Search

Deep models for cell detection have demonstrated utility in bone marrow cytology, showing impressive results in terms of accuracy and computational efficiency. However, these models have yet to be implemented in the clinical diagnostic workflow. Additionally, the metrics used to evaluate cell detection models are not necessarily aligned with clinical goals and targets. In order to address these issues, we introduce cell projection plots (CPPs), which are novel, automatically generated visual summaries of bone marrow aspirate specimens. CPPs provide a compact summary of bone marrow aspirate cytology, and encompass relevant biological patterns such as neutrophil maturation. To gauge clinical relevance, CPPs were shown to three hematopathologists, who decided whether shown diagnostic synopses matched with generated CPPs. Pathologists were able to match CPPs to the correct synopsis with 85% accuracy. Our finding suggests CPPs can compactly represent clinically relevant information from bone marrow aspirate specimens, and may be used to efficiently summarize bone marrow cytology to pathologists. CPP could be a step toward human-centered implementation of artificial intelligence (AI) in hematopathology, and a basis for a diagnostic support tool for digital pathology workflows.

Recent advances in interventional radiology have resulted in the utilization of small lymph node biopsies, including fine-needle aspiration (FNA) and core needle biopsy (CNB) as an initial diagnostic tool in hematopathology. A major challenge to the utilization of FNA and CNB is the limited-to-scant tissue often available. We propose delegation of the task of handling biopsy specimens to the laboratory staff by the biopsy operators, in order to optimize the utilization of the specimen. Furthermore, in order to effectively diagnose hematolymphoid neoplasms a variety of ancillary tests including immunohistochemistry, flow cytometry, molecular analysis, florescence in situ hybridization (FISH) are necessary. We propose morphological evaluation coupled with careful utilization of ancillary studies along with clinical correlation to approach the correct diagnosis. Our morphological assessment considers the types of proliferating cell population: mainly small cells, sheets of large cells, or scattered large cells among small cells. This is followed by employment of the corresponding immunopanel to assess the differential diagnosis in each of the three categories. We also elaborate on the importance for pathologists to become proficient in understanding the limitations of small tissue biopsies as well as the differences in interpretation, and wording their reports to help clinicians and direct them to further investigate and/or to re-biopsy when necessary.

Patients with advanced low-grade serous carcinoma (LGSC) have poor long-term survival rates. As a rare histotype, there are uncertainties regarding the use of current therapies. Thus, we studied practice patterns and treatment outcomes as part of a national initiative to better understand and improve the care of women with advanced LGSC.This retrospective cohort study was conducted in 5 Canadian referral institutions from 2000 to 2016. Data collection and pathology reporting were standardized. Outcome measures included overall survival (OS), progression-free survival (PFS), progression-free intervals (PFI), and time to next treatment (TTNT). Cox regression analysis was used to evaluate the effects of clinical and pathologic factors on outcomes and prognosis.There were 134 patients (stage II-IV) with a median follow-up of 32.4 months (range 1.6-228). Four primary treatments were compared across institutions: 1) surgery followed by chemotherapy (56%), 2) neoadjuvant chemotherapy (NACT) followed by surgery (27%), 3) surgery alone (9%), and 4) surgery followed by anti-hormone therapy (4%). Primary platinum/paclitaxel chemotherapy was used in 81%. Patients treated with NACT had worse PFS. Multivariable Cox regression analysis identified lesser residual disease, younger age, and primary peritoneal origin as variables significantly associated with better OS/PFS (p 0.03). One institution had significantly better PFS than the others (p = 0.025), but this finding could be related to a higher frequency of primary peritoneal LGSC. PFI and TTNT intervals in patients with relapsed disease were not significantly different after the first relapse irrespective of treatment type.There are notable differences in practice patterns across Canada. This underscores the need for ongoing strategies to measure, evaluate and achieve optimal patient outcomes for women with advanced LGSC.

