Invasive breast lobular carcinoma with extracellular mucin: a clinicopathological analysis / 中华病理学杂志

Objective@#To study the clinicopathological features of invasive lobular carcinoma (ILC) of the breast with extracellular mucin and outcomes of patients.@*Method@#Clinicopathological features and clinical follow-up (39-123 months and a median follow-up of 55 months) of seven ILC with extracellular mucin were obtained. Hematoxylin-and-eosin (H&E) and immunohistochemistry (IHC) stained sections were reviewed, and fluorescence in situ hybridization (FISH) assay was performed for tumors with HER2 IHC 2+. Patient prognosis was analyzed and literatures related to ILC with extracellular mucin were reviewed.@*Results@#All seven patients were female, aged from 43 to 73 years (median age, 55 years). The tumors ranged in size from 1 to 5 cm (median size 2 cm). All seven cases were of histological grade 2. Most areas of the tumors presented with the morphology of classic ILC, and variable amount of extracellular mucin were observed focally. In six cases, part of the tumor cells contained intracellular mucin, and the nucleus were pushed to one side of the cells, creating the impression of signet-ring cells. Two patients had lymph node metastases at diagnosis, and developed liver and bone metastases at 38th and 48th month, respectively, after surgery, and died at 48th and 123th month, respectively. While the other five patients, except one lost to follow-up, had been disease-free during the follow-up period. IHC results showed estrogen receptor (ER) and progesterone receptor (PR) positivity in 7/7 and 6/7 cases, respectively. Tumors of six patients were HER2 IHC 0/1+. The remaining one was HER2 IHC 2+, while FISH assay revealed HER2 gene amplification in that tumor. The proportion of cases with HER2-positivity was 1/7. The proliferation index Ki-67 ranged from less than 5% to 30%, and Ki-67 less than or equal to 10% were in 5/7 cases. According to the 2013 St. Gallen International Expert Consensus on breast cancer, all tumors were of luminal types; of those, two were luminal A and five were luminal B.@*Conclusions@#ILC with extracellular mucin tends to occur in women over 50 years old. All tumors in the study are grade 2 classic ILC, with signet-ring cells as a common feature. All seven tumors are classified as luminal types, with luminal B as the main molecular subtype.

Clinicopathological study of BCOR rearrangement in high grade endometrial stromal sarcoma / 中华病理学杂志

Objective@#To investigate clinicopathological, cytogenetic features and differential diagnoses of high grade endometrial stromal sarcoma (HGESS) with BCOR gene rearrangement.@*Methods@#Five cases of HGESS with BCOR rearrangement were collected from consultant files (2016-2018) at Fudan University Shanghai Cancer Center. Interphase FISH was performed using a dual color break-apart probe. The clinical data, histologic features and immunohistochemical findings were reviewed.@*Results@#All 5 cases occurred in adult women with a median age of 48 (range, 45-55) years. Abdominal pain and abnormal vaginal bleeding were the most common symptoms. Microscopically, the tumors showed mainly tongue-like and/or intersecting myometrial invasion. Stromal myxoid matrix and/or collagen plaques were prominent in all the cases. Most tumors consisted of uniform, haphazard fascicles of short spindle cells with mild to moderate nuclear atypia. Mitotic figures and necrosis were easily identified. Significant nuclear pleomorphism was not seen. Most tumors were rich in thick-walled small vessels. Prominent perivascular tumor cell whorling seen in conventional low-grade endometrial stromal sarcoma was not seen. All tumors expressed CD10 with only focal or absent desmin, SMA and/or h-caldesmon staining. ER or PR expression was seen in 4 tumors and 1 tumor showed both marker expression. Diffuse cyclin D1 was present in 2 tumors. BCOR immunoreactivity was present with strong staining in 3 cases and moderate staining in 1 case respectively. Ki-67 index ranged from 10% to 30%. Fluorescence in situ hybridization confirmed chromosomal aberration of BCOR gene in all tumors, that were previously diagnosed as myxoid leiomyosarcoma (2 cases), spindle cell uterine sarcoma (2 cases) and low-grade endometrial stromal sarcoma (1 case). Limited follow-up information revealed that 3/5 patients developed tumor recurrence, metastasis or death within one year.@*Conclusion@#BCOR rearranged HGESS has distinct morphological features and aggressive clinical behavior. In the presence of significant overlapping morphologic features between BCOR rearranged HGESS and other myxoid uterine mesenchymal tumors, especially myxoid leiomyosarcoma, molecular analysis is essential for accurate diagnoses.

