Objective:To investigate the clinicopathological characteristics, immunophenotypes, diagnostic criteria and differential diagnosis of atrophic kidney-like lesion (AKLL).Methods:Three cases of AKLL were collected from April 2021 to October 2023 at the Xiangya Hospital of Central South University, Changsha, Zhejiang Provincial People′s Hospital, Hangzhou and Ningbo Clinical Pathology Diagnosis Center, Ningbo, China. The clinical, morphological, and immunohistochemical characteristics were analyzed. Relevant literature was also reviewed. A targeted DNA-based next-generation sequencing (a panel of 150 genes) was performed on one of the three cases.Results:There were 1 female and 2 males, aged 30, 57, and 17 years (mean 34.6 years), respectively. The lesions were all incidentally identified during physical or imaging examination. Radiologically, they were all presented as a unilateral renal parenchymal mass. Grossly, the maximum diameters of the lesions were 1.8, 4.0, and 6.5 cm (mean 4.1 cm), respectively. The tumor cut-surfaces were sponge-like, multilocular cystic, and solid, respectively. At low magnification, the lesions were well-circumscribed, while a thick fibromuscular capsule was noted in cases 1 and 3. Cases 1 and 2 were composed of thin-walled cysts or follicular like structures of varying sizes, with the cyst wall lined by flattened and atrophic, or hobnail cells. The luminal spaces contained dense eosinophilic secretion and associated calcifications, while some cysts contained discohesive cells floating in the eosinophilic material. The tissue between the cysts showed predominantly small atrophic tubular structures. Case 3 was almost entirely composed of atrophic and collapsed tubular structures with focal cyst formation, imparting a solid sheets growth pattern under low magnification. Immunohistochemical staining revealed that the cyst lining cells and the intracystic floating cells were WT1 positive, PAX8 negative and CK7 negative, while the atrophic renal tubules were WT negative, PAX8 positive and CK7 positive. Targeted next-generation sequencing in case 1 showed no significant genetic abnormalities. All 3 patients underwent partial nephrectomy. No evidence of recurrence or metastasis was found with a follow-up of 17 to 36 months.Conclusions:AKLL is a rare and novel benign renal disease. It is easily misdiagnosed as a renal neoplasm grossly and histologically. Careful morphological observation combined with characteristic immunophenotypes can aid in its diagnosis and differential diagnosis.

Objective:To investigate the clinicopathological characteristics of ossifying fibromyxoid tumor (OFMT) with rare fusion subtypes.Methods:Three cases of OFMT with rare fusion subtypes, diagnosed and consulted in the Zhejiang Hospital, Zhejiang Provincial People′s Hospital, Hangzhou, China and Ningbo Clinical Pathology Diagnosis Center, Ningbo, China from January 2016 to December 2024 were collected. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and targeted RNA sequencing were performed to analyze the immunohistochemical and molecular genetic characteristics of these OFMT. Literature review was also conducted.Results:All three patients were male, with ages of 50, 74, and 58 years, respectively. The tumors were located in the left foot, left thigh, and left lumbar region, respectively, and all presented as slowly growing, painless masses in the skin or subcutaneous tissue. Grossly, the tumors measured 3.5 cm, 6.3 cm, and 5.0 cm in maximum diameter, respectively, with a grayish-white to grayish-yellow, solid, lobulated cut surface. One case exhibited a noticeable myxoid texture. Microscopically, one tumor was located in the superficial dermis, while the other two were in the subcutaneous tissue. The tumors were well-demarcated and showed a lobulated or multinodular growth pattern. None of the cases had a complete surrounding bony shell (only one case had very focal ossification). The tumor cells were monomorphic, short spindle-shaped, oval to epithelioid, and arranged in solid sheets, trabeculae, and small nests within a variably fibromyxoid stroma. Case 1 exhibited abundant pseudorosette-like structures formed by short spindle cells surrounding acellular fibrous stroma. Case 2 showed focal transition of epithelioid tumor cells into fasciculately arranged spindle cells, with extensive stromal hyalinization. Case 3 had a predominantly myxoid stroma with a rich network of thin-walled blood vessels. The tumor cells exhibited mild nuclear atypia with 1-3 mitotic figures per 50 high-power fields. All three cases showed diffuse and strong expression of CD10. Two of the three cases showed nuclear expression of TFE3, while one case showed diffuse and strong expression of desmin and S-100. Targeted RNA sequencing revealed PHF1 (ex12)::TFE3 (ex7) fusion in two cases and MEAF6 (ex5)::PHF1 (5′UTR) fusion in one case, which were further confirmed by FISH study. All three patients underwent tumor resection. Two showed no recurrence during follow-up periods of 98 months and 15 months, respectively, while one experienced local recurrence at 12 months postoperatively.Conclusions:OFMT with rare fusion subtypes often exhibits atypical histological and immunophenotypic features, and lacks a characteristic bony shell. Incorporating TFE3 into the diagnostic IHC panel greatly aids in screening for the cases with rare PHF1::TFE3 fusions. Familiarity with the histological and immunophenotypic characteristics, and differential diagnostic points of these rare OFMT subtypes, is essential for judicious use of molecular genetic tools in achieving a definitive diagnosis.