Lymphomas associated with breast implants are mostly of the T-cell type. They are predominantly anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALK-negative ALCL) characterized by CD30 positivity universally. Whilst the majority of primary breast lymphomas occurring in the absence of breast implants are of B-cell origin, there are few cases of implant-associated B-cell lymphomas reported to date in the literature, a subset of which are diffuse large B-cell lymphoma (DLBCL). Given the rarity of this entity, we describe two cases of breast implant-associated DLBCL. Both patients developed Epstein-Barr Virus (EBV)-positive large cell lymphoma of B-cell origin confined to the implant capsule with no evidence of systemic lymphoma. Considering the association with EBV, the activated B-cell phenotype and the presumed chronic inflammatory environment associated with the implant capsule, these might represent forms of DLBCL associated with chronic inflammation (DLBCL-CI) or fibrin-associated DLBCL (FA-DLBCL). Treatment included implant removal with total capsulectomy, and for one of the cases adjuvant systemic chemotherapy. Recognizing this rare type of breast implant-associated B-cell lymphoma could improve our understanding of this entity and hence develop appropriate management strategies.

Background Bone marrow cytology is required to make a hematological diagnosis, influencing critical clinical decision points in hematology. However, bone marrow cytology is tedious, limited to experienced reference centers and associated with inter-observer variability. This may lead to a delayed or incorrect diagnosis, leaving an unmet need for innovative supporting technologies. Methods We develop an end-to-end deep learning-based system for automated bone marrow cytology. Starting with a bone marrow aspirate digital whole slide image, our system rapidly and automatically detects suitable regions for cytology, and subsequently identifies and classifies all bone marrow cells in each region. This collective cytomorphological information is captured in a representation called Histogram of Cell Types (HCT) quantifying bone marrow cell class probability distribution and acting as a cytological patient fingerprint. Results Our system achieves high accuracy in region detection (0.97 accuracy and 0.99 ROC AUC), and cell detection and cell classification (0.75 mean average precision, 0.78 average F1-score, Log-average miss rate of 0.31). Conclusions HCT has potential to eventually support more efficient and accurate diagnosis in hematology, supporting AI-enabled computational pathology.

Immunohistochemistry (IHC) for mismatch repair (MMR) proteins is an established test to identify Lynch syndrome (LS) in patients with colorectal cancer and is being increasingly used to identify LS in women with endometrial and/or nonserous ovarian cancer (OC). We assessed interobserver agreement in the interpretation of MMR-IHC on endometrial and ovarian carcinomas. The study consisted of 73 consecutive endometrial cancers (n=48) and nonserous, nonmucinous epithelial OCs (n=25). Six pathologists from 2 cancer centers, one with and the other without, previous experience in interpreting MMR-IHC, evaluated MLH1, MSH2, MSH6, and PMS2 stains. Before the study, an experienced pathologist led a review of 9 teaching cases. A decision tool was developed as a guide in MMR-IHC interpretation. Staining was interpreted as intact, deficient, or equivocal for each protein. Interobserver agreement for the patient MMR status was categorized as "almost perfect" with κ=0.919 (95% CI, 0.863-0.976). All observers were in agreement in 66 (92%) tumors. Four of the less experienced pathologists had at least 1 discrepant interpretation. There were 6 discordant cases: 3 MMR-deficient cases and 2 MMR-intact cases by majority opinion were called equivocal by at least 1 observer, and 1 MMR-deficient case by majority opinion was interpreted as MMR intact by 1 pathologist. Only the latter case (1/73 patients, 1.4%) had an unequivocal disagreement that could affect patient management. Issues associated with discordant interpretation included heterogeneous staining, intratumoral lymphocytes, regional reduced internal control tissue staining, and scattered absent/weak staining adjacent to tumor cells with strong nuclear staining.

