More Than Meets the Eye: A Case of Breast Cancer Switching from Being Luminal-Androgen-Receptor-Positive to Being Hormone-Receptor-Positive.

Triple-negative breast cancer (TNBC) represents about 15% of all breast cancers and is usually characterized by aggressive clinical behavior and a poor prognosis. Four TNBC subgroups have been previously defined with different molecular profiles: (i) luminal androgen receptor (LAR), (ii) mesenchymal (MES), (iii) basal-like immunosuppressed (BLIS) and (iv) basal-like immune-activated (BLIA). Among these, LAR is characterized by the expression of the androgen receptor (AR), and exhibits genomic characteristics that resemble luminal breast cancers, with a still undefined prognosis and clinical behavior. Here, we report a case of a woman affected by recurring LAR TNBC, which underwent phenotypic changes throughout its natural history. After the initial diagnosis of LAR breast cancer, the patient experienced local recurrence with strong expression of the estrogen receptor. Due to this finding, she started treatment with a CDK4/6-inhibitor and an aromatase inhibitor, followed by oral vinorelbine, both with dismal outcomes. Then, she received everolimus and exemestane, which determined temporary disease stabilization. An extensive NGS analysis of tumor tissue showed PIK3CA and HER2 mutations. Our case is consistent with previous reports of LAR breast cancer and underlines the potential utility of re-biopsy and molecular testing in breast cancer (BC), especially in rare subtypes.

The Role of Genital Tract Microbiome in Fertility: A Systematic Review.

The human microbiome plays a crucial role in determining the health status of every human being, and the microbiome of the genital tract can affect the fertility potential before and during assisted reproductive treatments (ARTs). This review aims to identify and appraise studies investigating the correlation of genital microbiome to infertility. Publications up to February 2021 were identified by searching the electronic databases PubMed/MEDLINE, Scopus and Embase and bibliographies. Only full-text original research articles written in English were considered eligible for analysis, whereas reviews, editorials, opinions or letters, case studies, conference papers, and abstracts were excluded. Twenty-six articles were identified. The oldest studies adopted the exclusive culture-based technique, while in recent years PCR and RNA sequencing based on 16S rRNA were the most used technique. Regardless of the anatomical site under investigation, the Lactobacillus-dominated flora seems to play a pivotal role in determining fertility, and in particular Lactobacillus crispatus showed a central role. Nonetheless, the presence of pathogens in the genital tract, such as Chlamydia trachomatis, Gardnerella vaginalis, Ureaplasma species, and Gram-negative stains microorganism, affected fertility also in case of asymptomatic bacterial vaginosis (BV). We failed to identify descriptive or comparative studies regarding tubal microbiome. The microbiome of the genital tract plays a pivotal role in fertility, also in case of ARTs. The standardization of the sampling methods and investigations approaches is warranted to stratify the fertility potential and its subsequent treatment. Prospective tubal microbiome studies are warranted.

Angioleiomyoma of the lumbo-sacral region with unusual keloid-like collagen fibers.

Angioleiomyoma is a benign soft tissue tumor which usually occurs in superficial or deep soft tissues. Only rarely does this tumor occur at unusual sites, including retroperitoneum. We present a rare case of lumbo-sacral angioleiomyoma in a 54-year-old man. Apart from this unusual site, the most striking morphological feature was the presence of numerous keloid-like collagen fibers interspersed among the fascicles of the neoplastic cells. Radiological, morphological and immunohistochemical features are presented, and differential diagnosis with its potential morphological mimickers is discussed.

Solitary fibrous tumor with atypical features of the paravesical space: benign clinical course at the 10-years follow-up. Report of a case and review of the literature.

