Clinical And Pathologica L Features Of Basosquamous Carcinoma: Analysis Of 10 Cases And Literature Review

BackgroundBasosquamous carcinoma(BSC)is a rare epithelial malignancy with features of both basal cell carcinoma(BCC)and squamous cell carcinoma(SCC).BSC is considered as aggressive tumor with a high risk of recurrence and metastases when compared with BCC.Because of its non-specific clinical manifestations and the limitations of local small biopsies,BSCs were often misdiagnosed as BCC or SCC or missed.Because BSC is rare and lacking of recognition,it is mostly reported in case reports and analyses of cases series Caucasian populations.No standard classification or guideline were made for diagnosis and treatment to date.ObjectiveWe analyze the clinical and pathological characteristics of basal squamous cell carcinoma aiming to improve the recognition of this tumor and decrease the possibility of misdiagnosis.And we aim to explore the factors that may affect the prognosis.MethodWe collected the clinical datas and tissue embedding paraffins of 10 BSC patients from Qilu Hospital of Shandong University during September 2016 to December 2021 for retrospectively analysis.BerEP4 and EMA are uesd for immunohistochemical staining.Relevant literatures were searched and then screened through CNKI,Wanfang Database and PUBMED,individual patient data(IPD)were extracted from the literatures.Graphpad Prism 7.0 were used for statistical analysis and graphing.P<0.05 was considered statistically significant.ResultPart Ⅰ.Analysis of 10 BSC cases1.General and ageThe ratio of male to female was 4:1,and the age ranged from 53 to 81 years,with an average age of 63.8±11.2 years.Tumors of 9 cases are all located on the head and face,and 1 case with multiple skin lesions on his head and trunk.The size the tumors range from 1.0 cm to 3.5 cm(median size 1.5 cm).The appearance of the skin lesions has no specificity.60%of patients have ulcers and no local invasion and infiltration are seen.2.Imaging examination and metastasisA total of 6 patients underwent whole-body imaging examination in our hospital.1 case was suspected of lymph node metastasis and distant metastasis(cranial),and 1 case(with multiple skin lesions)was suspected of lymph node metastasis.3.Treatment and prognosisA total of 6 patients were treated in our hospital.1 patient received Mohs microscopy surgery,and 4 patients received extended resection with a margin of 5mm.Patient with multiple lesions received partial resection and medicine treatment.No recurrence and metastasis were found up to now.4.Histological features and immunohistochemistryAll pathological slices comprise of BCC and SCC components when under microscope observation.The pathological manifestations of 4 patients(40%)show a mixed pattern,and 6 patients(60%)show intermediate pattern.The semi-quantitative H score between the positive control group and the BSC immunohistochemical staining results are not statistically different(p>0.05).The tissues show weakly positive staining for Ber-EP4 and EMA in overall appearance,even the staining distinction was not obvious in some mixed mode areas.Part Ⅱ:Literature review and analysesThrough literature search,a total of 62 case reports with relatively complete clinical data from February 1990 to December 2020 were included for analysis.1.Gender and age33 male patients(53.23%)and 29 female patients(46.77%)were included and the ratio of male to female is 1.14:1.The age range from 6 to 90 years old with a median age 62.5 years old and average age 62.32±17.96 years old.The age of 46 patients are over 50 years old,accounting for 74.19%.The age composition difference between male and female is not statistically significant p>0.05).Only 57 cases could estimate the approximate age of onset.The average age of onset was 57.20±18.54.The longest period from the discovery of the skin lesions to the diagnosis was confirmed was 25 years,and the shortest was just 1 month,the average is 5.02 years,and the median time is 3 years.2.InducementTumors of 20 cases(32.26%)are secondary to other skin diseases or have inducements.BSC may be secondary to xeroderma pigmentosum(3 cases),skin trauma or infection(7 cases),albinism(1 case),Verrucous epidermal dysplasia(2 cases),epidermal cyst(1 case),radiation dermatitis(1 case),arsenic keratosis(1 case),gigantic pore keratosis(1 case).3 cases have long-term sunlight Exposure history.Another 42 cases(67.74%)have no inducement.3.LocationLesions of 45 cases(72.58%)are located on the head and face,9 cases(14.52%)on the limbs,5 cases(8.06%)on the trunk,1 case(1.61%)on the anus and 2 cases(3.23%)have multiple lesions all over the body.4.Lesions size and clinical manifestationsThe tumor maximum diameters of 22 cases(35.48%)are