Pulmonary adenocarcinoma with micropapillary pattern: a clinicopathologic and immunohistochemical study / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic characteristics and immunohistochemical profile of lung adenocarcinomas with a micropapillary pattern (MPP).</p><p><b>METHODS</b>Among 135 cases of lung adenocarcinomas, the clinical, histological and immunohistochemical features of 48 cases of lung adenocarcinomas with a micropapillary components (the micropapillary components > or = 10%) were studied. The literature was reviewed.</p><p><b>RESULTS</b>All the 135 cases were resected pulmonary adenocarcinomas. Among 48 cases of lung adenocarcinomas with a micropapillary components, the age of patients ranged from 43 to 85 years (mean = 60.7 years). The male-to-female ratio was 9:7. Histologically, 36 cases of lung adenocarcinomas with the MPP were characterized by small papillary tufts lacking a central fibrovascular core lying freely within alveolar spaces (IA type) or in the clefts of fibrous tissue just like those in MPP breast cancers (IB type). Another type of the micropapillary pattern consisted of 12 cases, the micropapillary tufts floating within cystic spaces lined by tumor cells (II type). In micropapillary pattern-positive cases, lymphatic invasion and lymph node metastasis were identified significantly more frequently than in micropapillary pattern-negative cases (P < 0.01). The percentages of cases positive for various markers were 97.9% (47/48) for E-cadherin, 89.5% (43/48) for beta-catenin, 91.7% (44/48) for Muc-1, 70.8% (34/48) for epidermal growth factor receptor, 35.4% (17/48) for p53, 93.8% (45/48) for Ki-67. The percentages of cases with high expression (including 3+ or 4+) for these markers were 72.3% (34/47) for E-cadherin, 90.7% (39/43) for beta-catenin, 88.6% (39/44) for Muc-1, 52.8% (19/36) for epidermal growth factor receptor, 58.8% (10/17) for p53, 46.7% (16/36) for Ki-67. Adequate clinical follow-up information was available for 36 patients. The mean follow-up time was 21.1 months. Among these, 16 of 36 patients (44.4%) were alive with no evidence of tumor, 12(33.3%) were died, and 8 (22.2%) were alive with tumor.</p><p><b>CONCLUSION</b>Lung adenocarcinomas with the MPP correlates positively with lymphatic invasion and lymph node metastasis, and are likely to have a potential for high malignancy, suggesting a poor prognosis.</p>

Clinicopathologic study of primary marginal zone B-cell lymphoma of MALT type and lymphoid hyperplasia of lung / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunohistochemical findings and immunoglobulin heavy chain (IgH) gene rearrangement results of primary pulmonary mucosa-associated lymphoid tissue lymphoma (MALToma) and reactive lymphoid hyperplasia.</p><p><b>METHODS</b>Twenty cases, included 13 cases of pulmonary MALToma and 7 cases of pulmonary lymphoid hyperplasia, encountered during the period from 1989 to 2007, were retrospectively analyzed. The samples were paraffin-embedded and stained with hematoxylin and eosin. Immunohistochemical study and semi-nested polymerase chain reaction for IgH gene rearrangement were performed.</p><p><b>RESULTS</b>The 13 cases of primary pulmonary MALToma were composed of a spectrum of lymphoid cells, including lymphocyte-like cells, centrocyte-like cells and mononuclear B cells with plasmacytoid differentiation. They often had diffuse or marginal zone growth patterns. Lymphoid follicles with neoplastic colonization were apparent. The lymphoma cells spread along alveolar septa and bronchovascular bundles. Vascular invasion was noted in 9 cases, pleura involvement in 6 cases and nodal involvement in 2 cases. Lymphoepithelial lesions (LEL) were identified in 9 cases of pulmonary MALToma. Immunohistochemically, the lymphocytes in LEL were CD20-positive and CD3-negative. On the other hand, LEL was also present in 2 of the 7 cases of lymphoid hyperplasia studied, with a mixture of CD20-positive B cells and CD3-negative T cells. Eight of the 9 cases of primary pulmonary MALToma were positive for IgH gene rearrangement, while all of the 7 cases of lymphoid hyperplasia were negative.</p><p><b>CONCLUSIONS</b>Histologically, the cell population of primary pulmonary MALToma is similar to that of extranodal MALToma occurring in other organs. LEL, though commonly observed in pulmonary MALToma, are not specific and can also be seen in cases of reactive lymphoid hyperplasia. The immunophenotype of intraepithelial lymphocytes in pulmonary MALToma and reactive lymphoid hyperplasia is different. The presence of a monotonous population of CD20-positive intraepithelial lymphocytes supports a diagnosis of MALToma. IgH gene rearrangement study is also useful in differentiating both entities.</p>