Objective:To investigate the clinicopathological characteristics, immunophenotypes, diagnostic criteria and differential diagnosis of atrophic kidney-like lesion (AKLL).Methods:Three cases of AKLL were collected from April 2021 to October 2023 at the Xiangya Hospital of Central South University, Changsha, Zhejiang Provincial People′s Hospital, Hangzhou and Ningbo Clinical Pathology Diagnosis Center, Ningbo, China. The clinical, morphological, and immunohistochemical characteristics were analyzed. Relevant literature was also reviewed. A targeted DNA-based next-generation sequencing (a panel of 150 genes) was performed on one of the three cases.Results:There were 1 female and 2 males, aged 30, 57, and 17 years (mean 34.6 years), respectively. The lesions were all incidentally identified during physical or imaging examination. Radiologically, they were all presented as a unilateral renal parenchymal mass. Grossly, the maximum diameters of the lesions were 1.8, 4.0, and 6.5 cm (mean 4.1 cm), respectively. The tumor cut-surfaces were sponge-like, multilocular cystic, and solid, respectively. At low magnification, the lesions were well-circumscribed, while a thick fibromuscular capsule was noted in cases 1 and 3. Cases 1 and 2 were composed of thin-walled cysts or follicular like structures of varying sizes, with the cyst wall lined by flattened and atrophic, or hobnail cells. The luminal spaces contained dense eosinophilic secretion and associated calcifications, while some cysts contained discohesive cells floating in the eosinophilic material. The tissue between the cysts showed predominantly small atrophic tubular structures. Case 3 was almost entirely composed of atrophic and collapsed tubular structures with focal cyst formation, imparting a solid sheets growth pattern under low magnification. Immunohistochemical staining revealed that the cyst lining cells and the intracystic floating cells were WT1 positive, PAX8 negative and CK7 negative, while the atrophic renal tubules were WT negative, PAX8 positive and CK7 positive. Targeted next-generation sequencing in case 1 showed no significant genetic abnormalities. All 3 patients underwent partial nephrectomy. No evidence of recurrence or metastasis was found with a follow-up of 17 to 36 months.Conclusions:AKLL is a rare and novel benign renal disease. It is easily misdiagnosed as a renal neoplasm grossly and histologically. Careful morphological observation combined with characteristic immunophenotypes can aid in its diagnosis and differential diagnosis.

Objective:To investigate the clinicopathological characteristics of ossifying fibromyxoid tumor (OFMT) with rare fusion subtypes.Methods:Three cases of OFMT with rare fusion subtypes, diagnosed and consulted in the Zhejiang Hospital, Zhejiang Provincial People′s Hospital, Hangzhou, China and Ningbo Clinical Pathology Diagnosis Center, Ningbo, China from January 2016 to December 2024 were collected. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and targeted RNA sequencing were performed to analyze the immunohistochemical and molecular genetic characteristics of these OFMT. Literature review was also conducted.Results:All three patients were male, with ages of 50, 74, and 58 years, respectively. The tumors were located in the left foot, left thigh, and left lumbar region, respectively, and all presented as slowly growing, painless masses in the skin or subcutaneous tissue. Grossly, the tumors measured 3.5 cm, 6.3 cm, and 5.0 cm in maximum diameter, respectively, with a grayish-white to grayish-yellow, solid, lobulated cut surface. One case exhibited a noticeable myxoid texture. Microscopically, one tumor was located in the superficial dermis, while the other two were in the subcutaneous tissue. The tumors were well-demarcated and showed a lobulated or multinodular growth pattern. None of the cases had a complete surrounding bony shell (only one case had very focal ossification). The tumor cells were monomorphic, short spindle-shaped, oval to epithelioid, and arranged in solid sheets, trabeculae, and small nests within a variably fibromyxoid stroma. Case 1 exhibited abundant pseudorosette-like structures formed by short spindle cells surrounding acellular fibrous stroma. Case 2 showed focal transition of epithelioid tumor cells into fasciculately arranged spindle cells, with extensive stromal hyalinization. Case 3 had a predominantly myxoid stroma with a rich network of thin-walled blood vessels. The tumor cells exhibited mild nuclear atypia with 1-3 mitotic figures per 50 high-power fields. All three cases showed diffuse and strong expression of CD10. Two of the three cases showed nuclear expression of TFE3, while one case showed diffuse and strong expression of desmin and S-100. Targeted RNA sequencing revealed PHF1 (ex12)::TFE3 (ex7) fusion in two cases and MEAF6 (ex5)::PHF1 (5′UTR) fusion in one case, which were further confirmed by FISH study. All three patients underwent tumor resection. Two showed no recurrence during follow-up periods of 98 months and 15 months, respectively, while one experienced local recurrence at 12 months postoperatively.Conclusions:OFMT with rare fusion subtypes often exhibits atypical histological and immunophenotypic features, and lacks a characteristic bony shell. Incorporating TFE3 into the diagnostic IHC panel greatly aids in screening for the cases with rare PHF1::TFE3 fusions. Familiarity with the histological and immunophenotypic characteristics, and differential diagnostic points of these rare OFMT subtypes, is essential for judicious use of molecular genetic tools in achieving a definitive diagnosis.