Extra-pleural solitary fibrous tumor (SFT) is a relatively rare soft tissue neoplasm, with only rare cases reported in the pelvic cavity. Most SFTs are histologically benign, with only a few malignant cases reported in the literature so far. We report a rare case of SFT arising in the paravesical space of a 79-year-old man. Histologically the tumor corresponds to an "intermediate risk tumor" according to a risk stratification scheme for metastatic potential, which incorporates patient age, tumor size, mitotic activity and necrosis. Notably tumor showed a benign clinical course without evidence of local recurrence after a 10-years follow-up. Tumor was composed of both spindle and epithelioid cells variably set in a fibro-myxoid stroma, with focal pleomorphic, necrotic and highly mitotic (> 4 mitoses/10HPF) areas. Immunohistochemistry, showing a diffuse CD34 and STAT6 immunoreactivity, supported the diagnosis of SFT. The present case emphasizes that the clinical course of the pelvic SFTs with atypical morphological features is unpredictable on the basis of morphology alone, and thus the term "SFT with atypical features, including the risk stratification class" should be preferred to "malignant SFT".

Rare breast and subcutaneous metastases from pancreatic neuroendocrine tumor: a case report.

BACKGROUND: Neuroendocrine tumors are a group of rare neoplasms, and the pancreatic neuroendocrine tumors (PNETs) represent only 1-2% of all pancreatic malignant tumors. The most common sites of these tumors include the gastrointestinal tract, lung, adrenal gland, and thyroid gland. Moreover, the most common sites of PNET metastases are the lymph nodes, liver, spleen, and bone. A 40-year-old woman with pT3N1 PNET underwent surgical excision of the lesion (12 cm, at the level of the pancreatic body and tail). Postsurgical treatment included chemotherapy and radiation, both of which the patient showed a good tolerance for. After a 12-month disease-free interval, however, the patient reported the development of a lesion in her left breast and a small lesion in the left posterior region of her neck. The lesions were surgically excised, and the histological findings characterized both as pancreatic neuroendocrine metastatic poorly differentiated neoplasms (G3). A re-staging CT scan showed multiple metastases in the left axillary, clavicular, and latero-cervical lymph nodes, as well as diffuse osteolytic-osteoblastic bone metastases, almost mimicking the behavior of a primitive breast tumor. CONCLUSION: This case of breast and subcutaneous metastases from PNET should prompt awareness of potential metastatic lesions in unusual locations.

Solitary fibrous tumor occurring at unusual sites: A clinico-pathological series of 31 cases with emphasis on its wide morphological spectrum.

Solitary fibrous tumor (SFT) is a relatively rare mesenchymal fibroblastic tumor occurring most commonly in adults with no gender predilection. Although the pathological diagnosis of SFT is usually straightforward, some difficulties may occasionally arise mainly due to the wide morphological spectrum exhibited by this tumor. In the present paper we aimed to evaluate the unusual clinicopathological features in a series of 31 SFTs arising from parenchymal organs, superficial soft tissues and deep soft tissues. Our results emphasize that SFTs may occur anywhere, including unusual sites such as periosteum of the thoracic spine, mesorectal tissue, hepatic hilum, paravescial space, kidney and breast. Moreover, a wide morphological spectrum was observed in tumors included in our series. The most striking morphological features observed included: extensive lipomatous component, myxoid stromal changes, epithelioid cell component, metaplastic mature bone, neurofibroma-like, myxofibrosarcoma-like and pseudoalveolar-like areas. Additionally, multinucleated giant cells and sarcomatous dedifferentiation were also identified. Our paper emphasizes that SFT may occur in unusual anatomical locations and exhibits a wide morphological spectrum. Pathologists must be aware of these features to avoid confusion with other benign and malignant neoplasms that may show overlapping morphological features.

Evaluation of neoadjuvant chemotherapy effects on liver parenchyma in resected pediatric malignancies.

