Prognostic significance of locally invaded sites and tissue types in patients with nasal extranodal natural-killer/T-cell lymphoma: a single-center retrospective analysis / 中华医学杂志(英文版)

Background@#Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, is an aggressive entity within the World Health Organization classification of lymphoid tumors. The International Prognostic Index is reported to be prognostically meaningful for ENKTL, but lacks discriminatory power for stage I/II ENKTL with extensive local invasion. This study aimed to evaluate the prognostic effects of local invasion by site and tissue type in patients with ENKTL.@*Methods@#We retrospectively analyzed data of 86 patients who were diagnosed with ENKTL by the Department of Pathology of Beijing Tongren Hospital from June 2002 to April 2016, and ascertained tumor infiltration of adjacent structures (AS), bone, and soft tissue for each patient, using physical findings and imaging scans. We used univariate and multivariate analysis to assess the association of each involved tissue or site with patients’ overall survival (OS).@*Results@#Of the 86 patients, 71(82.6%) experienced invasion of AS, 22(25.6%) of soft tissue, and 26(30.2%) had bone involvement. Overall, patients with AS involvement did not show significantly shorter survival than those without AS involvement (Log rank χ2 = 1.177, P = 0.278); however, patients who had involved eyeballs or brains showed significantly lower 2-year OS rates than those without eyeball involvement (Log rank χ2 = 4.105, P = 0.043) or brain involvement (Log rank χ2 = 7.126, P = 0.008). Patients with involved local soft tissue or bones, respectively, showed lower 2-year OS rates than those without involved local soft tissue (Log rank χ2 = 10.390, P = 0.001) or bones (Log rank χ2 = 8.993, P = 0.003). Multivariate analysis showed that involvement of the cheek or facial muscles (hazard ratio, HR = 5.471, 95% confidence interval [CI]: 1.466–20.416, P = 0.011) and the maxilla bone (HR = 6.120, 95% CI: 1.517–24.694, P = 0.011) were significantly independent predictors of lower 2-year OS rates.@*Conclusions@#Imaging can accurately detect ENKTL invasion of AS, soft tissue, and bone. Involvement of local soft tissue or bone was significantly associated with lower 2-year OS rates. Involvements of the cheek or facial muscle, as well as maxilla bone, are independent predictors of lower 2-year OS rates in ENKTL patients.

Prognostic significance of locally invaded sites and tissue types in patients with nasal extranodal natural-killer/T-cell lymphoma: a single-center retrospective analysis / 中华医学杂志(英文版)

BACKGROUND@#Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, is an aggressive entity within the World Health Organization classification of lymphoid tumors. The International Prognostic Index is reported to be prognostically meaningful for ENKTL, but lacks discriminatory power for stage I/II ENKTL with extensive local invasion. This study aimed to evaluate the prognostic effects of local invasion by site and tissue type in patients with ENKTL.@*METHODS@#We retrospectively analyzed data of 86 patients who were diagnosed with ENKTL by the Department of Pathology of Beijing Tongren Hospital from June 2002 to April 2016, and ascertained tumor infiltration of adjacent structures (AS), bone, and soft tissue for each patient, using physical findings and imaging scans. We used univariate and multivariate analysis to assess the association of each involved tissue or site with patients' overall survival (OS).@*RESULTS@#Of the 86 patients, 71 (82.6%) experienced invasion of AS, 22 (25.6%) of soft tissue, and 26 (30.2%) had bone involvement. Overall, patients with AS involvement did not show significantly shorter survival than those without AS involvement (Log rank χ = 1.177, P = 0.278); however, patients who had involved eyeballs or brains showed significantly lower 2-year OS rates than those without eyeball involvement (Log rank χ = 4.105, P = 0.043) or brain involvement (Log rank χ = 7.126, P = 0.008). Patients with involved local soft tissue or bones, respectively, showed lower 2-year OS rates than those without involved local soft tissue (Log rank χ = 10.390, P = 0.001) or bones (Log rank χ = 8.993, P = 0.003). Multivariate analysis showed that involvement of the cheek or facial muscles (hazard ratio, HR = 5.471, 95% confidence interval [CI]: 1.466-20.416, P = 0.011) and the maxilla bone (HR = 6.120, 95% CI: 1.517-24.694, P = 0.011) were significantly independent predictors of lower 2-year OS rates.@*CONCLUSIONS@#Imaging can accurately detect ENKTL invasion of AS, soft tissue, and bone. Involvement of local soft tissue or bone was significantly associated with lower 2-year OS rates. Involvements of the cheek or facial muscle, as well as maxilla bone, are independent predictors of lower 2-year OS rates in ENKTL patients.

