Immunohistochemical Re-evaluation Research Articles

High expression of progesterone receptor may be an adverse prognostic factor in oestrogen receptor-negative/progesterone receptor-positive breast cancer: results of comprehensive re-evaluation of multi-institutional case series

Oestrogen receptor (ER)-negative (-) progesterone receptor (PgR)-positive (+) is the least common combination of steroid receptor expression observed in breast cancer. There are many controversies regarding the actual existence of ER-/PgR+ phenotype. In the current study, we aimed to perform comprehensive immunohistochemical re-evaluation of ER-/PgR+ breast cancers from multiple institutions. A total of 135 cases of ER-/PgR+ breast cancer were collected from 11 institutions from the period 2006-2020 and subsequently stained with three clinically validated anti-ER antibody clones: SP1 (Roche), 1D5 (Dako), and EP1 (Dako), and two anti-PgR antibody clones: 636 (Dako), and 1E2 (Roche). Clinicopathological characteristics of confirmed and re-categorised cases were analysed. Seventy-six cases retained the original ER-/PgR+ phenotype, including 21 HER2+ and 55 HER2- tumours. Forty-seven cases were ER+ with at least one anti-ER antibody, and 12 cases were re-categorised as double-negatives across all anti-ER and anti-PgR antibodies. No significant differences in survival were observed between groups in the HER2+ category. In the HER2- cohort, confirmed ER-/PgR+, ER+ tumours with discrepant ER staining, and triple negatives had inferior overall survival compared to concordant ER+ cases. Progesterone receptor expression in >20% of cells was identified as an adverse prognostic factor in ER-/PgR+/HER2- breast cancer in a multivariable model adjusted by stage (HR 5.0, 95% CI 1.3-19.2, p=0.019). We performed one of the largest validation studies so far on ER-/PgR+ breast cancer and confirmed the existence of this subgroup. Moreover, we identified high PgR expression as an adverse prognostic factor.

Invasive Breast Carcinoma with Neuroendocrine Differentiation: A Single-Center Analysis of Clinical Features and Prognosis.

Introduction Invasive breast cancer with neuroendocrine differentiation is a rare subtype of breast malignancy. Due to frequent changes in the definition of these lesions, the correct diagnosis, estimation of exact prevalence, and clinical behaviour of this entity may be challenging. The aim of this study was to evaluate the prevalence, clinical features, and outcomes in a large cohort of patients with breast cancer with neuroendocrine differentiation. Patients Twenty-seven cases of breast cancer with neuroendocrine differentiation have been included in this analysis. Twenty-one cases were identified by systematic immunohistochemical re-evaluation of 465 breast cancer specimens using the neuroendocrine markers chromogranin A and synaptophysin, resulting in a prevalence of 4.5%. A further six cases were identified by a review of clinical records. Results Median age at the time of diagnosis was 61 years. 70% of patients had T2 – 4 tumors and 37% were node-positive. The most common immunohistochemical subtype was HR-positive/HER2-negative (85%). 93% were positive for synaptophysin and 48% for chromogranin A. Somatostatin receptor type 2A status was positive in 12 of 24 analyzed tumors (50%). Neuroendocrine-specific treatment with somatostatin analogues was administered in two patients. The 5-year survival rate was 70%. Conclusions Breast cancer with neuroendocrine differentiation is mostly HR-positive/HER2-negative and the diagnosis is made at a higher TNM stage than in patients with conventional invasive breast carcinoma. Moreover, breast cancer with neuroendocrine differentiation was found to be associated with impaired prognosis in several retrospective trials. Due to somatostatin receptor 2A expression, somatostatin receptor-based imaging can be used and somatostatin receptor-targeted therapy can be offered in selected cases.

Dermatofibrosarcoma protuberans: clinicopathologic presentation in Nigerians.