Neoadjuvant chemotherapy for colorectal liver metastases in adults is responsible for chemotherapy-associated liver injury (CALI), characterized by steatosis, steatohepatitis, and sinusoidal obstruction syndrome. These alterations cause delayed operation to reduce the risk of hemorrhage, portal hypertension, and hepatic failure. Children with hepatic malignancies usually receive neoadjuvant chemotherapy prior to surgery. The aim of this study was to evaluate retrospectively whether the CALI occurs in this pediatric population. This study evaluated patients referred since 1996 for hepatic malignancies who received hepatectomy after chemotherapy. Liver resection material was reviewed, in order to investigate the presence of morphological changes compatible with the CALI in the peritumoral hepatic tissue. Twelve patients were recruited. All patients satisfied the inclusion criteria except one who did not receive neoadjuvant chemotherapy. Eleven children underwent surgery 1 month after the last chemotherapy cycle. All are alive disease-free. Histological examination of specimen revealed only mild changes such as diffuse swelling of hepatocytes and focal, mild portal inflammation. Severe hepatic changes such as steatosis, necrosis, or fibrosis were not identified. CALI-related morphological changes were not found in our patients. The absence of the CALI could be attributed to the younger age of patients (possible different response to stress) and/or to the different chemotherapy schedules compared to those in use for adults patients.

Brain Metastases from Breast Cancer Histologically Exhibit Solid Growth Pattern with at Least Focal Comedonecrosis: A Histopathologic Study on a Monocentric Series of 30 Cases.

Since there are no morphological clues capable of making a pathologist suspect a possible mammary origin of a metastatic lesion without adequate clinical information, the histologic diagnosis of brain metastasis from BC is still based on the immunohistochemical expression of mammary gland markers such as GATA-3, ERs, PgRs and HER-2. The present retrospective study aimed to select purely morphological features capable of suggesting the mammary origin of a metastatic carcinoma in the brain. The following histological features were collected from a series of 30 cases of brain metastases from breast cancer: (i) a solid growth pattern; (ii) the presence of comedonecrosis; and (iii) glandular differentiation. Our results showed that most cases histologically exhibited a solid growth pattern with at least focal comedonecrosis, producing an overall morphology closely reminiscent of mammary high-grade ductal carcinoma in situ. Although the above-mentioned morphological parameters are not strictly specific to a mammary origin, they may have an important diagnostic utility for leading pathologists to suspect a possible breast primary tumor and to include GATA-3, ERs, PgRs and HER-2 in the immunohistochemical panel.

Tumor Infiltrating Lymphocytes (TILS) and PD-L1 Expression in Breast Cancer: A Review of Current Evidence and Prognostic Implications from Pathologist's Perspective.

With the rise of novel immunotherapies able to stimulate the antitumor immune response, increasing literature concerning the immunogenicity of breast cancer has been published in recent years. Numerous clinical studies have been conducted in order to identify novel biomarkers that could reflect the immunogenicity of BC and predict response to immunotherapy. In this regard, TILs have emerged as an important immunological biomarker related to the antitumor immune response in BC. TILs are more frequently observed in triple-negative breast cancer and HER2+ subtypes, where increased TIL levels have been linked to a better response to neoadjuvant chemotherapy and improved survival. PD-L1 is a type 1 transmembrane protein ligand expressed on T lymphocytes, B lymphocytes, and antigen-presenting cells and is considered a key inhibitory checkpoint involved in cancer immune regulation. PD-L1 immunohistochemical expression in breast cancer is observed in about 10-30% of cases and is extremely variable based on tumor stage and molecular subtypes. Briefly, TNBC shows the highest percentage of PD-L1 positivity, followed by HER2+ tumors. On the other hand, PD-L1 is rarely expressed (0-10% of cases) in hormone-receptor-positive BC. The prognostic role of PD-L1 expression in BC is still controversial since different immunohistochemistry (IHC) clones, cut-off points, and scoring systems have been utilized across published studies. In the present paper, an extensive review of the current knowledge of the immune landscape of BC is provided. TILS and PD-L1 expression across different BC subtypes are discussed, providing a guide for their pathological assessment and reporting.

Practical Approach to the Diagnosis of the Vulvo-Vaginal Stromal Tumors: An Overview.