Sinonasal mammary analogue secretory carcinoma: a clinicopathological analysis of 2 cases / 临床与实验病理学杂志

Purpose To investigate the clinicopathological features of sinonasal primary secretory carcinoma (SC) and its diagnosis, differential diagnosis. Methods Two cases of sin-nasal SC were analyzed by light microscopy with immunohisto-chemical staining (EnVision) for CK, vimentin, S-100 protein, SOX10, PAS, DPAS, Mamaglobin, Calponin, DOG1, p63 and molecular detection of ETV6 gene break. Results Morphologically, SC revealed varying proportions of solid, tubular, acinar, microcystic, tubular growth patterns. All SC cases were cytological low grade with uniform cells, small-to medium-sizes nuclei, occasional small nucleoli, and abundant pink, bubbly cytoplasm. Mitotic figures were rarely encountered. Tumor cells secreted eosinophilic, colloid-like secretions that were PAS positive. There were no DPAS positive zymogen granules in cyto-plasm. This tumor cells were CK, vimentin, S-100, SOX10, PAS positive and Mamaglobin, Calponin and p63 negative. The ETV6 gene rearrangement was confirmed in all cases by fluorescence in situ hybridization (FISH). After excision, all two patients were survival without tumor recurrence for 41 months and53 months. Conclusion Sinonasal primary SC is a low grade malignant tumor. The histological features of SC are overlap with other salivary gland tumors. Immunohistochemical analysis and FISH are useful for the diagnosis and differential diagnosis.

Expression and significance of IgG4 in inflammatory disease of nasal cavity and paranasal sinuses / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the prevalence of IgG4-positive plasma cells in inflammatory disease of nasal cavity and paranasal sinuses and its association with IgG4-related sclerosing disease (IgG4-SD).</p><p><b>METHODS</b>The expression of IgG4 and IgG in plasma cells of 103 cases diagnosed as inflammatory disease of nasal cavity and paranasal sinuses with dense lymphoplasmacytic infiltrate was studied by immunohistochemistry (EnVision) and quantitatively analyzed by medical image analysis system.</p><p><b>RESULTS</b>Immunohistochemical study showed marked infiltration by IgG4-positive plasma cells (>50 per high-power field) in 28 cases, moderate infiltration (30 to 50 per high-power field) in 23 cases, mild (10 to 29 per high-power field) in 30 cases and negative (<10 per high-power field) in 22 cases (P < 0.05). Twenty-two cases studied fulfilled the diagnostic criteria of IgG4-SD (>50 IgG4-positive plasma cells per high-power field and IgG4-to-IgG ratio > 40%), including 3 cases of chronic sinusitis (3/20), 3 cases of nasal polyps (3/18), 3 cases of inflammatory pseudotumor (3/17), 4 cases of fungal sinusitis (4/20), 1 case of rhinoscleroma (1/12), 7 cases of Wegener's granulomatosis (7/11) and 1 case of Rosai-Dorfman disease (1/2).</p><p><b>CONCLUSION</b>Inflammatory disease of nasal cavity and paranasal sinuses fulfilling the diagnostic criteria IgG4-SD is not uncommon. Definitive diagnosis of IgG4-SD requires correlation with other clinical and laboratory findings. Some cases of unexplained inflammatory disease of nasal cavity and paranasal sinus may represent a member of the IgG4-SD spectrum. IgG4 carries diagnostic value in differential diagnosis of inflammatory disease occurring in nasal cavity and paranasal sinuses.</p>

High-grade transformation in adenoid cystic carcinoma: a clinicopathologic study / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features and possible molecular mechanisms of adenoid cystic carcinoma with high-grade transformation.</p><p><b>METHODS</b>Four cases of adenoid cystic carcinoma with high-grade transformation were enrolled into the study. Immunohistochemical study for smooth muscle actin, p63, p53 and Ki-67 was carried out. C-myc gene status was analyzed by fluorescence in-situ hybridization.</p><p><b>RESULTS</b>There were altogether 3 males and 1 female. The mean age of the patients was 55.5 years. Two patients died 17 months and 29 months after operation, respectively. One patient had distant metastasis 23 months after operation and was still alive at 26-month follow up. The remaining patient remained tumor free at 3-month follow up. High-grade transformation in adenoid cystic carcinoma presented either as poorly differentiated adenocarcinoma or undifferentiated carcinoma. Histologic examination showed sheets of pleomorphic tumor cells occupying more than one low-power field. The high-grade carcinoma cells showed increased nuclear-cytoplasmic ratio, prominent eosinophilic nucleoli and active mitosis (ranging from 8 to 25 per high-power field). Comedo necrosis was observed in 2 cases and multiple foci of calcifications in 3 cases. Immunohistochemical study demonstrated loss of myoepithelial differentiation, overexpression of p53 and high proliferative index by Ki-67. No c-myc translocation or copy-number changes were observed.</p><p><b>CONCLUSIONS</b>High-grade transformation in adenoid cystic carcinoma is rare. The histopathologic features are rather distinctive and the biologic behavior is aggressive. C-myc gene mutation does not seem to play a key role in the pathogenesis.</p>