Expression of SMARCA4(BRG1) and SMARCB1(INI1) in dedifferentiated and undifferentiated endometrial carcinomas and their correlations with clinicopathological features / 中华病理学杂志

Objective@#To investigate the expression of SMARCA4 (BRG1) and SMARCB1 (INI-1) protein in endometrial dedifferentiated carcinoma (DDC) and undifferentiated carcinoma (UDC), and their correlation with clinicopathologic features.@*Methods@#Clinicopathological information was gathered for 26 cases of DDC and UDC and consulting hospitals from January, 2006 to December, 2018 in Fudan University Shanghai Cancer Center, including 10 cases of DDC and 16 cases of UDC. Morphologic features and diagnosis were reviewed by two pathologists. Immunohistochemistry for expression of BRG1 and INI1 protein was performed. The correlations with clinicopathologic features were analyzed.@*Results@#BRG1 and INI1 loss were present in 14 of 26 cases of DDC/UDC, including 12 BRG1-deficient cases and 2 INI1-deficient cases, respectively. Six cases demonstrated variable amounts of rhabdoid cells in 14 BRG1/INI1-deficient cases, and only 1 case showed rhabdoid cells in the 12 intact expression cases. However, there was no significantly statistical difference (P=0.060). Age, invasive depth, lymph node status and FIGO stage were not associated with the expression of the BRG1 and INI1 (P=0.437, P=0.672, P=0.242, P=0.348). Remarkably, the BGR1/INI1-deficient patients had worse survival than those with intact expression (4.7 vs. 22.9, P=0.033).@*Conclusion@#BRG1/INI1-deficient is observed in approximately half of DDC and UDC. Identification of these tumors is clinically relevant due to their more aggressive behavior and poor prognosis. Hence, BRG1 and INI1 immunohistochemical stains should be performed for DDC and UDC in order to help the pathologists to distinguish these tumors from other carcinomas, and to predict the clinical prognosis.

Clinicopathologic analysis of primary carcinoid of the ovary / 中华病理学杂志

Objective@#To describe the clinicopathologic features, diagnosis and differential diagnosis of ovarian carcinoid tumors.@*Methods@#A retrospective chart review was performed of all patients diagnosed with primary ovarian carcinoid tumors at Fudan University Shanghai Cancer Centre from 2007 to 2017.@*Results@#The histologic analysis of these carcinoid tumors revealed 3 were insular, 1 was trabecular, 1 was mucinous, and 10 were strumal. Histologic features of insular and trabecular carcinoid were similar to other parts of the neuroendocrine tumor. Strumal carcinoid was composed of thyroid tissue intimately admixed with carcinoid tumor, showing trabecular pattern. Mucinous carcinoid was resembles Krukenberg tumor. Most ovarian carcinoid tomours were diffusely positive with at least one neuroendocrine marker, especially synaptophysin (14/14) and CD56(9/10). The median follow-up time was 53 months, 1 patient with squamous-cell carcinoma of cervixrecur rence in vaginal after 37 months, and only 1 patient died of disease. The remaining patients were disease-free survival.@*Conclusions@#Primary carcinoid of the ovary is a very rare low grade malignant monodermal teratomas and somatic-type tumours arising from a dermoid. The diagnosis and differential diagnosis mainly relies on the histopathologic characteristics and the immuno-phenotype. Primary ovarian carcinoid almost always exhibit a benign clinical behavious except mucinous carcinoid.