BACKGROUND: The category of the "stromal tumors of the lower female genital tract" encompasses a wide spectrum of lesions with variable heterogeneity, which can be nosologically classified on the basis of their morphologic and immunohistochemical profiles as deep (aggressive) angiomyxoma (DAM), cellular angiofibroma (CAF), angiomyofibroblastoma (AMFB) or myofibroblastoma (MFB). Despite the differential diagnosis between these entities being usually straightforward, their increasingly recognized unusual morphological variants, along with the overlapping morphological and immunohistochemical features among these tumours, may raise serious differential diagnostic problems. METHODS AND RESULTS: The data presented in the present paper have been retrieved from the entire published literature on the PubMed website about DAM, CAF, AFMB and MFB from 1984 to 2021. The selected articles are mainly represented by small-series, and, more rarely, single-case reports with unusual clinicopathologic features. The present review focuses on the diagnostic clues of the stromal tumours of the lower female genital tract to achieve a correct classification. The main clinicopathologic features of each single entity, emphasizing their differential diagnostic clues, are discussed and summarized in tables. Representative illustrations, including the unusual morphological variants, of each single tumour are also provided. CONCLUSION: Awareness by pathologists of the wide morphological and immunohistochemical spectrum exhibited by these tumours is crucial to achieve correct diagnoses and to avoid confusion with reactive conditions or other benign or malignant entities.

Practical Approach to Histological Diagnosis of Peripheral Nerve Sheath Tumors: An Update.

Peripheral nerve sheath tumors encompass a wide spectrum of lesions with different biological behavior, including both benign and malignant neoplasms as well as the recent diagnostic category, i.e., "atypical neurofibromatous neoplasm with uncertain biologic potential" to be used only for NF1 patients. Neurofibromas and schwannomas are benign Schwann-cell-derived peripheral nerve sheath tumors arising as isolated lesions or within the context of classical neurofibromatosis or schwannomatoses. Multiple tumors are a hallmark of neurofibromatosis type 1(NF1) and related forms, NF2-related-schwannomatosis (formerly NF2) or SMARCB1/LZTR1-related schwannomatoses. Perineuriomas are benign, mostly sporadic, peripheral nerve sheath tumors that show morphological, immunohistochemical, and ultrastructural features reminiscent of perineurial differentiation. Hybrid tumors exist, with the most common lesions represented by a variable mixture of neurofibromas, schwannomas, and perineuriomas. Conversely, malignant peripheral nerve sheath tumors are soft tissue sarcomas that may arise from a peripheral nerve or a pre-existing neurofibroma, and in about 50% of cases, these tumors are associated with NF1. The present review emphasizes the main clinicopathologic features of each pathological entity, focusing on the diagnostic clues and unusual morphological variants.

Immunohistochemical evaluation of autotaxin and lubricin in mild osteoarthritic rat model performing moderate physical activity.

Levels of the enzyme autotaxin (ATX) are elevated in synovial fluid and plasma of osteoarthritic patients, correlating positively with radiographic and symptomatic severity of the disease. Therefore, ATX is studied as potential marker for the progression of osteoarthritis (OA), whereas the chondrocyte-secreted glycoprotein Lubricin has chondroprotective properties. The aim of this study was to evaluate the expression of ATX and Lubricin in healthy and mild OA rat articular cartilage of femur, tibia and patella, and to analyse the effect of a protocol of moderate physical activity on their expressions. Mild OA resulted from anterior cruciate ligament transection and rats exercised on a treadmill for 12 weeks. Computerized staining intensity of immunostaining was used to evaluate ATX and Lubricin expressions. Higher expressions of ATX were found in femur and tibia of OA rats, suggesting that this molecule could participate in the progression of the disease, although not involved in the patella. In the femur, physical activity performed by OA rats was able to lower ATX expression, encouraging the evidence that joint movement is beneficial for the cartilage, although no significant differences in Lubricin expression were detected in femur, tibia and patella. This evidence might shade some light about the role of ATX, Lubricin and physical exercise in OA progression.