Application of PCR combined with reverse line blot assay in detection and identification of common pathogenic Aspergillus in fungal sinusitis / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the feasibility of PCR/reverse line blot hybridization (RLB) assay in the detection and identification of clinical pathogens in fungal sinusitis (FS).</p><p><b>METHODS</b>Twenty-six formalin-fixed and paraffin-embedded tissues and 8 fresh tissues of FS were collected from Beijing Tongren Hospital, Capital Medical University from May 2009 to February 2010. Pathological examination, fungal culture and ITS2 region sequencing were carried out. The DNA of all samples was extracted by standard procedure and fungal universal primers ITS3 and ITS4 were used for PCR amplification of all tissues. Then the amplified products were used for RLB with five fungal species-specific probes. The results of PCR/RLB were compared with ITS region sequencing, fungal culture and pathological examination.</p><p><b>RESULTS</b>For the biopsy tissues, fungal cultures were positive in 14 cases (41.2%); pathologic examination demonstrated fungal hyphae in all cases; ITS2 region sequencing was successful in 16 cases (47.1%); PCR/RLB showed A. flavus in 14 cases, A. fumigatus in 10 cases, A. niger in four cases, A. nidulans in one case, A. flavus and A. fumigatus in three cases, and A. fumigatus and A. niger in two cases.</p><p><b>CONCLUSIONS</b>The PCR/RLB assay is suitable for rapid and accurate detection and identification of the pathogenic fungus of FS. Compared with the conventional fungal culture and microscopy, pathologic examination and DNA sequencing, the PCR/RLB has the advantages of more economy, time saving, and higher sensitivity, specificity and throughput.</p>

Effects of mast cells on degradation of collagen fibers in dimethylnitrosamine-induced hepatic fibrosis of rat / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between mast cell and hepatic fibrosis by histopathological method and semi-quantitative measurement.</p><p><b>METHODS</b>Seventy-two Wistary male rats, the control group and the normal group of each only 16, experimental group of 40 rat liver fibrosis was induced by injection of DMN and was sampled at eight different time points. HE, histochemistry, immunohistochemistry (ABC method) and immunofluorescence were performed. The size of fibrosis and the number of mast cells were counted. The expression of MMP-2 and TIMP-2 was documented and electron microscopic examination was performed.</p><p><b>RESULTS</b>After injection of DMN, the fibrosis was the most severe in the 2 week (3.72%) and the first month (3.73%, P = 0.2626), and then gradually diminished, although residual fibrosis was still present at 12 months (1.42%, P = 0.0003). The appearance of mast cells began at 2 weeks (1.73 per 200 power field in average by light microscope) after the injection and reached the peak at 4 months (3.06, P = 0.008). Residual amount of mast cells were present at 12 months (1.04, P = 0.045). However, the degree of fibrosis was not proportional or overlapping with the number of mast cells in this experiment model. Mast cells expressed MMP-2 but not TIMP-2.</p><p><b>CONCLUSIONS</b>In the DMN-induced rat liver fibrosis model, mast cell may be an integral player in the pathogenesis of liver fibrosis and may contribute to the degradation of fibrosis by synthesizing and secreting MMP-2.</p>

Utility of NUT gene expression and rearrangement in diagnosis of NUT midline carcinoma in upper respiratory tract / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the importance of expression of the NUT gene and its rearrangement in diagnosing NUT midline carcinoma (NMC) of the upper respiratory tract; and to evaluate the prevalence, histological features and differential diagnosis of NMC of the upper respiratory tract.</p><p><b>METHODS</b>One-hundred and sixty-three small cell malignant tumors of the upper respiratory tract were reviewed at the Beijing Tongren Hospital, Capital Medical University over a 20-year period. These cases included poorly-differentiated squamous cell carcinomas (n = 31), undifferentiated carcinoma (n = 1), non-keratizing undifferentiated nasopharyneal carcinomas (n = 60), small cell neuroendocrine carcinomas (n = 6) and non-epithelial small round cell malignant tumors (n = 65). The clinical and pathologic features were investigated. All cases were subjected to Epstein-Barr virus encoded RNA (EBER) in situ hybridization and NUT monoclonal antibody immunohistochemical staining. Cases positive for NUT immunohistochemistry and negative for EBER in situ hybridization were submitted for fluorescent in situ hybridization (FISH) for rearrangements in both BRD4 and NUT genes, and immunohistochemical staining for a set of cytokeratins (AE1/AE3, CK7, CK8), p63,and neuroendocrine markers (NSE, Syn, CgA, S-100 protein, CD56).</p><p><b>RESULTS</b>Three cases of poorly-differentiated squamous cell carcinomas and one case of undifferentiated carcinoma showed diffuse nuclear immunohistochemical staining with antibody against NUT. These positive cases approximately accounted for 12.5% (4/32) of this group, 4.1% (4/98) of the malignant epithelial carcinomas and 2.5% (4/163) of all small round cell malignant tumors in the study. The age of these patients were 42 - 59 years. Other groups were all negative for NUT immunohistochemistry. These four cases also stained for antibodies against cytokeratins and p63, but were negative for neuroendocrine markers and not associated with EBV infection. Only two of these four cases showed rearrangements of the NUT and BRD4 genes by FISH. These two patients died within one year. The other two patients that did not demonstrate NUT rearrangement by FISH were alive and did not have an aggressive clinical course, surviving 40 and 12 months respectively.</p><p><b>CONCLUSIONS</b>NMC is a rare small round cell malignant tumor in the upper respiratory tract. Only in the groups of primary poorly differentiated squamous cell carcinoma and undifferentiated carcinoma were positive for NUT immunohistochemical staining and NUT rearrangement by FISH. NMC typically occurs in midline organs, and affects the sinonasal tract. It is not associated with EBV infection. There is difference in the clinical course and prognosis among NMC patients. NUT immunohistochemical staining and NUT gene rearrangement analysis can differentiate NMC from other small cell tumors in the upper respiratory tract.</p>