Pathology synopses consist of semi-structured or unstructured text summarizing visual information by observing human tissue. Experts write and interpret these synopses with high domain-specific knowledge to extract tissue semantics and formulate a diagnosis in the context of ancillary testing and clinical information. The limited number of specialists available to interpret pathology synopses restricts the utility of the inherent information. Deep learning offers a tool for information extraction and automatic feature generation from complex datasets. Using an active learning approach, we developed a set of semantic labels for bone marrow aspirate pathology synopses. We then trained a transformer-based deep-learning model to map these synopses to one or more semantic labels, and extracted learned embeddings (i.e., meaningful attributes) from the model’s hidden layer. Here we demonstrate that with a small amount of training data, a transformer-based natural language model can extract embeddings from pathology synopses that capture diagnostically relevant information. On average, these embeddings can be used to generate semantic labels mapping patients to probable diagnostic groups with a micro-average F1 score of 0.779 Â ± 0.025. We provide a generalizable deep learning model and approach to unlock the semantic information inherent in pathology synopses toward improved diagnostics, biodiscovery and AI-assisted computational pathology. Pathology synopses are short texts describing microscopic features of human tissue. Medical experts use their knowledge to understand these synopses and formulate a diagnosis in the context of other clinical information. However, this takes time and there are a limited number of specialists available to interpret pathology synopses. A type of artificial intelligence (AI) called deep learning provides a possible means of extracting information from unstructured or semi-structured data such as pathology synopses. Here we use deep learning to extract diagnostically relevant textual information from pathology synopses. We show our approach can then map this textual information to one or more diagnostic keywords. We provide a generally applicable and scalable method to unlock the knowledge in pathology synopses as a step toward exploiting computer-aided pathology in the clinic. Mu et al. utilize a deep learning natural language processing model as part of an active learning approach to extract diagnostically relevant semantic information from bone marrow pathology synopses. Their findings demonstrate the potential for artificial intelligence in assisting clinicians in assessing, cataloging and triaging medical text datasets such as pathology synopses.

Intravascular large B cell lymphoma (IVLBCL) is a rare type of extranodal diffuse large B-cell lymphoma. Patients typically present with nonspecific findings, particularly bizarre neurologic symptoms, fever, and skin lesions. IVLBCL with primary lung presentation is very rare and difficult to diagnose. The authors report a case of a 75-year-old male who presented with neurological symptoms and showed diffuse pulmonary ground glass opacities on computed tomography scan (CT scan). Surgical lung biopsy was performed. Light microscopic examination of the specimen showed diffuse alveolar septal widening caused by neoplastic lymphocytes, which were positive for CD20. These atypical lymphoid cells also demonstrated angiotropism/angioinvasion of the medium sized pulmonary vessels. The patient was diagnosed with IVLBCL and underwent chemotherapy. The patient is still alive 12 months after diagnosis.

Female adnexal tumor of probable wolffian origin (FATWO) is a tumor of low malignant potential that arises predominantly in the broad ligament, mesosalpinx, and ovarian hilus. The rarity of FATWO increases its susceptibility to misdiagnosis as other tumors, especially when it occurs at an unusual site. We report a 29-year-old woman with a 7.2 cm left paravaginal FATWO that invaded into the vaginal lumen. The initial biopsy demonstrated features suggestive of vaginal spindle cell epithelioma, but with increased Ki67 proliferation index. Pathologists should be aware that the common sieve-like architecture of FATWO may not be apparent on small biopsies, which by sampling error may demonstrate predominantly the less common spindle cell architecture. Awareness of FATWO in the differential diagnosis of paravaginal tumors may help to avoid misinterpretation as vaginal spindle cell epithelioma, a previously unappreciated pitfall in the diagnosis of FATWO.

The ovary shows an innate potential for markedly variable histogenesis, including squamous differentiation. Although not uncommon, squamous differentiation in ovarian lesions can be present in several diagnostic contexts, both benign and malignant. We present a review of the literature pertaining to squamous lesions of the ovary. In particular, we summarize the relevant clinical features, workup, gross findings and histopathologic features, differential diagnosis, treatment, and prognostic features of both the common and rare squamous entities found in the ovary.

Objective. Morphologically,β-HCG secreting somatic carcinoma can be difficult to distinguish from epithelioid trophoblastic tumors (ETT). However, their distinction is critical due to their potentially differing prognoses and choice of chemotherapy. Presence of biparental alleles in ETT can be identified with molecular testing. We describe a patient who presented with metastatic carcinoma and elevated serumβ-HCG and contrast this to an ETT in another patient.Data and Results. A 32-year-old female with recent possible miscarriage presented with pulmonary emboli and was found to have an increased serumβ-HCG, a retroduodenal mass, and multiple nodules in her lungs, liver, and para-aortic lymph nodes. Biopsy showed aβ-HCG and p63 positive epithelioid neoplasm with otherwise noncontributory immunohistochemistry. Molecular testing for biparental alleles in repeated length polymorphisms was negative, consistent with somatic origin. The second patient was a 35-year-old pregnant female with increased serumβ-HCG and a uterine epithelioid tumor positive forβ-HCG. Clinical and pathologic findings were characteristic of ETT and molecular testing was not required. These 2 cases illustrate thatβ-HCG secreting tumors of different etiologies may have similar appearances, and when clinical and/or IHC findings are inconclusive, molecular testing may be useful.