Objective:To investigate the clinicopathological characteristics, and prognosis of appendiceal goblet cell adenocarcinoma(GCA).Methods:The clinical and pathological data of 21 GCA cases were retrospectively analyzed, and their pathological morphology, immunohistochemical phenotype, genetic alteration and clinical treatment and prognosis were studied.Results:Most of the 21 patients showed appendicitis, with appendectomy alone or extensive resection of the tumor, followed by chemotherapy. There were 12 low-grade and 9 moderate and high-grade patients by pathological examination, and tumor cells express CEA, CK20, SATB-2, Syn(19/21), CgA(18/21), CD56(18/21), Ki67(+,10%-50%),and one patient had mutations in the BRAF gene.Depth of tumor infiltration ( r=0.716, P<0.001), and TNM stage ( r=0.816, P<0.001) were all positively correlated with the grade of GCA. After 19 to 98 months of follow-up, one patient relapsed and one patient died. Conclusions:Appendiceal GCA is a kind of tumor with bidirectional differentiation characteristics. Its morphology and biological behavior lineage are relatively broad, especially the high level is more aggressive, hence more active treatment should be adopted.

Human milk plays an irreplaceable role in nutrition, immune promotion and psychological development of infants.And it can also decrease the risk of infectious disease, overweight/obesity, diabetes and other diseases.Therefore, the guidelines of various countries advocate that human milk is the optimal choice for infants.However, cases of food allergy in infants fed with human milk are common in clinical practice.Some studies have found that there are some active food antigens in human milk, which can stimulate immune responses and cause allergic symptoms in infants.At present, the mechanism of food allergy in infants fed with human milk is not clear, and this paper is to review the progress in this field in recent years.

Objective: To investigate the molecular genetic and clinicopathologic characteristics, immunophenotypes, diagnostic and differential diagnostic features of myxoid angiomatoid fibrous histiocytoma (MAFH). Methods: Three cases of MAFH were collected from the archives of Zhejiang Provincial People′s Hospital between January 2015 to August 2018. The clinical and radiologic features, histomorphology, immunohistochemistry, molecular genetics and prognosis were analyzed. Results: Patients consisted of 2 women and 1 man aged 37 years, 46 years, and 57 years, respectively. The clinical manifestations of 3 patients were presented as a painless, slowly-enlarged mass with a duration ranging of 2 weeks, 2 months and 50 years. These tumors were located at the deep somatic soft tissue of extremities or limbs (right hip, left forearm, left wrist, respectively) and 2 were preoperatively considered as ganglion cyst or giant cell tumor of tendon sheath by imaging examinations. The diameter of circumscribed mass lesion was ranged from 3.0 to 7.5 cm, which exhibited a gray white to tan and gelatinous cut surface. Extensive hemorrhage and cystic changes were observed in 2 cases. Under low magnification, all tumors showed a dense fibrous pseudo-capsule with a peritumoral lymphoplasmacytic cuff and a multi-nodular growth pattern. Blood-filled cystic spaces were observed in 2 tumors. The myxoid stroma occupied 60.0%, 80.0% and 90.0% area of the entire tumor, respectively. Within the myxoid areas, tumor cells were oval to stellate and arranged in cord-like, microcystic and reticular growth patterns. Transitions of myxoid tumor components to more solid areas with typical histology of angiomatoid fibrous histiocytoma (AFH) were observed at least focally in all the three cases. The tumor cells exhibited minimal atypia and scarce mitoses (1 to 2/50 HPF) without necrosis, and prominently focal intracytoplasmic vacuoles were identified in one case. The results of immunohistochemistry staining showed that, 2/3 cases focally expressed desmin, 2/3 focally expressed epithelial membrane antigen (EMA), and 1/3 focally expressed CD99. The positive index of Ki67 was approximately 1% to 5%. Fluorescence in situ hybridization analysis showed that EWSR1 gene rearrangement occurred in all of the three cases. During the period of follow-up, one case showed local recurrence at 15 months, one case showed postoperative recurrence at 24 months, and the recurrent tumor slowly grew for 120 months until the second resection, without recurrence at the following 2 months. The left case showed a disease-free survival at 32 months. Conclusions MAFH is a rare subtype of AFH with a low-grade behavior and may lead to diagnostic confusions. Carefully searching for the typical AFH histomorphology and combining with EWSR1 gene rearrangement test can help to distinguish MAFH from other mimickers.