Intraductal papillary mucinous neoplasm of pancreas: a clinicopathologic and immunohistochemical study of 19 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features and diagnosis of intraductal papillary mucinous neoplasm (IPMN) of the pancreas.</p><p><b>METHODS</b>Nineteen cases of IPMN encountered during the period from 1999 to 2007 were studied by light microscopy and immunohistochemistry.</p><p><b>RESULTS</b>IPMN occurred more often in males (68%). It affected patients in older age group (mean age = 59) and was located mainly in the head of pancreas (60%). The mean tumor size was 4.2 cm (range = 1 to 8 cm). The clinical presentation was epigastric pain (53%), weight loss (32%), diabetes (21%), pancreatitis (21%) and jaundice (10%). Pancreatectomy was performed in 18 cases. The remaining patient received bypass surgery only. Features of in-situ or invasive malignancy were present in 15 of the 19 cases (78%). Histologically, the tumor consisted of papillary proliferations protruding into and expanding the pancreatic ducts. Invasion into the surrounding pancreatic parenchyma was noted in 12 cases and chronic pancreatitis was present in 16 cases. Follow-up data (4 to 48 months) were available in 13 patients. Apart from 1 patient who died of other disease, all were still alive. Immunohistochemical study showed that p53 was positive in 6 cases, p16 in 5 cases and fascin in 8 cases. The expression of c-erbB-2 was all negative. Ki-67 index ranged from 1% to 80% (mean = 38%).</p><p><b>CONCLUSIONS</b>Malignant changes are not uncommon in IPMN. The prognosis after surgical resection however is better than that of conventional pancreatic adenocarcinoma. The overexpression of p53, p16 and fascin may be related to tumor progression. The possibility of malignant transformation needs to be considered if the Ki-67 index is over 15%. Early recognition by radiologic examination (including ERCP) and pancreatic cytology would be helpful in early diagnosis. Surgical resection represents the mainstay of treatment and long-term post-operative follow up is needed.</p>

Role of HPV DNA detection and p16(INK4A) protein expression in diagnosis of endocervical adenocarcinoma / 中华病理学杂志

<p><b>OBJECTIVES</b>To evaluate the significance of p16(INK4A) protein expression and positivity for HPV DNA in distinguishing between endocervical and endometrial adenocarcinoma.</p><p><b>METHODS</b>Expression of p16(INK4A) protein in 30 cases of endocervical adenocarcinoma and 10 cases of endometrial adenocarcinoma was assessed by immunohistochemistry. In-situ hybridization for human papillomavirus (HPV) DNA was also performed in 20 cases of endocervical adenocarcinoma and 10 cases of endometrial adenocarcinoma.</p><p><b>RESULTS</b>The positive rate for p16(INK4A) in endocervical adenocarcinoma was 70% (21/30), as compared with 30% (3/10) in endometrial adenocarcinoma. The tumor cells in endocervical adenocarcinoma showed diffuse and strong expression of p16(INK4A) protein with both cytoplasmic and nuclear staining. In contrast, the endometrial adenocarcinoma cells showed patchy and weak expression of p16(INK4A). On the other hand, HPV DNA (type 16 or 18) was detected by in-situ hybridization in 9 (45%) of the 20 cases of endocervical adenocarcinoma and none of the 10 cases of endometrial adenocarcinoma.</p><p><b>CONCLUSIONS</b>The expression of p16(INK4A) protein is significantly higher in endocervical adenocarcinoma than in endometrial adenocarcinoma. This expression pattern can serve as a useful immunohistochemical marker in the differential diagnosis. p16(INK4A) protein immunohistochemistry appears to be more sensitive than HPV DNA testing in distinguishing between endocervical and endometrial adenocarcinoma, especially in biopsy or curettage specimens.</p>