BACKGROUND Gliomatosis of the brain or spinal cord is an infiltrating glial neoplasm that shows widespread invasion of the central nervous system with relative sparing of the underlying cytoarchitecture. Acceptance of the idea that the condition represents a distinct entity remains controversial in the absence of conclusive pathogenetic data. The clinico-pathological problems and difficulties in the ante-mortem diagnosis as well as the clinical and pathological similarities to infective lesions are evaluated. METHODS AND RESULTS Three cases of cerebral and spinal gliomatosis are presented that clinically mimicked infective lesions and were diagnosed and treated as such. The correct diagnosis in each case was only made at post-mortem examination. The ante-mortem diagnosis of this rare tumor remains difficult owing to poor correlation of clinical, neuroradiological, and neuropathological findings. CONCLUSION Gliomatosis of the brain and spinal cord may simulate infective lesions owing to difficulty in ante-mortem diagnosis because of vagueness of physical, radiological, and pathological findings. It is a diagnostic pitfall particularly in our setting where there is a high incidence of HIV/AIDS and patients often present with opportunistic infections such as mycobacterial, fungal, and/or viral infections, which show an atypical clinical picture and radiological findings. Multifocal neurologic deficit with noncontrast enhancing lesions that show diffuse contiguous involvement with overall preservation of the spinal or cerebral architecture and do not respond to infective treatment could suggest a diagnosis of gliomatosis cerebri.

Aim: To investigate the prevalence of human papillomavirus in transitional cell carcinoma of the urinary bladder in South Africa. Methods: Ninety-one archival samples of bladder transitional cell carcinoma were subjected to polymerase chain reaction (PCR) and non-isotopic in situ hybridisation (NISH) for the detection of human papillomavirus 6, 11, 16, 18, 31, and 33 genotypes. Results: HPV was detected in only one case with PCR. HPV was not detected in any of the cases subjected to the NISH system. Conclusion: This study shows that although HPV has been shown to be associated with uterine cervical and esophageal squamous cell carcinomas in South Africa, this virus is not present in the transitional cell carcinoma of the urinary bladder in this geographical location. It is suggested that other factors, including nitrosamine exposure, p53 mutation, and additional unknown chromosomal events, may play a role in the carcinogenesis of this neoplasm in the bladder.

Lipomembranous panniculitis is a peculiar type of fat necrosis and has been reported with several clinical conditions, commonly with peripheral vascular diseases. We are reporting a case of a 68-year-old woman with known liver cirrhosis and diabetes who presented with painful erythematous swelling of the right leg. Histological examination revealed microcystic changes within the subcutaneous fat. The microcysts were lined by acellular, eosinophilic membrane forming pseudopapillae and stained with periodic acid-Schiff stain. This histological feature is diagnostic of lipomembranous panniculitis. The pathologists should be aware of this entity because it aids the clinicians in investigating for associated clinical disorders.

Esophageal squamous cell carcinoma (ESCC) demonstrates wide regional variation in incidence and causal associations. Human papillomavirus (HPV) has been implicated in ESCC, particularly the sub-types 16 and 18. Transforming proteins E6 and E7 from these high risk sub-types, interact with p53 protein and Rb protein respectively, leading to loss of function of these tumor suppressor gene products. These interactions further lead to inactivation of the growth suppressive effects of the p53 and Rb proteins, resulting in abnormal proliferative states. p53 protein expression has been found in both HPV-positive and -negative tumors, indicating that HPV and p53 protein expression are not mutually exclusive and can occur together in the same tumor. It has been observed that HPV plays a more significant role in esophageal carcinogenesis in geographic areas with a high prevalence of the disease. A variation in the association between HPV and ESCC worldwide may be due to environmental and geographic factors, or to genetic susceptibility to esophageal HPV infections. Variations in the sensitivity of techniques used in the detection of the virus and in the methodology for processing the tumor tissues, may also be responsible for global differences. Esophageal carcinogenesis is a complex multistep process with a multifactorial etiology. Infection with oncogenic HPV types may be an integral part in a multistep process that leads to ESCC.