Clinicopathologic study of invasive fungal rhinosinusitis caused by Aspergillus and Mucorales / 中华病理学杂志

<p><b>OBJECTIVE</b>To compare the differences in clinicopathologic features of invasive fungal rhinosinusitis caused by Aspergillus and Mucorales, and to discuss the pathogenesis of tissue injury induced by these two kinds of fungi.</p><p><b>METHODS</b>The clinical and pathologic features of 19 patients with invasive fungal rhinosinusitis due to Aspergillus (group A) and 16 patients with invasive fungal rhinosinusitis due to Mucorales (group M) were retrospectively reviewed. HE, PAS and GMS stains were performed on all the paraffin-embedded tissues. The diagnosis was confirmed by histologic examination and microbiological culture results.</p><p><b>RESULTS</b>Amongst the group A patients, the clinical course was acute in 4 cases and chronic in 15 cases. Thirteen cases had underlying predisposing conditions, including diabetes (number = 4), malignant tumor (number = 5), history of trauma (number = 1) and radical maxillary sinus surgery (number = 3). Follow-up information was available in 13 patients. Seven of them died, 4 due to fungal encephalopathy and 3 due to underlying diseases. Amongst the group M patients, the clinical course was acute in 14 cases and chronic in 2 cases. Fourteen cases had underlying predisposing conditions, including diabetes (number = 8), malignant tumor (number = 5) and history of wisdom tooth extraction (number = 1). Follow-up information was available in 14 patients. Four of them died of fungal encephalopathy. There was significant difference in clinical onset between the two groups (P = 0.01). There was however no difference in terms of underlying predisposing conditions and disease mortality. Histologically, the microorganisms in group A patients formed fungal masses and attached to the mucosal surface, resulting in necrotic bands (11/19). Epithelioid granulomas were conspicuous but multinucleated giant cells were relatively rare. Deep-seated necrosis, granulomatous inflammation against fungal organisms (3/19) and vasculitis with thrombosis (4/19) were not common. On the other hand, large areas of geographic necrosis involving deep-seated tissue could be seen in group M patients (13/16). Isolated multinucleated giant cells were commonly seen. Granulomatous inflammation against fungal organisms were identified (16/16). Vasculitis and thrombosis were also observed (10/16).</p><p><b>CONCLUSIONS</b>The invasiveness of Mucorales is remarkable; and when it causes invasive fungal rhinosinusitis, the clinical course is often acute and large areas of tissue necrosis can be seen. The invasiveness of Aspergillus in tissue is relatively mild. Granulomas are more common and the disease often runs a chronic clinical course. There is however no significant difference in long-term mortality. The pathogenesis may be related to the different components of the fungi.</p>

Patterns and incidence of sinonasal malignancy with orbital invasion / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Sinonasal malignancy with orbital invasion is rare. The objective of the current study was to evaluate the clinical and pathological features, treatment outcomes and survival rates for these malignancies.</p><p><b>METHODS</b>Ninety-three patients who were treated between 1997 and 2007 were retrospectively reviewed. Age, life style, symptoms, location of lesions, previous occurrences, histological subtypes, and treatment modalities were analyzed.</p><p><b>RESULTS</b>Ninety-three patients were evaluated, including 51 men and 42 women: the gender ratio was 1.2 men to 1.0 women. The median age was 40.5 years old. The nasal cavity (34.4%), the maxillary sinus (29.0%) and the ethmoid sinus (19.4%) were the most common primary malignant tumor sites. Almost half of the patients, 44.1% had squamous cell carcinoma, 13.9% had neuroectodermal carcinoma, 11.7% had rhabdomyosarcoma, 9% had adenocarcinoma and salivary gland-type carcinoma, and 11% had other malignancy. The majority of patients presented with T3/T4 (99%), N0 (93.1%), M0 (98%) disease. The distant metastasis rate was 20.9%. The overall survival and disease-free survival rates were 68.1% and 40.9% at three years, respectively. When the overall survival rate was computed according to the epicenter of the original malignant tumor, patients with nasal cavity malignancy and maxillary sinus had the best survival, and patients with ethmoid sinus malignancy had the worse survival (P = 0.03). According to their pathology classification, patients with rhabdomyosarcoma had worse overall survival than those with squamous cell carcinoma, or neuroendocrine carcinoma (P < 0.001). Squamous cell carcinoma and rhabdomyosarcoma invaded the orbit more often and malignancy of the nasal cavity invaded the orbit more than malignancy of the nasal sinus.</p><p><b>CONCLUSIONS</b>For nasal orbital tumors early diagnosis is crucial. Orbital exenteration and postoperative rehabilitation should be carefully considered. The current data suggest that surgical resection with postoperative radiation therapy may offer durable local control.</p>