Objective:To investigate the clinicopathological characteristics and molecular genetics of atypical renal cysts.Methods:Six cases of atypical renal cysts were collected from Zhejiang Provincial People′s Hospital, Hangzhou, China, between February 2014 and February 2019. The clinicopathological characteristics and disease progression were analyzed. The 3p deletion and trisomy of chromosomes 7 and 17 were detected using fluorescence in situ hybridization (FISH).Results:All of the 6 patients were male, aged 43-63 years (median: 52 years). Preoperative Bosniak classification showed 4 cases of grade Ⅱ, 1 case of grade Ⅰ and 1 of grade Ⅲ. Histologically, atypical renal cysts appeared as unilocular or multilocular cysts, lined by multilayered flattened or cuboidal-shaped clear or eosinophilic cells. They often showed short papillary projections, and lacked solid or nodular growth of the lesional cells within the wall or septa of the cysts. Histologically, these cysts could be classified into three categories: acquired cystic disease-associated renal cell carcinoma (ACKD-RCC)-like (3 cases), clear cell type (2 cases), and eosinophilic papillary type (1 case). Two cases of ACKD-RCC-like atypical renal cysts were accompanied by clear cell renal cell carcinomas. On immunohistochemical staining, ACKD-RCC-like atypical renal cysts were focally CK7+/AMACR+/CD57+, the clear-cell type atypical renal cysts were CK7+/CAⅨ+, and eosinophilic papillary type atypical renal cysts were CK7+/AMACR+. FISH analyses showed that one case of ACKD-RCC-like atypical renal cysts had trisomy 17 and one case of clear cell type had 3p deletion, while no signal abnormality was detected in the other cases. The six patients were followed up for 13 to 70 months (median: 27 months), and no evidence of renal cell carcinoma was noted.Conclusion:Atypical renal cysts are a group of lesions that are heterogeneous in clinical, histological and immunophenotypical and molecular genetic features. FISH analyses suggest that a subset of the cases may be precursors of currently known renal cell carcinomas. Extensively sampling and careful observation of the histological characteristics of the cyst wall are important for distinguishing atypical renal cysts from extensively cystic renal cell carcinomas.