A 63-year-old woman presented with postmenopausal bleeding. The initial curettage material was reported as "undifferentiated malignant tumor." A total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed with pelvic lymph node dissection and omental biopsy, which showed an intravascular large B-cell lymphoma in the lumina of small blood vessels of the uterus, left tube, and right ovary. This is the first reported case of an intravascular lymphoma of the uterus.

Invasive squamous cell carcinoma of the vulva with ≤1 mm stromal invasion is classified as stage 1A. Cancer staging systems state that the depth of invasion should be measured from the epithelial-stromal junction of the adjacent most superficial dermal papilla to the deepest point of the invasive tumor. Measurement of the depth of invasion guides patient management. Even though this measurement is critical, no studies have reported the reliability among pathologists for determining the cutoff point of ≤1 mm stromal invasion in vulvar cancer. We assessed agreement among pathologists for determining whether a vulvar tumor is invasive, for the depth of invasion, and for tumor thickness. Forty-five cases of vulvar squamous cell carcinoma with a depth of invasion of ≤5 mm were chosen. Eleven gynecologic pathologists independently reviewed the slides and, for a subset of cases, pictorially recorded measurements on photographs. The number of cases that were reported as invasive by the 11 pathologists ranged from 21 to 44. The number of cases that were reported as showing a depth of invasion of ≤1 mm ranged from 7 to 27. Eight pathologists provided measurements for all lesions reported as invasive, the remaining 3 pathologists stated that they were unable to measure 2, 7, and 16 lesions, respectively. Mean κ for diagnosing vulvar carcinoma as invasive was 0.24 and for measuring the depth of invasion and thickness was 0.51 and 0.49, respectively. There was only fair agreement in determining whether the lesion was invasive. In cases in which pathologists agreed upon the diagnosis of invasion, agreement on depth was moderate. When using the recommended cancer staging method, interpretation of the location of the most superficial dermal papilla varied among pathologists. Measuring thickness did not improve agreement. This is the first study that has assessed the reliability of the diagnosis of invasion in vulvar cancer among gynecologic pathologists, the interobserver agreement for reporting the critical 1 mm threshold of depth of stromal invasion, and the way in which the International Federation of Gynecology and Obstetrics method is used by pathologists.

Studies have suggested serous tubal intraepithelial carcinoma (STIC) of the fallopian tube to be a putative precursor to ovarian and peritoneal serous carcinoma. It has been recommended that resected fallopian tube specimens should be rigorously examined for STIC, especially in women at high risk of serous carcinoma, such as those with BRCA mutations or with a strong family history. The SEE-FIM protocol allows for the greatest surface area of the tube to be histologically assessed. There have been suggestions that multiple deeper sections should be examined if the initial hematoxylin and eosin (HE) sections are negative; however, whether this identifies more cases of STIC has not rigorously examined. We examined deeper sections from 56 cases of pelvic carcinoma in which the initial HE sections of the fallopian tubes were negative for STIC. All initial and deeper sections underwent consensus review by panel of experts in gynecologic pathology. These cases are part of a larger study in which we had examined 300 consecutive bilateral salpingectomies using the SEE-FIM protocol and a single-HE section per block and had identified 68 cases of pelvic serous carcinoma, of which 12 were associated with STIC. We calculated the sensitivity of a single-HE section to detect STIC, as compared with examination of multiple deeper sections, and reevaluated the clinicopathologic data of the parent study in light of the additional cases of STIC. In the 56 cases initially negative for STIC, 4 cases of STIC were identified after examination of multiple deeper sections of the fallopian tubes. The single-HE section SEE-FIM approach therefore detected only 75% (95% confidence interval, 51%-90%) of STIC that was present. Three of these new cases were associated with primary ovarian serous carcinoma and 1 with primary peritoneal serous carcinoma. All 3 new cases associated with ovarian carcinoma were noted in women without neoadjuvant chemotherapy. In considering the data from the parent study, we calculated a statistically significant lower incidence of STIC in women with ovarian serous carcinoma who received neoadjuvant chemotherapy as compared with those who did not (P=0.042). Our study demonstrated that additional cases of STIC can be detected if deeper sections are examined. These additional cases also highlighted a statistically significant difference in the incidence of STIC associated with ovarian serous carcinoma who received neoadjuvant chemotherapy relative to those who did not. Consideration to this should be given in future studies of the prevalence of STIC and to routine examination of salpingectomy specimens from women at high risk for pelvic serous carcinoma.