Molecular Analysis of Luminal Androgen Receptor Reveals Activated Pathways and Potential Therapeutic Targets in Breast Cancer.

BACKGROUND/AIM: Triple-negative breast cancers represent 15% of all mammary malignancies and encompass several entities with different genomic characteristics. Among these, luminal androgen receptor (LAR) tumors express the androgen receptor (AR) and are characterized by a genomic profile which resembles luminal breast cancers. Moreover, LAR malignancies are usually enriched in PIK3CA, KMTC, CDH, NF1, and AKT1 alterations. Still, molecular features, clinical behavior and prognosis of this variant remain controversial, while identification of effective treatments represents an unmet medical need. Additionally, the predictive role of the AR is unclear. MATERIALS AND METHODS: We performed an extensive next generation sequencing analysis using a commercially available panel in a cohort of patients with LAR breast cancer followed at two local Institutions. We next employed bioinformatic tools to identify signaling pathways involved in LAR pathogenesis and looked for potentially targetable alterations. RESULTS: Eight patients were included in the study. In our cohort we found 26 known genetic alterations (KGAs) in 15 genes and 64 variants of unknown significance (VUS) in 59 genes. The most frequent KGAs were single nucleotide variants in PIK3CA, HER2, PTEN and TP53. Among VUS, CBFB, EP300, GRP124, MAP3K1, RANBP2 and TSC2 represented recurrently altered genes. We identified five signaling pathways (MAPK, PI3K/AKT, TP53, apoptosis and angiogenesis) involved in the pathogenesis of LAR breast cancer. Several alterations, including those in PIK3CA, ERBB2 and PI3K/AKT/mTOR signaling, were potentially targetable. CONCLUSION: Our findings confirm a role for PI3K/AKT/mTOR signaling in the pathogenesis of LAR breast cancers and indicate that targeting this pathway, along with ERBB2 mutations, may represent an additional therapeutic strategy which deserves further exploration in larger studies.

Benign myofibroblastic/epithelial lesions of the breast with minimally infiltrative margins.

A minority of mixed fibro-epithelial lesions of the breast lacks both fibroadenoma and phyllodes architectural patterns and have been previously labeled with different terms, including "hamartomas", "myoid/muscular hamartomas", "benign fibroadenomatous lesions" or "stromo-epithelial lesions of the breast". This study emphasizes the clinico-pathologic features of 5 cases of mammary benign fibro(stromo)-epithelial lesions sharing as a common morphologic theme the presence of minimally infiltrative margins due to the overgrowth of the stromal component into the surrounding fibro-fatty tissue. Notably the radiological features were suspicious for malignancy in 3 out of 5 cases. The following histologic features were seen in all cases: i) an epithelial component of benign glandular structures exhibiting the morphological spectrum of fibro-cystic disease; ii) a stromal component of bland-looking spindle cell myofibroblasts (vimentin + and α-smooth muscle actin +) set in a variably fibro-myxoid stroma. The present paper contributes to widen the morphological spectrum of the benign fibro-epithelial lesions of the breast, emphasizing the possibility that some cases, exhibiting a predominant myofibroblastic stromal component and minimally infiltrative margins, may be confused with other primary spindle cell mimickers of the breast. Accordingly, we propose the descriptive term "benign myofibroblastic/epithelial lesions of the breast with minimally infiltrative margins" for these previously underrecognized lesions.

Comparison of three biopsy forceps for hysteroscopic endometrial biopsy in postmenopausal patients (HYGREB-1): A multicenter, single-blind randomized clinical trial.