Clinicopathologic study of infiltrating epitheliosis of the breast / 中华病理学杂志

Objective@#To evaluate the morphological and immunohistochemical features of infiltrating epitheliosis and its differential diagnosis.@*Methods@#Nine consultation and routine cases of infiltrating epitheliosis diagnosed from January 2015 to December 2016 in Fudan University Shanghai Cancer Center were collected. All tissues were formalin-fixed paraffin-embedded and routinely HE stained. The HE slides were reviewed. Immunohistochemical staining of CKpan, CK7, CK19, CK5/6, CK14, p63, SMMHC, Calponin, ER, PR, HER2, Ki-67 and S-100 protein was performed using Ventana BenchMark automated immunostainer.@*Results@#The morphological features of infiltrating epitheliosis included: (1) Florid proliferation of epithelial cells forming solid nests or papillary, glandular and cord-like pattern. The proliferative cells possessed nuclei of varying size and shape without atypia. (2) The stroma was altered, showing varying degrees of fibrosis or sclerosis. (3) The proliferative epithelial nests might flow into the spaces within small ducts and lobules at the periphery of the lesion, resulting in pseudo-infiltration. Immunohistochemically, infiltrating epitheliosis was non-uniformly positive for ER/PR, and was positive for high molecular weight CK5/6 and CK14. Myoepithelial markers p63, SMMHC and Calponin demonstrated intact, partial or entire loss of myoepithelial cells around the epithelial nests. The loss of myoepithelial markers staining was more frequent at the periphery of the lesion. The most important differential diagnoses included invasive ductal carcinoma, ductal carcinoma in situ (DCIS), and low grade adenosquamous carcinoma, etc.@*Conclusions@#Infiltrating epitheliosis is an important pseudo-infiltrating lesion. The lack of atypia, non-uniform ER/PR expression, positivity for high molecular weight cytokeratins, and the intact to partial to entire loss of myoepithelial markers around the proliferating cell nests are the key points to differentiate it from invasive carcinomas and DCIS.

Values of JAZF1 gene rearrangement detected by fluorescence in-situ hybridization in diagnosis of endometrial stromal tumours / 中华病理学杂志

Objective@#To investigate the role of JAZF1 gene rearrangement in the diagnosis and differential diagnosis of endometrial stromal sarcomas by fluorescence in situ hybridization (FISH).@*Methods@#JAZF1 gene rearrangement was analyzed by FISH in 129 cases of ESS diagnosed from January 2008 to December 2016 including 105 cases of low-grade endometrial stromal sarcoma (LG-ESS), 21 cases of high-grade endometrial stromal sarcoma (HG-ESS) and 3 cases of undifferentiated uterine sarcoma (UUS). Sixteen cases of the related tumours in uterus were also collected as control group. The results were compared with our previous studies of JAZF1/JJAZ1 fusion gene in ESS by RT-PCR.@*Results@#Detection of JAZF1 gene rearrangement by FISH was successfully analyzed in 144 cases. JAZF1 gene alteration was detected in 63 cases, all of which were LG-ESS, with an overall positivity of 60.6% (63/104), while no JAZF1 gene rearrangement was found in all other cases. JAZF1 gene rearrangement was present in LG-ESS with classic histology (69.3%, 52/75), smooth muscle differentiation (2/10), sex cord-like differentiation (4/5), fibromyxoid change (1/5), clear cell change (0/1), skeletal muscle differentiation (0/1), and schwannoma-like palisading pattern (0/1). The different components in all the cases of LG-ESS with variant histology had the clonal origin, with or without JAZF1 gene alteration. Compared to the results of JAZF1/JJAZ1 fusion gene by RT-PCR, the positive rate of JAZF1 gene rearrangement in LG-ESS by FISH (61.9%, 26/42) was significantly higher than that of RT-PCR (30.0%, 12/40; P<0.01).@*Conclusions@#JAZF1 gene rearrangement is present only in LG-ESS, but not in HG-ESS, UUS or other related tumours in uterus. The frequency of JAZF1 gene rearrangement varies between classic LG-ESS and different morphologic variants. It is frequently, but not consistently, present in classic LG-ESS and less often positive in variant cases. The results of JAZF1 gene alterations in LG-ESS with different morphologic variants support the contention that the endometrial stromal and their variant morphologic components have the same clonal origin. Detection of JAZF1 gene rearrangement by FISH is very useful for the diagnosis and differential diagnosis of ESS.