Analysis of component and source of fine particulate matter in sarcoidosis granulomatous cells / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the source of the fine particulate matter (PM(2.5)) in the sarcoidosis granulomatous cell and the relationship between the sarcoidosis and the PM(2.5) in the atmosphere.</p><p><b>METHODS</b>Paraffin-embedded tissues of 50 cases of human sarcoidosis biopsy samples, 10 cases of non-sarcoidosis autopsy lung samples, 18 cases of lung tissues (with granulomatous lesions) of rats exposed to PM(2.5) by bronchial infusion, and the free PM(2.5) sample in the atmosphere were collected. The characteristics of tissues above mentioned were observed under the light microscopy, which stained by HE staining and Warthin-Starry silver staining. The characteristics of the PM(2.5) in the four groups were analyzed using confocal Raman microscopy. The component of the PM(2.5) in the sarcoidosis granuloma was analyzed using transmission electron microscope-energy dispersive X-ray detector (TEM-EDX), and the component of the PM(2.5) in the atmosphere was analyzed with X-ray fluorescence separately.</p><p><b>RESULTS</b>The PM(2.5) in the four groups have the similar Raman spectrum, they share the feature of carbonaceous composition, the element component of PM(2.5) in the human sarcoidosis was the same as PM(2.5) in the atmosphere.</p><p><b>CONCLUSION</b>The study provided the further evidence that the PM(2.5) in the sarcoidosis lesion was from PM(2.5) in the atmosphere, and it should be not excepted that sarcoidosis may be a sensitive individual reaction to the PM(2.5) inhaled from the atmosphere.</p>

Clinicopathologic study of sinonasal inflammatory myofibroblastic tumor / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunophenotype and ultrastructural features of sinonasal inflammatory myofibroblastic tumors (IMT).</p><p><b>METHODS</b>The clinical and histologic features of 5 cases of sinonasal IMT were reviewed. Immunohistochemical study for vimentin, MSA, SMA, calponin, h-caldesmon, desmin, ALK, fibronectin, CK, S-100 and Ki-67 was carried out. Ultrastructural examination was also performed in two of the cases.</p><p><b>RESULTS</b>The patients age ranged from 28 to 62 years (mean = 43 years). The male-to-female ratio was 2:3. The clinical presentation included nasal obstruction, nasal discharge, nasal bleeding, facial pain, facial swelling, toothache and tear overflow. All of the 5 patients suffered from disease relapses; and 4 of them had recurrences for more than 5 times. One patient had lymph node metastasis and 3 patients died of the disease. Histologically, the tumor cells were arranged in interlacing fascicles and sometimes haphazard in fashion. They were spindly in shape, cytoplasm eosinophilic with mild nuclear atypia and a low mitotic activity. The intervening stroma was myxoid in appearance accompanied by lymphocyte and plasma cell infiltration, abundant blood vessels and focal collagenized areas. In 3 of the recurrent cases, the tumor cells displayed increased nuclear atypia and mitotic activity (average about 5 to 6 per 10 high-power fields), accompanied by patchy necrosis, less inflammatory cell infiltration and focal sarcomatous changes. Immunohistochemical study showed that the tumor cells were diffusely positive for vimentin. SMA, MSA, calponin and fibronectin were variably expressed. Desmin was weakly positive in 1 case. The staining for h-caldesmon, ALK, S-100 and CK was negative. The Ki-67 proliferation index increased with tumor recurrences. Electron microscopy revealed abundant rough endoplasmic reticulum and dense body formation in the cytoplasm. There were an increased amount of collagen fibers in the stroma.</p><p><b>CONCLUSIONS</b>IMT rarely occurs in nasal cavity and paranasal sinuses. The tumor is prone to local invasion and recurrences, with subsequent progression to frank malignancy and distant metastasis, resulting in high mortality and poor prognosis. Complete surgical resection remains the main modality of treatment.</p>