OBJECTIVE: To compare three types of biopsy forceps for hysteroscopic endometrial biopsy in postmenopausal women. METHODS: Postmenopausal women undergoing operative hysteroscopy with endometrial biopsy for abnormal uterine bleeding or endometrial thickness (≥5 mm) were included. Operative hysteroscopy with endometrial biopsy was performed by hysteroscopic forceps. Women were randomized (1:1:1 ratio) in three groups and allocated to undergo endometrial biopsy by hysteroscopy using spoon, alligator, or snake forceps. RESULTS: Seventy-five women were included in the study, 25 in each group. The duration of the biopsy was comparable between the three groups (P = 0.334) with a median of 180 seconds (range 20-480 seconds). No differences were observed about the number of attempts (P = 0.602), the use of another instrument (P = 0.276), and the biopsy appropriateness (P = 0.592). The spoon forceps group reported higher levels of pain compared to the alligator and snake forceps groups (P < 0.001). The spoon forceps received significantly lower scores by the operator compared to the alligator and snake forceps (P < 0.001). The alligator and snake forceps reported wider biopsy than the spoon forceps (P < 0.001). CONCLUSION: Snake and alligator hysteroscopic forceps may be considered the first choice to perform an endometrial biopsy in postmenopausal women. ClinicalTrials.gov: NCT03427957.

WT1 and Cyclin D1 Immunohistochemistry: A Useful Adjunct for Diagnosis of Pediatric Small Round Blue Cell Tumors on Small Biopsies.

Pediatric small round blue cell tumors (SRBCTs) are a heterogeneous group of neoplasms with overlapping morphological appearance. Accordingly, their diagnosis is one of the most difficult in the field of surgical pathology. The most common tumors include rhabdomyosarcoma, Ewing's sarcoma, neuroblastoma, lymphoblastic lymphoma and Wilms' tumor (the blastemal component). Over time their diagnosis has become more difficult due to the increasing use of small biopsies. However, the advent of immunohistochemistry has improved the quality of diagnosis in most cases by the application of an adequate panel of immunomarkers. Recently, WT1 and Cyclin D1 have been shown to be useful in the differential diagnosis of SRBCTs on surgically-resected specimens, showing a diffuse cytoplasmic positivity of the former in all RMSs and a diffuse nuclear staining of the latter in both EWS and NB. The aim of the present study was to investigate the expression of WT1 and Cyclin D1 on small biopsies from a series of 105 pediatric SRBCTs to evaluate their diagnostic utility. Both immunomarkers were differentially expressed, with a diffuse and strong cytoplasmic staining for WT1 limited to all cases of RMS, and a diffuse nuclear staining for cyclin D1 restricted to all cases of EWS and NB. Notably, the expression of WT1 and cyclin D1 was also retained in those cases in which the conventional tumor markers (myogenin, desmin and MyoD1 for RMS; CD99 for EWS; NB84 for NB) were focally expressed or more rarely absent. The present study shows that WT1 and Cyclin D1 are helpful immunomarkers exploitable in the differential diagnosis of pediatric SRBCTs on small biopsies, suggesting their applicability in routine practice.

Early Gastrointestinal Progression to Immunotherapy in Lung Cancer: A Report of Two Cases.

Intestinal and pancreatic metastases are rare and often challenging to recognize and manage. Lung cancer patients with enteric involvement usually display poor outcomes. Hyperprogression to immunotherapy represents a concern, even though there is currently no agreement on its exact definition. Gastrointestinal hyperprogression to immune checkpoint inhibitors has not been described so far. In these cases, distinguishing disease-related symptoms from immune-related adverse events may represent a diagnostic conundrum. Here, we report two cases of non-small-cell lung cancer experiencing a rapid pancreatic and colic progression to immunotherapy, respectively. While further investigations to identify biomarkers associated with hyperprogression are warranted, clinicians should be aware of the potential unusual clinical presentations of this phenomenon.

Solitary cutaneous histiocytosis with granular cell changes: a morphological variant of reticulohistiocytoma?