less than 3cm,and that of another 40 cases(64.52%)were over 3cm(the size of patients with multiple BSCs was considered to be over 3cm).The appearance of tumors can mimic BCC and SCC.Thirty-six patients(58.06%)have ulcers in their skin lesions,and 26 patients don’t(41.94%).5.Location and invasion(infiltration)30 cases(48.38%of the total)have local infiltration,which can involve peripheral organs,nerves,blood vessels,muscles,skin and bones.The location of the disease was not statistically related to local invasion and infiltration(p>0.05).6.Tumor metastasisA total of 32 patients completed and recorded the imaging examination results to assess metastasis,of which 22 cases(68.75%)did not find metastasis.7 cases(21.88%)were with lymph node metastasis,and 3 cases(9.38%)with lymph node metastasis and distant metastasis.7.Histological features and invasion(infiltration)A total of 54 cases in the literature reports described the pathological pattern of the tumors and accompanied by pathological pictures.Among these,the pathological manifestations of 34 cases were considered to be mixed type(62.96%),15 cases for intermediate type(27.78%),and the remaining 5 cases(9.26%)are with two types coexistence.Pathological types are not statistically related to local invasion and infiltration significant(p>0.05).8.Treatment and prognosisA total of 41 cases recorded treatment and follow-up status with an average follow-up time of 15 months.28 patients received normal surgical resection,among which 4 cases had local recurrence,1 had local recurrence and distant metastasis after surgical and the recurrence rate was 14.28%.1 patient received surgical resection and lymph node dissection with no recurrence during follow-up.3 cases received surgical resection and postoperative radiotherapy,among which 1 case did not recurred but 2 cases had recurrence and metastasis and died finally.2 cases received surgical resection,lymph node dissection and postoperative radiotherapy with no recurrence during follow-up.1 case receive surgical resection,vismodegib and chemotherapy,but local recurrence occurred during follow-up.2 cases received Mohs microsurgery,and no recurrence during follow-up.2 cases received vismodegib treatment with no recurrence occurring during follow-up.2 patients with advanced BSC received conservative treatment and died finally.9.Factors affecting tumor metastasis and prognosisGender is not statistically related to tumor metastasis and prognosis(p>0.05).Tumor size is statistically related to both tumor metastasis and prognosis(p<0.05),which indicating tumors with size exceeding 3cm are more likely to have metastasis and poor prognosis.The appearance of ulcers in the skin lesions is statistically correlated with both tumor metastasis and prognosis(p<0.05),which indicating that tumors with ulcers are more likely to metastasize and have a poor prognosis.Race is statistically significant related to both local invasion and metastasis(p<0.05).Compared with Asian patients,European and American patients are more likely to have local invasion,invasion and metastasis.However,the difference between race and prognosis is not statistically significant.(P>0.05)Conclusion1.BSCs mainly occurs in elderly people.It is more common in male than female and can be secondary to traumatic stimulation,other skin tumors and genetic skin diseases.2.Most BSC arise in the region of the head and face,with perinasal areas being the most common location.The clinical manifestations are similar to squamous cell carcinoma and basal cell carcinoma results in high misdiagnosis rate and the diagnosis depends on pathological biopsy.3.The pathological manifestations of tumors can basically conform the classification of mixed and intermediate types.Tumor tissues can be immunohistochemically stained as positive by Ber-EP4 and EMA and the positive intensity difference between the two tumor components is not obvious.4.BSC has strong local invasion and infiltration ability,which can involve local organs,nerves,blood vessels,muscles and bones.Neither location nor the pathological type is statistical correlation to the invasion and infiltration of the tumor.5.Lymph node metastasis is more common,and distant metastasis is relatively rare.Tumors with ulcers or(and)with a maximum diameter exceeding 3 cm are more likely to metastasize and have a poor prognosis.Gender is not statistically related with metastasis and prognosis.Compared with Asian patients,European and American patients are more likely to have local invasion,invasion and metastasis.6.Surgery is the main treatment method,and it can also be combined with local radiotherapy,lymph node dissection and other treatments.Vismodegib can be used as a new treatment for poor prognosis BSC.