IntroductionDermatofibrosarcoma protuberance (DFSP) is in general a rare low grade malignant sarcoma and possesses a tendency for local recurrence. It has a site predilection for the trunk. Occurrence in the facial area is extremely rare. Ample knowledge of its clinical, histological and biologic characteristics is vital for accurate and prompt recognition.MethodsOver 13 years, clinicohistologic information of cases was retrieved. Histological and immunohistochemical re-evaluation were performed to re-confirm diagnosis. Data collected and analyzed with SPSS Statistics version 20 were presented as frequency tables, charts and proportions as appropriate.ResultsOf 191 soft tissue sarcomas, a total of 28 cases were diagnosed as DFSP (14.7%). Facial types occurred in 3 cases (1.6%). Tumour had age and site predilections for the 4th decade and trunk respectively. There was an equal gender distribution among cases. Most common clinical presentation was in form of painless protruding nodular mass. General histologic presentation revealed cellular lesions composed of spindle to oval neoplastic cells arranged in a storiform pattern. Mitotic figures were rare. All cases showed positive expressions to CD34.ConclusionFacial DFSP is rare among Nigerians. Its clinical appearance may mimic other common benign lesions of the head and neck region often resulting in misdiagnoses. A comprehensive knowledge of its clinical and histologic presentations and biologic behavior, combined with its identification with the aid of advanced histologic and radiographic techniques results in prompt confirmatory diagnosis. Appropriate treatment should include adequate surgical excision techniques combined with adjuvant radiotherapy or chemotherapy.

Morphological and Immunohistochemical Reevaluation of Tumors Initially Diagnosed as Ovarian Endometrioid Carcinoma With Emphasis on High-grade Tumors.

Ovarian endometrioid carcinomas (OEC) of low grade have characteristic morphologic features, but high-grade tumors can mimic high-grade serous and undifferentiated carcinomas. We reviewed tumors initially diagnosed as OEC to determine whether a combination of pathologic and immunohistochemical features can improve histologic subclassification. Tumors initially diagnosed as OEC were reviewed using World Health Organization criteria. We also noted the presence of associated confirmatory endometrioid features (CEFs): (i) squamous metaplasia; (ii) endometriosis; (iii) adenofibromatous background; and (iv) borderline endometrioid or mixed Mullerian component. A tissue microarray was constructed from 27 representative tumors with CEF and 14 without CEF, and sections were stained for WT-1, p16, and p53. Of 109 tumors initially diagnosed as OEC, 76 (70%) tumors were classified as OEC. The median patient age was 55 years, and 75% of patients were younger than 60 years. Ninety-two percent presented with disease confined to the pelvis, and 87% of tumors were unilateral. The median tumor size was 11.8 cm. Only 3% of tumors were high grade (grade 3of 3). Eighty percent of cases had at least 1 CEF, and 59% had at least 2 CEFs. Eleven percent overexpressed p16, 0% overexpressed p53, and 3% expressed WT-1. Only 10% of patients died of disease at last follow-up. Thirty-three (33) tumors, or 30% of tumors originally classified as endometrioid, were reclassified as serous carcinoma (OSC). The median patient age was 54.5 years, and 59% of patients were younger than 60 years of age. Only 27% had disease confined to the pelvis at presentation, 52% of tumors were unilateral, and the median tumor size was 8 cm. Associated squamous differentiation, endometrioid adenofibroma, and endometrioid or mixed Mullerian borderline tumor (CEFs) were not present in any case, but 6% of patients had endometriosis. Approximately one half of the reclassified OSC demonstrated SET-pattern morphology (combinations of glandular, cribriform, solid, and transitional cell-like architecture) and were immunophenotypically indistinguishable from OSCs with papillary architecture. Sixty percent of OSC overexpressed p16, 50% overexpressed p53, and 82% expressed WT-1. At last follow-up, 52% had died of disease. Compared with OSC, OEC patients more frequently presented below 60 years of age (P=0.046), had low-stage tumors (P<0.001), were more frequently unilateral (P<0.001), more frequently had synchronous endometrial endometrioid carcinomas (P<0.001); and had no evidence of disease at last follow-up (P<0.001). Their tumors were of lower grade (P<0.001), had more CEFs (P<0.001), and less frequently overexpressed p16 and p53 (P=0.003 and P<0.001, respectively) and less frequently expressed WT-1 (P<0.001). This analysis emphasizes the diagnostic value of CEFs, the presence of a low-grade gland-forming endometrioid component, and WT-1 negativity, as valid, clinically relevant criteria for a diagnosis of OEC. Glandular and/or cribriform architecture alone may be seen in both OECs and OSCs and are therefore not informative of diagnosis. Further study is needed to elaborate the characteristics of the exceedingly rare high-grade OEC.