Correlation between androgen receptor expression and surrogate molecular subtypes in invasive breast carcinoma / 中华病理学杂志

Objective@#To investigate androgen receptor(AR)expression in invasive breast carcinoma and the correlation with surrogate molecular breast carcinoma subtypes.@*Methods@#Immunohistochemical staining of AR and other biomarkers was performed in a cohort of 870 cases of primary invasive breast carcinomas collected from August to December, 2016. The association of AR expression with different histological and surrogate molecular subtypes was analyzed.@*Results@#The positive expression rate of AR in the immunohistochemistry-based surrogate subtypes was 96.3%(207/215) for Luminal A, 89.8%(378/421) for Luminal B, 82.4%(75/91) for HER2 overexpression and 37.1%(53/143) for triple negative breast carcinoma, with significant differences among the four groups (P<0.01). AR correlated positively with the expression of ER(P<0.01), PR(P<0.01), HER2(P=0.007), GATA3(P<0.01), GCDFP15(P<0.01)and mammaglobin(P<0.01), while negatively with the expression of Ki-67(P<0.01), CK5/6(P<0.01)and CK14(P<0.01).@*Conclusions@#AR exhibits a high expression in invasive breast carcinoma, which is mainly correlated with ER-positive breast carcinoma. Regardless of the relatively low expression rate, AR is a potential therapeutic target in triple negative breast carcinoma.

Clinicopathologic features of cystic hypersecretory lesion of the breast / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunophenotype and differential diagnosis of cystic hypersecretory lesion (CHL) of the breast.</p><p><b>METHODS</b>Clinicopathologic and follow-up data of six cases of breast CHL in 2010-2013 were collected and reviewed.Immunohistochemical and mucinous staining was performed.</p><p><b>RESULTS</b>All six patients were female, age ranged from 37 to 71 years (average 49.3 years). Three cases were cystic hypersecretory hyperplasia (CHH), the other three cases were cystic hypersecretory carcinoma (CHC). Clinically the lesions presented as either breast mass or mammographic calcification.Grossly, the cystic hypersecretory lesions were poorly circumscribed, with multiple colloid containing cysts on the cut surface. Microscopically, the remarkable feature was numerous enlarged cysts which contained densely eosinophilic homogeneous secretion similar to the colloid seen in thyroid follicles, and calcification was seen in the cyst in one case. The secretion was D-PAS and mucicarmine positive. The lining epithelium of the cysts was uniformly flat, cuboid or columnar, and arranged in a monolayer. The cells may be arranged in turfs, solid or micropapillary patterns in CHH.In cases with dysplasia, the epithelium showed cytological and structural atypia, but the usual morphology of atypical dutal hyperplasia such as arcades, rigid bridges or cribriform pattern was less common. The three CHC included two invasive ductal carcinomas (IDC) and one ductal carcinoma in situ (DCIS).In CHL, there was immunoreactivity to S-100 protein, CK5/6 and CK14.Of the three CHCs, ER and PR were expressed in only one IDC.No HER2 expression was identified in the two invasive CHCs.One patient was lost to follow-up, and the rest were uneventful at 18 months.</p><p><b>CONCLUSIONS</b>CHL of the breast is a rare pathological entity. Multiple colloid-filled cysts is a unique histological feature. The epithelium of CHL may show usual hyperplasia, dysplasia or carcinoma.</p>