Atypical adenomatous hyperplasia of lung: clinicopathologic study of 8 cases and review of literature / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic and immunohistochemical features of atypical adenomatous hyperplasia (AAH) of lung.</p><p><b>METHODS</b>Eight cases of AAH of lung were studied by light microscopy and immunohistochemical staining for p16, thyroid transcription factor-1 (TTF-1), Ki-67, p53, epidermal growth factor receptor (EGFR) and c-erbB-2.</p><p><b>RESULTS</b>The mean age of the patients was 52 years. The male-to-female ratio was 1:3. Two patients were chronic smokers. The clinical symptoms were relatively non-specific. Three patients had past history of non-pulmonary tumors, while 4 patients had lung adenocarcinoma. CT scan revealed solitary or multifocal hyperdense opacities. Histologically, the lesions ranged from 1 mm to 6 mm in size. Two cases were solitary and 6 cases were multifocal. All were of high-grade lesions. Associated low-grade component was noted in 3 cases. There was no evidence of local recurrence or disease progression in the 7 patients with post-operative follow-up information available (mean duration of follow up = 23 months). Four patients had received chemotherapy as well. Immunohistochemical study showed variable positivity for p16 (5/8), TTF-1 (5/8), Ki-67 (with proliferation index ranging from 1% to 10%), p53 (1/8) and EGFR (1/8). The staining for c-erbB-2 was negative (0/8). Four cases of AAH were associated with pulmonary adenocarcinoma. The adenocarcinoma cells were diffusely positive for TTF-1 (4/4), variably positive for p16 (2/4), Ki-67 (with proliferation index ranging from 2% to 40%), p53 (1/4) and EGFR (3/4), and negative for c-erbB-2 (0/4).</p><p><b>CONCLUSIONS</b>AAH of lung is associated with pulmonary adenocarcinoma. Diagnosis of AAH requires correlation with CT findings and pathologic examination.</p>

Distinction between benign and malignant pheochromocytomas / 中华病理学杂志

<p><b>OBJECTIVES</b>To investigate the differences in morphology, immunohistochemistry, DNA ploidy status, LOH and MSI of 11q13 and 1p between benign and malignant pheochromocytomas, and to find the marker or markers useful in distinction between benign and malignant pheochromocytoma or for predicting the malignant potential of this tumor.</p><p><b>METHODS</b>Twenty-two cases of clinically documented benign and malignant pheochromocytomas from the files of Peking Union Medical College Hospital were analyzed. Aside from histological study, Ki-67, p53, CgA, S-100, PCNA and survivin immunohistochemistry studies were performed. DNA ploidy status was assessed by flow cytometry on cell suspensions prepared from formalin-fixed, paraffin-embedded sections. Twelve tumors (7 benign and 5 malignant) with paired normal tissues were microdissected. Tumor and normal tissue DNA were extracted. The obtained DNAs and 8 microsatellite markers related to 11q13 and 1q were subjected to PCR amplification for analysis of LOH and MSI.</p><p><b>RESULTS</b>None of the tumors showed atypical mitosis, only 1 malignant tumor had a mitotic count > 1/10 HPF (2.3/10 HPF). Two malignant tumors exhibited confluent necrosis. Ki-67 index was low in benign tumors (average 0.73%), and high in malignant tumors (average 2.4%). The difference of Ki-67 index between benign and malignant tumors was statistically significant. DNA ploidy status did not correlate with malignancy. Although LOH and/or MSI of 11q13 and 1p were observed in several tumors, a statistically significant difference could not be reached due to the small number of tumors analyzed.</p><p><b>CONCLUSION</b>Only Ki-67 index (> 3%) is an useful marker for distinguishing benign from malignant or for predicting the malignant potential of pheochromocytoma.</p>

Lung pathology of severe acute respiratory syndrome / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the morphological features of the lungs obtained from autopsies of severe acute respiratory syndrome (SARS) patients.</p><p><b>METHODS</b>Bilateral lungs from 7 patients died from SARS were carefully studied grossly and microscopically. All tissues from these cases were routinely processed and carefully studied.</p><p><b>RESULTS</b>All lungs from these cases were extremely expanded and became solid. Microscopically, the edema and fibrin exudates in the alveoli was the most common findings, especially in the early phase of the disease. The hyaline membrane was almost always present in the lungs of these cases. The organization of intra-alveolar fibrin exudates along with the interstitial fibrosis led to obliteration of alveoli and consolidation of lungs. The desquamation and hyperplasia of alveolar lining cells was also apparent. Foci of haemorrhage and lobular pneumonia, even diffuse fungal infection were frequently seen in these specimens. Micro-thrombus were easily found in these lungs.</p><p><b>CONCLUSIONS</b>The lung of SARS from autopsy is characterized by edema, intra-alveolar fibrin exudates, hyaline membrane formation, organization of intra-alveolar exudates and fibrosis, which lead to the obliteration of alveoli and consolidation of lungs.</p>