Clinicopathologic study of malignant tumors in head and neck region complicated by fungal infection / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features of malignant tumors in head and neck region complicated by fungal infection.</p><p><b>METHODS</b>Twenty-one cases of malignant tumors occurring in head and neck region complicated by fungal infection were retrieved from the archival file. The light microscopic findings were reviewed. Histochemical (for PAS and GMS) and immunohistochemical (for MUC5B) studies were carried out. Fungal culture results were available in 13 of the 21 cases.</p><p><b>RESULTS</b>The age of the patients ranged from 12 to 72 years (median = 48 years). The male-to-female ratio was 17:4. Eight cases (38.1%) were complicated by invasive fungal sinusitis, with orbital involvement in 6 cases and brain involvement in 1 case. The primary tumors in such cases included leukemia (n = 7) and nasopharyngeal carcinoma (n = 1). The fungi belonged to Zygomycete in 5 cases and Aspergillus in 3 cases. These patients had history of chemotherapy/radiotherapy or antibiotics usage. The remaining 13 cases of fungal infection often affected necrotic tumor tissue in nasal cavity, paranasal sinuses, pharynx, larynx and palate. The fungi involved were Aspergillus (n = 6) and Candida (n = 4). Seven of such patients had received radiotherapy. Fungal culture was positive in 9 cases. Fourteen patients had follow-up information available and six of them died of the disease.</p><p><b>CONCLUSIONS</b>Malignant tumors occurring in head and neck region can be complicated by fungal infection. Invasive fungal sinusitis (due to Zygomycetes and Aspergillus) often occurs in patients with leukemia, tends to involve orbit and is associated with poor prognosis. On the other hand, Aspergillus and Candida are the commonest fungi found in the necrotic tumor tissue. Pathologic examination remains the hallmark in confirming the diagnosis and fungal typing.</p>

Manifestation and treatment of lipoid proteinosis in larynx / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the manifestation, characteristics and treatment of lipoid proteinosis (LP) in larynx.</p><p><b>METHODS</b>Sixteen cases of LP with hoarseness as the first sign were reported. The onset was in the newborn period in 10 cases. The upper eyelids were infiltrated in all cases, 13 of them reported an age of onset older than 6 - 8 years. The laryngeal behaviors and its treatment, multisystem manifestations, and characteristics of histopathology were evaluated.</p><p><b>RESULTS</b>One patient had moderate hoarseness, and the others had severe hoarseness. Videolaryngoscopy revealed thickening of the interarytenoid region and irregularities along the rims and the surface of the vocal folds due to yellowish papules. Oral tissues showed yellow-white infiltrates in 13 cases (81.3%). Whitish moniliform papules on the upper eyelids were found in all cases. Pock-like or acneiform scars were particularly evident on the face and the limbs in 14 cases (87.5%). Histologically, it was characterized by deposition of hyaline material in the submucosa and dermis of the eyelid or larynx with periodic acid-Schiff-positive and Congo red stain-negative. Eight patients underwent microlaryngosurgery for the excision of deposits in the vocal folds. The vocal function was significantly improved after surgery.</p><p><b>CONCLUSIONS</b>One of the most common features of lipoid proteinosis is hoarseness since infancy with laryngeal involvement. LP patients also display skin or mucosa infiltration of multiple systems. Microlaryngosurgical excision of the deposits in the vocal fold could improve the voice.</p>

Pathologic diagnosis of specific infections in upper aerodigestive tract / 中华病理学杂志

<p><b>OBJECTIVE</b>To find a fast and simple method for detection of specific pathogens in upper aerodigestive tract.</p><p><b>METHODS</b>Sixty-one cases of specific infections in upper aerodigestive tract encountered during a 10-year period in Beijing Tongren Hospital were retrospectively studied. Six histochemical stains, including PAS, Giemsa, Gram, methylene blue, modified Warthin-Starry and acid-fast stains were applied. The morphology of different pathogens was studied and the staining patterns were compared.</p><p><b>RESULTS</b>There were 23 cases of pharyngeal treponemal infection, 10 cases of short treponemal infection, 4 cases of mycobacterial infection, 4 cases of infection by rhinoscleroma bacilli, 1 case of sinonasal fungal infection, 1 case of combined infection of bacteria and Oidium albicans, 2 cases of tonsillar Actinomycetes and 16 cases of non-specific bacterial infections. Both pharyngeal treponemal infection and infection by rhinoscleroma bacilli could be detected by modified Warthin-Starry stain. As for sinonasal fungal infection, PAS, Giemsa and modified Warthin-Starry stains were useful in differentiating different types of fungi. Mycobacteria were best demonstrated by conventional acid-fast stain.</p><p><b>CONCLUSIONS</b>Special histochemical stains performed on histologic sections are useful for diagnosing specific infections in upper aerodigestive tract.</p>