Cartilage regeneration after spheroid-based autologous chondrocyte implantation (ACI) : structural re-evaluation in second-look biopsies in five patients

Event Abstract Back to Event Cartilage regeneration after spheroid-based autologous chondrocyte implantation (ACI) : structural re-evaluation in second-look biopsies in five patients Christoph Brochhausen1, 2, David Grevenstein1, Volker Schmitt1, Jakob Grevenstein1 and C James Kirkpatrick1 1 University Medical Centre, REPAIR-lab, Institute of Pathology, Germany 2 University Hospital, REPAIR-lab, Institute of Pathology, Germany Background: Despite several tissue engineering-based strategies to treat articular cartilage damage there is a lack of structural re-evaluation of the regenerated tissue. Autologous chondrocyte implantation (ACI) is a clinically used strategy to treat cartilage defects. In the light of 10-15% of transplant failures a detailed analysis of the composition of the regenerated tissue is mandatory. We re-evaluate the regeneration of hyaline articular cartilage after spheroid-based ACI in re-biopsies in five patients. Methods: In this case series, we analysed biopsies of five patients, who had received a spheroid-based ACI after traumatic lesions of the hyaline cartilage in the knee. Biopsies were taken between 6 and 16 months after ACI. Every patient gave the indication for a second look arthroscopy due to secondary pathologies, independent of the initial defect. Fine needle biopsies were analysed histologically (HE, alcian-blue), immunohistochemically (collagen II, collagen X, lubricin, aggrecan), as well as ultrastructurally. Results: Histology revealed a completely avascular cartilage tissue with a homogeneous extracellular matrix and cells with a round, chondrocytic phenotype in each of these five case. The apical cells were often characterized by a flatter form, which is typical for the layer-based architecture of the tissue. Basally, a strict cartilage-bone border, without incorporating blood-vessels, could be observed. The subchondral bone showed neither bleeding, necrosis nor hypertrophy. There were no signs of degenerative change, such as myxoid matrix degeneration or the presence of fibrocytic cells. In the alcian-blue stain, a blue-colored extracellular matrix was noticeable, which indicates a high content of proteoglycans. The extracellular matrix was homogeneous and did not contain streaky or fibrillar areas. The immunohistological reaction with the anti-collagen II antibody produced a continuous brown colored regenerated tissue, which proves the presence of collagen II. The staining reaction for collagen X was negative in every case. As was the case for collagen II, the reaction for aggrecan showed a brown-colored extracellular matrix, which indicates positivity. The anti-lubricin-antibody showed positive cells in nearly every specimen. Ultrastructural analysis revealed already in the spheroid collagen fibres which were in contact with chondrocytes. In addition, the regenerated tissue showed ultrastructurally the normal chondrocyte phenotype with large amounts of typically arranged collagen fibres. Conclusion: The present study represents the first histological and immunohistochemical re-evaluation of the spheroid-based ACI in humans and undelines the regeneration of typical articular cartilage. One reason for these good results could be the preservation of the chondrocytic phenotype and the detection of collagen fibres already within the spheroids. Further clinico-pathological studies are needed to compare the structural outcome of matrix-assisted with the spheroid-based chondrocyte transplantation. Keywords: cell phenotype, clinical application Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Bone substitutes in clinics Citation: Brochhausen C, Grevenstein D, Schmitt V, Grevenstein J and Kirkpatrick C (2016). Cartilage regeneration after spheroid-based autologous chondrocyte implantation (ACI) : structural re-evaluation in second-look biopsies in five patients. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.02923 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Christoph Brochhausen David Grevenstein Volker Schmitt Jakob Grevenstein C James Kirkpatrick Google Christoph Brochhausen David Grevenstein Volker Schmitt Jakob Grevenstein C James Kirkpatrick Google Scholar Christoph Brochhausen David Grevenstein Volker Schmitt Jakob Grevenstein C James Kirkpatrick PubMed Christoph Brochhausen David Grevenstein Volker Schmitt Jakob Grevenstein C James Kirkpatrick Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Immunohistochemical Reevaluation of Carbonic Anhydrase IX (CA IX) Expression in Tumors and Normal Tissues

To immunohistochemically evaluate the carbonic anhydrase IX (CA IX) expression on 1,551 cases of tumors and normal tissues from various organs. Immunohistochemical evaluation of the expression of CA IX was performed on 1,125 malignant tumors, 69 benign neoplasms, and 322 normal tissues on tissue microarray sections and 18 intrahepatic cholangiocarcinomas (ICCs) and 17 hepatocellular carcinomas (HCCs) on routine sections. There was overexpression of CA IX in clear cell renal cell carcinoma (CRCC) (88%, 68/77). Twenty-six (90%) of 29 ICCs were positive. In contrast, only 5 (15%) of 34 HCCs were focally positive. No staining was seen in chromophobe renal cell carcinoma (ChRCC), oncocytoma, seminoma, or carcinomas of the breast, thyroid, or prostate. All normal renal tubules except one case showed no staining. These data demonstrate the diagnostic utility of CA IX in (1) differentiating CRCC from ChRCC and oncocytomas, (2) distinguishing low-grade CRCC from normal renal tubules in small samples, (3) separating ICC from HCC, and (4) identifying metastatic CRCC from other metastases with clear cell features.