We first report a case of granular cell histiocytosis occurring as a solitary polypoid lesion of the nipple in a 15-year-old girl. Histologically, the lesion was composed of a dermal population of medium- to large-sized, short spindle- to round- to epithelioid-shaped cells with eosinophilic cytoplasm containing numerous and small diastase-resistant periodic acid-Schiff (PAS) positive granules. No associated inflammatory cells were observed. Immunohistochemical studies, revealing immunoreactivity exclusively to vimentin and CD68, were consistent with their histiocytic profile. Based on clinical, morphological and immunohistochemical features, the diagnosis of 'solitary cutaneous histiocytosis with granular cell changes' was proposed. The absence of an inflammatory cell component, such as lymphocytes and leucocytes, along with no history of a previous trauma or medical treatment, suggest that the present lesion could fit into the morphological spectrum of the so-called solitary epithelioid histiocytoma, also known as reticulohistiocytoma. Alternatively, the possibility of a histiocytic reaction to unknown stimuli cannot be completely ruled out. Nevertheless, awareness of solitary cutaneous histiocytosis with granular cell changes is useful to avoid confusion with other dermal tumors, especially 'granular cell tumor' and 'dermal non-neural granular cell tumor'.

Ductal Carcinoma In Situ of the Breast: An Update with Emphasis on Radiological and Morphological Features as Predictive Prognostic Factors.

Ductal carcinoma in situ (DCIS) shows overlapping epidemiology with invasive ductal carcinoma of the breast, sharing similar risk factorssuch as age, mammographic density, family history, and hormonal therapy as well as genetic factors such as BRCA1/BRCA2, histotypes, and molecular subtypes such as luminal A and B, HER2 enriched, and basal-type, thus suggesting its potential precursor role. A small percentage of patients with a history of DCIS die without a documented intermediate diagnosis of invasive breast carcinoma (IBC). The increased risk of death is usually associated with ipsilateral recurrence such as IBC. The slightly variable incidence of DCIS in different countries is mainly due to a different diffusion of mammographic screening and variability of the risk factors. The majority of DCIS lesions are not palpable lesions, which can be only radiologically detected because of the association with microcalcifications. Mammography is a highly sensitive diagnostic procedure for detecting DCIS with microcalcifications, while magnetic resonance imaging (MRI) is considered more sensitive to detect DCIS without calcifications and/or multifocal lesions. The aim of the present overview was to focus on the clinical, radiological, and pathological features of DCIS of the breast, with an emphasis on the practical diagnostic approach, predictive prognostic factors, and therapeutic options.

The prognostic impact of neoadjuvant chemoradiotherapy on lymph node sampling in patients with locally advanced rectal cancer.

According to the American Joint Committee on Cancer, at least 12 lymph nodes are required to accurately stage locally advanced rectal cancer (LARC). Neoadjuvant chemoradiation therapy (NACRT) reduces the number of lymph nodes retrieved during surgery. In this study, we evaluated the effect of NACRT on lymph node retrieval and prognosis in patients with LARC. We performed an observational study of 142 patients with LARC. Although our analysis was retrospective, data were collected prospectively. Half the patients were treated with NACRT and total mesorectal excision (TME) and the other half underwent TME only. The number of lymph nodes retrieved and the number of metastatic lymph nodes were significantly reduced in the NACRT group (P > 0.001). In the univariate and multivariate analyses, only NACRT and patient age were significantly associated with reduced lymph node retrieval. The number of metastatic lymph nodes and the lymph node ratio (LNR) both had a significant effect on prognosis when the patient population was examined as a whole (P = 0.003 and P = 0.001, respectively). However, the LNR was the only significant, independent prognostic factor in both treatment groups (P = 0.007 for the NACRT group; P = 0.04 for the no-NACRT group). NACRT improves patient prognosis only when the number of metastatic lymph nodes is reduced. The number of metastatic lymph nodes and the LNR are important prognostic factors. Lymph node retrieval remains an indispensable tool for staging and prognostic assessment of patients with rectal carcinoma treated with NACRT.