Relationship between primary ocular adnexal mucosa-associated lymphoid tissue lymphoma and eye infection / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the role of pathogenic microorganisms commonly associated with chronic eye disease, including Chlamydia psittaci, Chlamydia trachomatis, Chlamydia pneumoniae, herpes simplex virus (HSV) type 1 and type 2, and adenovirus type 8 and type 19, in the development of primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma in Chinese patients.</p><p><b>METHODS</b>Sixty-eight archival cases of primary ocular adnexal lymphoproliferative lesions, including 38 cases of MALT lymphoma, 3 cases of non-MALT lymphoma and 27 cases of chronic inflammation, were enrolled into the study. DNA was extracted from the paraffin-embedded tissue samples. The presence of DNA of C. psittaci, C. trachomatis, C. pneumoniae, HSV type 1, HSV type 2, adenovirus type 8 and adenovirus type 19 were analyzed by multiplex touchdown enzyme time-release polymerase chain reaction (TETR-PCR).</p><p><b>RESULTS</b>All of the specimens yielded PCR products of over 100 base pairs and were thus suitable for TETR-PCR screening of infectious agents. The prevalence of DNA of C. psittaci, C. trachomatis and adenovirus type 19 were 0 in MALT lymphoma, non-MALT lymphoma and chronic inflammation. There were 2 cases positive for C. pneumoniae DNA, amongst the 38 cases of MALT lymphoma studied (5.3%, 2/38). HSV type 1, HSV type 2 and adenovirus type 8 DNA was found in each of the 3 patients with chronic inflammation.</p><p><b>CONCLUSION</b>The study indicates that C. psittaci, C. trachomatis, C. pneumoniae, HSV type 1, HSV type 2, adenovirus type 8 and adenovirus type 19 probably play little role in the pathogenesis of ocular adnexal MALT lymphoma in Chinese patients.</p>

Clinicopathologic evaluation of 36 cases of allergic fungal sinusitis / 中华病理学杂志

<p><b>OBJECTIVE</b>To characterize clinicopathological features of allergic fungal sinusitis (AFS).</p><p><b>METHODS</b>Thirty-six cases of AFS were retrieved from the department archival files of Beijing Tongren Hospital from 2002 to 2006. AB-PAS, GMS and MUC5B stain were performed using paraffin-embedded tissues of the cases. Ten cases with available fresh diagnostic tissue were investigated by electron microscopy.</p><p><b>RESULTS</b>Patients included 21 males and 15 females. The age of patients ranged from 11 to 53 years. Atopy was very common in these patients. On plain CT scans, the affected nasal sinuses were filled with soft tissue shadow with patchy hyperdensity. The bony sinus wall showed areas of pressure erosion. Skin antigen tests showed fungal positivity in 31 of 36 cases. Serum levels of the total IgE and/or the specific fungal IgE were elevated in 20 cases. The eosinophil quantity was elevated in 23 cases. Fungal culture was positive in 10 cases. Gross examination showed thick putty secretions within the lesions. Light microscopy showed typical "eosinophilic mucin". Fungal elements were seen with AB-PAS, GMS and MUC5B stains. Electron microscopy demonstrated degranulation by the eosinophils.</p><p><b>CONCLUSIONS</b>"Eosinophilic mucin" is the typical histopathological feature of AFS. AB-PAS, GMS and MUC5B staining methods can used to detect fungal species in mucin. Accurate diagnosis of AFS requires correlations among clinical findings, radiologic examinations, laboratory tests and histopathologic features. However, the ultimate diagnosis requires a histopathologic confirmation.</p>

Olfactory neuroblastoma with unusual structures: a clinical pathologic study / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate unusual pathological features of olfactory neuroblastoma (ONB) and its correlation with the clinical prognosis.</p><p><b>METHODS</b>Totally 40 cases of ONB were studied using histology and immunohistochemistry techniques. All the cases of ONB were graded according to Hyams Grading system.</p><p><b>RESULTS</b>ONB consisted of small round tumor cells growing in nests or lobules separated by fibrovascular septa. Characteristically, there were neurofibrillary intercellular matrices and Homer-Wright or Flexner-Wintersteiner rosette formation. The unusual structures including epithelial components such as mucous or squamous cell nests which were found in 45.0% (18/40), and 15.0% (6/40) respectively. In addition, 3 cases showed an in-situ form with invasion of tumor into olfactory epithelium, and there was exogenous papillary proliferation seen in 2 cases. Log-rank survival analysis demonstrated that Hyams Grading had no statistical correlation with the prognosis. The presence of necrosis was correlated with a poor prognosis (P = 0.016) while the presence of mucous cells was correlated with a good prognosis (P = 0.011).</p><p><b>CONCLUSIONS</b>Unusual pathological structures including epithelial structures, in-situ invasion of tumor tissue into the involving olfactory epithelium and exogenous papillary proliferation can be found in ONB, suggesting that ONB may originate from the undifferentiated basal cells of olfactory epithelium, through bipotential differentiation. The presence of tumor necrosis in ONB is a poor prognostic indicator while the presence of mucous cells suggests a good prognosis.</p>

Significance of MUC5B antibody in differential diagnosis between Aspergillus species and Mucorales of fungal sinusitis / 中华病理学杂志