Clarifying the Spectrum of Driver Oncogene Mutations in Biomarker-Verified Squamous Carcinoma of Lung: Lack of EGFR/KRAS and Presence of PIK3CA/AKT1 Mutations

There is persistent controversy as to whether EGFR and KRAS mutations occur in pulmonary squamous cell carcinoma (SQCC). We hypothesized that the reported variability may reflect difficulties in the pathologic distinction of true SQCC from adenosquamous carcinoma (AD-SQC) and poorly differentiated adenocarcinoma due to incomplete sampling or morphologic overlap. The recent development of a robust immunohistochemical approach for distinguishing squamous versus glandular differentiation provides an opportunity to reassess EGFR/KRAS and other targetable kinase mutation frequencies in a pathologically homogeneous series of SQCC. Ninety-five resected SQCCs, verified by immunohistochemistry as ΔNp63(+)/TTF-1(-), were tested for activating mutations in EGFR, KRAS, BRAF, PIK3CA, NRAS, AKT1, ERBB2/HER2, and MAP2K1/MEK1. In addition, all tissue samples from rare patients with the diagnosis of EGFR/KRAS-mutant "SQCC" encountered during 5 years of routine clinical genotyping were reassessed pathologically. The screen of 95 biomarker-verified SQCCs revealed no EGFR/KRAS [0%; 95% confidence interval (CI), 0%-3.8%], four PIK3CA (4%; 95% CI, 1%-10%), and one AKT1 (1%; 95% CI, 0%-5.7%) mutations. Detailed morphologic and immunohistochemical reevaluation of EGFR/KRAS-mutant "SQCC" identified during clinical genotyping (n = 16) resulted in reclassification of 10 (63%) cases as AD-SQC and five (31%) cases as poorly differentiated adenocarcinoma morphologically mimicking SQCC (i.e., adenocarcinoma with "squamoid" morphology). One (6%) case had no follow-up. Our findings suggest that EGFR/KRAS mutations do not occur in pure pulmonary SQCC, and occasional detection of these mutations in samples diagnosed as "SQCC" is due to challenges with the diagnosis of AD-SQC and adenocarcinoma, which can be largely resolved by comprehensive pathologic assessment incorporating immunohistochemical biomarkers.

Small invasive colon cancer with systemic metastasis: A case report

BackgroundRecently, especially in Japan, several researchers have suggested that colorectal cancer can develop not only through an adenoma-carcinoma sequence but also from normal mucosa via a de novo pathway, and that these de novo cancers have more aggressive malignant potential. We report a case of aggressive colon cancer resulting in systemic metastasis despite small tumour size.Case PresentationA 35-year-old woman presented at the referring hospital with swelling of the left cervical lymph node. Biopsy of the lymph node revealed metastatic adenocarcinoma; however, CT scan and mammography were unable to identify the site of the primary lesion. She was diagnosed with unknown primary cancer and referred to our hospital for further examination. Immunohistochemical reevaluation showed the cervical lymph node biopsy specimen to be positive for CDX2 and CK20 and negative for CK7 expression, leading us to suspect the presence of a primary colorectal cancer. We performed a total colonoscopy, and detected a small protruding lesion in the transverse colon. The tumour was only 12 mm in diameter, with a central depressed component and a severely thickened stalk, which suggested direct cancer invasion of the deep submucosa. We concluded that this lesion was the site of origin of the metastasis despite the small tumour size, and performed diagnostic endoscopic mucosal resection. The lesion was found to have an intramucosal cancer component, demonstrating that this lesion represented primary colon cancer. The patient was referred to the gastrointestinal oncology division for systemic chemotherapy.ConclusionsIn this case, immunohistochemical findings strongly suggested the existence of a colorectal cancer. The non-polypoid gross appearance of the tumour suggested that it can originate de novo , thus providing a valuable case in support of the aggressive malignant potential of a de novo colorectal cancer pathway.