Metastases to the breast from non-mammary malignancies: a clinicopathologic study of 28 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic characteristics and differential diagnosis of the metastases to the breast from non-mammary malignancies.</p><p><b>METHODS</b>Twenty-eight cases were collected from 2004 to 2012;microscopic pathologic examinations and immunohistochemistry (EnVision method) were performed.</p><p><b>RESULTS</b>(1) All except one patients were female, ranging from 16 to 77 years old (average 45.8 years). Twenty-six (92.9%) patients initially presented with the primary site lesions; while the other two (7.1%) patients initially presented with breast lesions. The mean interval from primary diagnosis to detection of metastatic breast lesions was 32 months (0-228 months). Fifteen patients (53.6%) had other metastases detected simultaneously or preceded the breast lesions. (2) Macroscopically, all the tumors were relatively circumscribed, with a mean diameter of 4.0 cm (0.6-12.0 cm). The histological types of the corresponding primary tumors were as follows: eight (28.6%) cases from lung adenocarcinoma, five (17.8%) from high-grade ovarian serous carcinoma, three (10.7%) from gastric adenocarcinoma, two (7.1%) from rectal adenocarcinoma, one (3.6%) from pancreatic neuroendocrine carcinoma, one (3.6%) from prostatic carcinoma, four (14.3%) from melanoma, and four (14.3%) from mesenchymal malignant tumors (three rhabdomyosarcomas and one epithelioid malignant peripheral nerve sheath tumor, MPNST). (3) Histologically, the metastatic tumors showed the morphologic characteristics of the primary tumors. Lymph-vascular invasion was observed in 19 cases. Immunohistochemical features of metastatic tumors were consistent with the primary tumors. Molecular markers for breast such as GCDFP15 and mammaglobin were negative. Metastatic tumors from lung adenocarcinoma expressed TTF-1 (8/8). Ovarian serous carcinoma metastases were positive for PAX8 (5/5) and WT1 (4/5). Gastric adenocarcinoma metastases were positive for CDX2 (3/3) and villin (1/3). Rectal adenocarcinoma metastases were positive for CDX2 (2/2). Pancreatic neuroendocrine tumor metastasis was positive for Syn and CgA (both 1/1). Prostate carcinoma metastasis was positive for AR, PSA and P504S (all 1/1). Melanoma metastases were positive for HMB45 (2/3) and S-100 protein (3/3). Rhabdomyosarcoma metastases were positive for vimentin, desmin and myoD1 (all 3/3). MPNST metastasis was positive for S-100 protein (1/1). (4) Follow-up data was available in 17 patients, with median follow-up time 54 months. The median survival from diagnosis to breast metastasis was 24 months.Seven of 17 patients died.</p><p><b>CONCLUSIONS</b>Metastases to the breast from non-mammary malignancies are rare and show pathologic features of primary tumors. It is usually presumed to be a primary breast carcinoma. Histopathologic features and clinical history in conjunction with the immunohistochemical results should be considered in differentiating a secondary mass from a primary breast carcinoma.</p>

Atypical vascular lesions after conservative surgery and radiation of breast cancer: report of a case and review of the literature / 临床与实验病理学杂志

Purpose To describe the clinical and pathological features of atypical vascular lesions (AVLs) after conservative surgery and radiation of the breast cancer,and to discuss the association with post-radiation angiosarcoma.Methods The clinical and pathological features in one case of AVLs was evaluated.The literatures were reviewed.Results The patient is a 57-yeAR~-old female who underwent a conservative surgery of the right breast because of a carcinoma.She received standard dose of radiation as adjuvant therapy.Three years later, multiple erythematous plaques developed around the former scar, which radiated to the nipple.Clinically,the plaques were considered as relapses of the carcinoma.However, fine needle aspiration gave negative results.Biopsy of one large plague revealed a circumscribed vascular lesion confined to the superficial dermis.It was composed of thin-walled anastomosing lymphatic vessels lined by attenuated endothelial cells.In focal areas, the vessels extended to the mid-dermis.Immunohistochemically, the endothelial cells were positive for CD31, CD34 and D2-40,with absent of α-SMA positive pericytes.Review of the breast tumor sections showed an invasive micropapillary carcinoma.Conclusions AVLs is a rare vascular lesion related with conservative surgery and post-radiation therapy of the breast.AVLs may represent as a precursor of breast angiosarcoma.Being familiar with the clinicopathologic characteristics of AVLs is important not only for the pathologists but also for the clinicians.