<p><b>OBJECTIVE</b>To differentiate between Aspergillus species and Mucorales of fungal sinusitis by immunohistochemistry.</p><p><b>METHODS</b>Formalin-fixed paraffin-embedded tissue blocks of 66 cases of fungal sinusitis were retrieved from the archival files of Department of Pathology of Beijing Tongren Hospital during the period from 2001 to 2006. The samples included 29 cases of fungal balls, 12 cases of allergic fungal sinusitis, 24 cases of chronic invasive fungal sinusitis and 1 case of acute invasive fungal sinusitis. The types of fungi were 44 Aspergillus species (31 cases of A. fumigatus, 7 cases of A. flavus and 6 cases of A. terreus) and 22 Mucorales (14 cases of Mucor species and 8 cases of Rhizopus species). Immunohistochemistry was performed with MUC2, MUC5AC and MUC5B antibodies. The results were compared with histochemical study for periodic acid-Schiff (PAS) and Grocott methenamine silver (GMS) stains.</p><p><b>RESULTS</b>Immunohistochemical study for MUC5B showed that the positive rate of Aspergillus species was 90.9%, in contrast to 4.5% in Mucorales (P < 0.001). The expression of MUC2 and MUC5AC was completely negative, whereas PAS and GMS stains were positive in all cases.</p><p><b>CONCLUSION</b>MUC5B antibody appears to be a useful immunohistochemical marker for identifying fungal types in tissue sections, especially in distinguishing between Aspergillus species and Mucorales in fungal sinusitis.</p>

Clinicopathologic study of sinonasal teratocarcinosarcoma and its contrast with olfactory neuroblastoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, diagnosis and differential diagnosis of sinonasal teratocarcinosarcoma (SNTCS) and olfactory neuroblastoma (ONB), and to discuss the histogenesis and possible relationship between SNTCS and ONB.</p><p><b>METHODS</b>Seven cases of SNTCS and 34 cases of ONB were retrieved from the pathological archives together with one case each of malignant teratoma and immature embryonic tissue at 8 weeks were collected from Beijing Tongren Hospital. The clinicopathologic features were analyzed and immunohistochemical staining was performed on paraffin sections.</p><p><b>RESULTS</b>Six of the SNTCS patients were male and one was female. The patients age range was 25 to 69 years (mean age 46). Four cases were initial presentation and three were recurrences. Histologically, the tumor shows multiple tissue components derived from three germ layers. There were mixture of teratoma-like tissue and carcinosarcoma. The components include fetal clear cell squamous epithelium derived from ectoderm. Glandular and tubular structures and ciliated columnar epithelium derived from endoderm. Fibroblasts, striated muscle, smooth muscle, cartilage and osteoid matrix derived from mesoderm. The carcinoma component exhibited mostly adenocarcinoma and squamous cell carcinoma, whereas the sarcoma component mostly exhibited rhabdomyosarcoma, leiomyosarcoma, and fibrosarcoma. In addition, carcinoid, and primitive mesenchymal tissue and the ONB component were also seen. The morphological characteristics of SNTCS comprised fetal clear cell squamous epithelium, carcinosarcoma and the ONB component. By immunohistochemistry, the epithelial component and cells with epithelium differentiation were positive for cytokeratin (pan) and EMA. The ONB component was positive for Syn, NSE, CD99, NF and CgA to different degrees. Neurofibril bundles were positive for S-100, and Flexner-Wintersteiner rosettes expressed cytokeratin (pan) and EMA. The spindle cells expressed vimentin, SMA, desmin, myosin and myoglobin. The primitive mesenchymal tissue expressed vimentin, and the mucoid materials and glycogen were positive for PAS. GFAP was negative in all cases. The 34 cases of ONB, included 18 men and 16 women, the age ranged from 12 to 72 years (mean 42.8 years). Microscopically, the tumor shows epithelial nests, net of angioma-like fibrous connective tissues, small round and spindle cells, glandular, squamous-like cells, and cells of rhabdomyoblastic differentiation, Homer-Wright and Flexner rosette, bundles of neurofibrils, etc. NSE and CgA were expressed in small cells. S-100 protein was positive in the areas of bunches of neurofibril. Cytokeratin (pan) was positive in epithelial cells. Myoglobin was positive in the cells of rhabdomyoblastic differentiation. The single case of immature malignant teratoma exhibited primitive nerve tissue, but fetal clear cell squamous epithelium was not found. In the immature embryonic tissue, rudimentary organs were formed, with fetal clear cell squamous epithelium lining present on the nasal and oral cavities surface.</p><p><b>CONCLUSIONS</b>SNTCS is a rare and aggressive malignant neoplasm. Most of ONB are low-grade malignant tumors. Morphological differences are the most important basis to make differentiate SNTCS from ONB. As SNTCS may demonstrate a multiplicity of structures and pleomorphism, inadequate sampling at biopsy, therefore, may lead to errors in diagnosis. No evidence show that SNTCS are derived from germ cells and sinonasal teratoid carcinosarcoma may be a more proper name. SNTCS probably arises from primitive totipotential cells of olfactory/sinonasal membrane, and the relationship between SNTCS and ONB needs further study.</p>