Objective: To investigate the histomorpholgic spectrum, immunophenotypic, and molecular genetic features of Sertoli cell tumor, not otherwise specified (SCT, NOS) of the testis. Methods: Seven cases of SCT, NOS of the testis were analyzed(4 from Peking University Third Hospital and 3 from Zhejiang Provincial People′s Hospital) between 2008 and 2017. The histopathologic features were examined based on HE staining, and EnVision method was used for immunohistochemistry staining of calretinin, inhibin, β-catenin, cyclinD1, CD10, CKpan, neuroendocrine markers, WT1, Melan A, vimentin, SALL4, GATA3, PAX8, and S-100 protein. Mutational analysis of exon 3 of the CTNNB1 gene by polymerase chain reaction (PCR)-amplified sequences and direct sequencing was performed. Results: Patients ages ranged from 22 to 65 years (mean 43 years). The clinical manifestation in all was a slowly enlarging, painless testicular mass.The maximum diameter of the tumor ranged from 1.5 cm to 3.0 cm (mean 2.1 cm). Sectioning usually disclosed a tan-gray to white mass with vague lobular cut-surface. Microscopically, the tumors were well circumscribed and non-encapsulated; the tumor cells were rearranged in multiple growth patterns from diffuse solid sheets to trabeculae and cords, ribbon and solid or hollow tubules setting in variable amount of acellular fibrous stroma. Two cases showed acellular collagenous stroma constituted >50% of the tumor confirming to the diagnosis of sclerosing SCT. One case demonstrated a prominent myxoid stromal change. The tumor cells typically had moderate amounts of pale to lightly eosinophilic cytoplasm, 2 tumors had variable cells with abundant lipid-rich cytoplasm, and 1 other tumor showed scattered aggregates of multinucleated tumor cells. The tumor cells were bland-appearing without any evidence of atypia, mitoses were noted in 2 tumors (both were 1/50 HPF), but necrosis was absent. Immunohistochemical staining results as follows: vimentin (diffuse, 7/7), CD10 (diffuse membrane, 7/7); diffuse β-catenin nuclear and cytoplasm staining in 5 of 7 cases, and all the 5 cases showed diffuse cyclin D1 nuclear staining, β-catenin membrane staining in 2 of 7 cases, CKpan (5/7, focal or diffuse), calretinin (focal, 5/6), inhibin (focal, 3/7), synaptophysin (focal, 2/6), CD56 (focal or diffuse, 4/5), WT1 (diffuse nuclear, 4/5), and S-100 protein (diffuse, 3/7), and chromogranin A, Melan A, PAX8, GATA3 and SALL4 all were negative. Molecular genetic studies of PCR and direct sequencing showed CTNNB1 mutations in 4 of 7 (4/7) cases, 4 of the four mutation-carrying cases showed diffuse β-catenin nuclear and cytoplasm immunoreactivity and diffuse cyclin D1 nuclear immunoreactivity in the tumor cells. Conclusions SCT, NOS of the testis typically shows significant heterogeneities in both morphology and immunohistochemistry, thus causing differential diagnostic confusions. Molecular analyses showed mutations of exon 3 of CTNNB1 in more than half of these tumors, and nuclear accumulation of β-catenin and over expression of cyclin D1 can be useful for the differential diagnosis of SCT, NOS.

Objective: To investigate the clinicopathologic features, diagnostic and differential diagnostic aspects of pigmented microcystic chromophobe renal cell carcinoma (ChRCC). Methods: Five cases of pigmented microcystic ChRCC were collected at Zhejiang Provincial People′s Hospital from January 2013 to January 2018. The clinical features, gross and histological appearances, immunohistochemistry and prognosis were analyzed and the relevant literature was reviewed. Results: There were 3 men and 2 women with age range of 45 years to 72 years (mean 57 years). All tumors were incidentally identified by imaging examinations. Grossly, the tumors were well-demarcated and showed diameters ranging from 1.8 cm to 4.0 cm(mean 2.9 cm). On cross section, the tumors were brown to gray tan with solid cut-surface mixed with multiple cysts of variable sizes. Hemorrhage was common, central scar was not seen. Microscopically, the tumors were composed predominantly of irregular and variable-sized microcystic or tubulocystic patterns, with extensive cribriform structures formation and focal adenomatous rearrangements seen in one case each, and focal pseudo-papillary structures (lacking true fibro-vascular cores) seen in two cases. Microscopic calcifications and psammoma bodies were present in all tumors. Four tumors composed mostly of eosinophilic cells whereas 1 predominated in plant-like cells. Brown pigmentations, either intracytoplasmic or extracytoplasmic, were noted in all five cases. The tumor cells had irregular, low-grade nuclei (Paner grade: 1) frequently with binucleation and perinuclar halos. Tumor necrosis or sarcomatous transformation was not seen. By immunohistochemistry, the tumor cells expressed CK, EMA, and E-cadherin diffusely and strongly in five cases; and CK7 and CD117 diffusely in four cases. They were negative for vimentin, CD10, CA9, AMACR/P504s, TFE3, HMB45, Melan A, S-100 protein, synaptophysin and chromogranin. Partial nephrectomies were performed for all five patients; there was no tumor recurrences or metastases at a follow-up of 2 to 55 months (mean, 17 months). Conclusions Pigmented microcystic ChRCC is a rare histological variant of ChRCC with relatively indolent behavior, and shows morphologic heterogeneity which can elicit a wide range of differential diagnoses. Careful attentions to search for typical features of classic ChRCC with the use of immunohistochemistry can help to distinguish this tumor from its many mimickers.