Immunohistochemical investigation of lungs with severe acute respiratory syndrome / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the roles of different cells in the pulmonary lesions in the severe acute respiratory syndrome (SARS) patients.</p><p><b>METHODS</b>The monoclonal antibodies of CD8, CD20, CD34, LCA, CD56, CD68, and AE1/AE3 are used to demonstrate the different cells in the lung specimens of SARS patients in order to study the patterns of cell responses in this new disease. Meanwhile the HE stained slides were also carefully studied to compare with the results of immunohistochemical staining.</p><p><b>RESULTS</b>The number of capillaries increased and the capillaries clearly outlined the contour of alveolar wall from beginning to early stage of organization, the number of lymphocytes decreased sharply while the number of macrophage remarkably increased, together with proliferation of type II pneumocytes. The numbers of blood vessels decreased in the fibrotic and consolidated lung tissue, and the vessel cavities enlarged, losing the normal contour of alveolar septa.</p><p><b>CONCLUSIONS</b>The lesions in the lung from SARS patients are consisted of the tissue reaction to the inflammatory injury, including extensive exudation, capillary proliferation, fibrosis, and obvious infiltration of macrophages which may play a key role in the pathogenesis of pulmonary lesions of SARS.</p>

Morphological study of severe acute respiratory syndrome (SARS) / 中华病理学杂志

<p><b>OBJECTIVE</b>Seven cases of autopsy from SARS patients are studied to investigate the pathogenesis and the pathologic changes of the major organs.</p><p><b>METHODS</b>Detailed gross and microscopic examination of the autopsy specimen is performed, including lung, heart, liver, kidney, spleen and lymph nodes.</p><p><b>RESULTS</b>All of the lungs are markedly enlarged and consolidated. Microscopically, pulmonary edema is a prominent finding, especially at the early stage of the disease (5 days after the onset). The alveolar spaces are filled with fibrinous exudates and lined with hyaline membrane. In 5 cases that undergo over 3 weeks of the course, the main pattern is organization of intra-alveolar deposit, along with fibroblastic proliferation in the alveolar septa, which leads to obliteration of alveolar space and pulmonary fibrosis. All of the lungs show bronchopneumonia, scattered hemorrhage, and proliferation of alveolar epithelial cells with desquamation. Microthrombi are seen in 6 cases. Fungal infection is noted in 2 cases. One of them is disseminative, involving bilateral lungs, heart, and kidney; the other one is diagnosed in hilar lymph nodes. In immune system, hilar and abdominal lymph nodes are usually congested and hemorrhagic, with depletion of lymphocytes, and accompanied with subcapsular sinus histiocytosis. One of the cases shows enlargement of abdominal lymph nodes, which have reduced number of germinal centers. Spleen exhibits atrophy of white pulps, and even lost of white pulps in some areas. The red pulp is markedly congested and hemorrhagic. In 5 cases, cardiomegale is prominent. Thrombosis (2 cases), focal myocarditis (1 case), and fungal myocarditis (1 case) are observed. In addition, liver shows massive necrosis (1 case) and nodular cirrhosis (1 case).</p><p><b>CONCLUSIONS</b>Lung is the major organ affected by SARS, demonstrated as diffuse alveolar damage. It is postulated that viral infection induces severe damage of alveolar epithelial and capillary endothelial cells, leads to pulmonary edema, intra-alveolar fibrin deposit, and hyaline membrane formation. Consequently, intra-alveolar organization and alveolar septal fibrosis causes loss of alveolar spaces, eventually, pulmonary fibrosis and atelectasis. The immune system is often affected, and presented as depletion of lymphoid tissue in lymph nodes and spleen. Secondary infection is a common complication, which should be paid close attention in the management of SARS patients.</p>