Tumor burden of sentinel lymph node metastasis in Merkel cell carcinoma

The applicability of sentinel lymph node biopsy (SLNB) for staging has been recognized in association with Merkel cell carcinoma (MCC). However, the concept of tumor burden with respect to MCC involving sentinel lymph nodes has not been analyzed. Our aim was to assess tumor burden in the sentinel lymph nodes of MCC patients. This retrospective study analyzes 15 consecutive patients and 57 sentinel lymph nodes. Immunohistochemical re-evaluation of the sentinel lymph nodes was performed. Positive sentinel node metastases were classified according to type of invasion, size and tumor burden. Occult metastases were observed in 36% of the patients. Maximal sizes of the metastatic foci and tumor burden in the lymph nodes were larger than what has been reported in melanoma and breast cancer sentinel lymph nodes. The distribution of metastatic cells in the involved lymph nodes was mostly combination type with only one marginal sinus type. False-negative lymph nodes were found in 30% of the patients. Immunohistochemical re-evaluation decreased this figure to 22%. Metastatic foci and tumor burden in positive sentinel lymph nodes seem to be larger in MCC than in melanoma and breast cancer sentinel nodes. Statistical analysis showed no correlation between tumor burden and survival. In the context of MCC, false-negative sentinel lymph nodes can and should be limited by using immunohistochemistry.

Role of lymph node dissection in the treatment of urothelial carcinoma of the upper urinary tract: Multi-institutional relapse analysis and immunohistochemical re-evaluation of negative lymph nodes

Aim To determine the role of lymph node dissection (LND) in the treatment of urothelial carcinoma (UC) of the upper urinary tract (UUT). Patients and methods [Study-1] A retrospective multi-institutional study evaluated 293 patients undergoing predominantly nephroureterectomy for UC of the UUT. Of 293 patients, 267 patients had pure UC and 26 demonstrated other histological components. Regarding the pathological node status, 130 patients had pN0 disease, 141 patients had pNx disease and 22 patients had pN+ disease. The sites of initial recurrence and time to first recurrence were reviewed. The sites of recurrence were classified as locoregional or distant recurrence. The relationship between node status and future recurrence was analyzed. [Study-2] Fifty-one patients treated by nephroureterectomy at Hokkaido University Hospital were included. All had LND and all LNs were negative on hematoxylin and eosin staining. We re-evaluated the presence of micrometastasis in LND specimens by anti-cytokeratin immunohistochemistory. Results [Study-1] Of 293 patients, 76 developed disease relapse. Regional lymph node recurrence was the most common site (34 patients). On multivariate analyses that adjusted for the effect of tumor stage and tumor grade, pNx (skipping LND) was an adverse factor not only for locoregional recurrence, but also for distant relapse. [Study-2] Immunohistochemistry identified micrometastases in 7 (14%) of 51 patients. Regarding survival, 5 of these 7 patients with micrometastases were alive at last follow-up. Conclusions On relapse analysis, skipping LND was an adverse factor not only for locoregional recurrence, but also for distant relapse. Immunohistochemistry detected micrometastases in about 14% of patients previously diagnosed as pN0. These findings further support a potential therapeutic benefit of LND by eliminating micrometastases.

Solid pseudopapillärer Tumor des Pankreas bei einem 12jährigen Mädchen – 7 Jahre Follow-up und histopathologische Reevaluation

BACKGROUND: Solid-pseudopapillary tumor of the pancreas (so-called Frantz tumor) is a rare neoplasm of typically benign behavior, predominantly occurring in young females, but very rare in girls. METHODS: The clinical course of a 12-year-old girl suffering from such a tumor is presented and diagnostic and therapeutic methods are pointed out. Furthermore the relevance of the histological tumor classification respectively of recent immunohistochemical investigations with consideration of the actual literature will be discussed. The mentioned girl was admitted to our department of pediatric surgery because of upper abdominal pain, persistent for 12 hours. Initial examinations (physical examination, routine laboratory parameters, and abdominal ultrasound) showed a well-defined, spheric tumor (8 cm in diameter) with solid and cystic areas, without hints for metastases. The combination of the two facts – young girl and solid-cystic lesion of the pancreas – made us think about a Frantz tumor. By performing CT and MRT of the abdomen this diagnosis was hardened. In fact the patient underwent a Kausch–Whipple operation (modified by Traverso–Longmire) to perform a radical tumor removal. RESULTS: The clinical and radiological diagnosis was confirmed by histological examination of the tumor, i.e., the lesion was valued as solid-pseudo papillary neoplasm of the pancreas. Neither short-term or long-term surgical complications, nor metastases have been recorded in the follow-up (7 years up to now). An immunohistochemical reevaluation of the tumor material was carried out on occasion of the recent follow-up (April 2009); new aspects concerning tumor genesis could not be realized. CONCLUSIONS: Solid-pseudo papillary tumors of the pancreas are rare tumors. The majority of these tumors show benign behavior; very few malignant clinical courses have been reported. Despite rare occurrence of the tumor clinical presumption diagnosis possible, based on the fact that these tumors particularly affect young females and radiological findings show a tumor with solid and cystic parts. Radical tumor resection is the therapeutic method of choice. Because of the risk of injuring of the tumor an enucleation is discussed controversial. Despite special immunohistochemical and genetic examinations (influences of estrogenic hormones?) the origin of the tumor remains unknown.

