stroma. The tumor cell immunophenotype was positive for vimentin, EMA and negative for CK-pan, TTF-1, CAM5.2, S-100, calponin, SMA, desmin, ALK, CD31 and CD34. Molecular analysis demonstrated EWSR1-CREB1 gene fusion in this tumor. During 38 months of follow-up, the patient was alive with no clinical or radiological evidence of recurrence or metastasis. CONCLUSION: PPMS is a rare low-grade sarcoma with distinct histological and genetic features. We add another case to the literature of this rare tumor and report for the first time occurrence of chondrocyte-like and physaliferous-like tumor cells in this tumor, thus enriching its morphologic and cytologic spectrum.

An unusual case report of indolent T-cell lymphoproliferative disorder with aberrant CD20 expression involving the gastrointestinal tract and bone marrow.

BACKGROUND: Indolent T-cell proliferative disorder of the GIT is a rare and provisional entity in the revised WHO 2016 classification. The patients usually have prolonged survival with persistent disease even without any treatment. CASE PRESENTATION: The 46 years old male patient has been followed up for more than 6 years without chemotherapy. Repeated gastrointestinal biopsies showed expansion of the lamina propria extending to the submucosa by small to medium sized lymphocytes with minimal cytologic atypia. The lymphoid cells were positive for CD3, CD43, TIA-1, CD2, CD7 and the B-cell marker CD20; but negative for CD4, CD8, PAX5, CD56, cyclinD1, granzyme (GraB) and Epstein Barr virus-encoded RNA (EBER). Ki-67(MIB1) index was less than 10%. Molecular tests demonstrated a clonal rearrangement for T-cell receptor γ (TCR γ) gene but immunoglobulin chain (IgH, IgK, IgL) gene remained germline. Recognition of possible aberrant CD20 expression in indolent T-cell LPD is important to avoid potential diagnostic pitfall and improper treatment. CONCLUSIONS: We present an unusual case of indolent T-cell lymphoproliferative disorder with aberrant CD20 expression, Recognition of this unusual immunophenotype of indolent T-cell LPD of GI helps to eschew misdiagnosis of B-cell and other high grade lymphomas and inappropriate aggressive treatment.

Prevalence, Clinicopathological Characteristics, and Outcome of Human Papillomavirus-Associated Oropharyngeal Cancer in Southern Chinese Patients.

BACKGROUND: Although the global incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is increasing, there is little information on southern Chinese population available. METHODS: We analyzed 207 patients which constituted 63.5% of all newly diagnosed OPSCC in Hong Kong during a 5-year period from 2005 to 2009. RESULTS: We used E6/7 mRNA as a marker of oncogenic involvement and found 20.8% (43/207) of OPSCC and 29.0% (36/124) of tonsillar SCC was associated with HPV. HPV-16 was identified in all cases except one (HPV-18). Patients with HPV-associated OPSCCs were significantly younger than HPV-negative patients (mean age: 59.8 vs. 63.9 years, P = 0.05). Multivariate analysis showed that HPV-associated OPSCC was more likely to occur in nonsmokers (39.5% vs. 15.1%, OR: 2.89, P = 0.05), nondrinkers (52.5% vs. 25.6%, OR: 2.72, P = 0.04), originate from the palatine tonsils (83.7% vs. 53.7%, OR: 3.88, P = 0.01), present with an early primary tumor (T1/2; 79.1% vs. 47.6%, OR: 3.81, P = 0.004), and exhibit basaloid differentiation (33.3% vs. 7.3%, OR: 19.74, P = 0.006). HPV positivity was an independent predictor for better prognosis for both 5-year overall and 5-year disease-specific survivals (DSS; 63.0% vs. 29.7%, HR: 0.33, P < 0.001, and 87.8% vs. 42.6%, HR: 0.16, P < 0.001, respectively). CONCLUSION: The estimated age-standardized incidence of OPSCC in Hong Kong during the period 2005-2009 was 0.12/100,000/year. IMPACT: This study has provided the most comprehensive clinical and pathologic information to date about this newly recognized disease in southern Chinese. In view of the global trend, we should anticipate and prepare for an increase in HPV-related OPSCC in southern China.