Prevalence and Origin of Amyloid in Kidney Biopsies

We aimed to reassess renal amyloidosis in kidney biopsies with a focus on possibly misclassified or unclassified cases and changes in the prevalence of different amyloid types. Two hundred thirty-three kidney biopsies obtained from 231 patients diagnosed with amyloid during the period from 1990 to 2007 years were included in this retrospective study. Amyloid was identified by Congo red staining and polarization microscopy. Immunohistochemical classification was made with antibodies directed against AA amyloid, apolipoprotein A1, fibrinogen, lysozyme, lambda-light chain, kappa-light chain, beta2-microglobulin, transthyretin, and amyloid P-component. Amyloid was present in each biopsy as vascular, tubulo-interstitial and/or glomerular deposits. Immunoglobulin light chain-derived (AL) amyloidosis was most prevalent and diagnosed in 123 (53.2%) patients. It was categorized into AL amyloid of lambda-light chain (ALlambda) [105 (85.4%) patients] and kappa-light chain origin (ALkappa) [10 (8.1%)]. The amyloid deposits of 8 (6.5%) patients were not clearly distinguishable into ALlambda amyloid or ALkappa amyloid and categorized as AL amyloid, not otherwise specified. Reactive systemic amyloid A (AA) amyloidosis was the second most common type and was found in 93 patients (40.3%). Overall 7 patients were found to suffer from fibrinogen A alpha-chain-[amyloid of fibrinogen (AFib); 4 (1.7%) patients], transthyretin-[amyloid of transthyretin (ATTR); 2 (0.9%)], or apolipoprotein A1-derived (AApoAI) amyloidosis [1 (0.4%)]. In 8 patients (3.4%) the amyloid deposits remained unclassifiable. After additional immunostaining and further clinical information the diagnoses of 12 patients (5.1%) were modified (2 ALlambda amyloid, 4 ALkappa amyloid, 1 amyloid unclassified, 3 mixed-type amyloidosis, AA+ATTR, ALlambda+ATTR, and ALkappa+ATTR, 1 AFib, and 1 AApoAI). Although the histologic and immunohistochemical reevaluation confirmed the classifications in 221 (95.7%) patients. Renal amyloidosis is most commonly of ALlambda-origin, followed by AA amyloidosis. AFib amyloidosis was found to be the most prevalent type of hereditary renal amyloidosis, illustrating the necessity of a thorough classification of the amyloid proteins.

Fibrosarcoma in infants and children: a retrospective analysis - overdiagnosis in earlier years.

During a 30-year period, 22 patients considered to have a fibrosarcoma (FS) were treated. In a retrospective study the clinicopathologic findings were summarized. With histologic and immunohistochemical re-evaluation, the diagnosis was confirmed in 8 cases. For 6 further patients FS was very probable but specimens were not available. In 8 cases the diagnosis was revised and benign lesions were found in 7. Two patients with irresectable tumors died (infantile FS, FS of mesentery and retroperitoneum). After repeated local recurrences and spread on the affected extremity, an amputation was life-saving in 1 boy. In earlier years many tumors were classified as FSs. Today, immunohistochemistry and molecular-biological methods are valuable tools to clearly identify these tumors. Wide local excision or en-bloc resection without sacrificing any significant function of the part should be the primary form of treatment in infants. Primary re-excision after incomplete excision should have priority over any adjuvant treatment. Preoperative chemotherapy may avoid incomplete resection or mutilation in cases with extended congenital FS.