Serous tubal intraepithelial carcinoma (STIC) has been implicated in the pathogenesis of pelvic serous carcinoma. We hypothesized that, if this is the case, the frequency of STIC should be substantially lower in endometrial serous carcinomas, in nonserous gynecologic malignancies, and in benign gynecologic neoplasms than in ovarian or peritoneal serous carcinomas. From 2007 to 2009 the fallopian tubes of 342 consecutive gynecologic cases were entirely submitted for histology using the Sectioning and Extensively Examining the FIMbriated end protocol. This study included 300 of these cases (277 TAH-BSO, 23 BSO) after exclusion. The hematoxylin and eosin-stained slides from the fallopian tubes were independently reviewed by 2 gynecologic pathologists who were blinded to all other findings; disagreements were resolved by a third pathologist. Among 46 cases of ovarian malignancies, STIC was identified in 6 (18.8%) of 32 cases of serous carcinoma, but not in any other subtype. Similarly, STIC coexisted in 4 (14.3%) of 28 cases of endometrial serous carcinoma; however, no STIC was identified in any of the 74 cases of nonserous endometrial malignancies. STIC was identified in 2 (28.6%) of 7 cases of peritoneal serous carcinoma. No STIC was identified among 15 nongynecologic malignancies, 90 cases of benign conditions, and 27 cases of other conditions including 4 cases of cervical adenocarcinoma in situ and high-grade cervical intraepithelial lesions, 8 cases of endometrial atypical complex hyperplasias, and 15 cases of ovarian borderline tumors. In conclusion, the fallopian tube may be the origin of some pelvic serous carcinomas. Other possibilities that may explain the origin of pelvic high-grade serous carcinoma are discussed. Given that STIC coexisted with 14% of endometrial serous carcinomas, a more unifying theory may be that gynecologic serous carcinomas and STIC are multifocal lesions.

Owing to the striking lymphotropsism exhibited by the human immunodeficiency virus, HIV/AIDS patients demonstrate a wide breadth of both benign and malignant lymphoproliferative disorders. These disorders span the spectrum from viral lymphadenopathy to lymphocentric opportunistic infections to proliferations of uncertain and frankly malignant potential. This chapter explores a number of the many possible HIV/AIDS associated disorders from the perspective of the lymphoid system. Notably, some of these disorders are themselves AIDS defining illnesses while others are entities known to occur frequently in the HIV/AIDS population but not directly influenced by HIV infection. In most cases, HIV-associated lymphoproliferative disorders are thought to result from an aberrant host immune response in the context of chronic inflammatory stimulation rather than as a direct consequence of HIV infection.

A wide variety of noninfectious lesions have been identified in association with HIV infection. Many hematolymphoid lesions are possible in this patient group, both reactive and neoplastic. Epidemiologic data suggests that lymphoid malignancies are among the most common neoplasms in patients with HIV. We present a selective case series assembled over a 5-year period from the relatively low HIV-prevalence Hamilton Regional Laboratory Medicine Program (HRLMP), a tertiary care referral centre in Southern Ontario. This series serves to demonstrate the wide variety of lymphoid lesions that may be encountered in patients with HIV. In addition to outlining the pathologic work-up necessary in these cases, we discuss characteristics that distinguish the HIV-associated lesions from the pathobiologically similar non-HIV-associated lymphoid lesions.

Sertoliform endometrioid carcinoma (SEC) of the ovary is an uncommon variant of endometrioid carcinoma of the ovary resembling sex cord-stromal tumor of pure Sertoli and Sertoli-Leydig cell type (SLCT). This entity was first described by Young et al. (1982). Since then only a few cases of this entity have been reported (Roth et al. 1982; Guerrieri et al. 1998; Remadi et al. 1995). SEC occurs in peri- and post menopausal women with an age range of 41–89 years (mean, 60 years). Abdominal enlargement secondary to a unilateral ovarian mass is the most common presentation. Up to 10% cases show bilaterality (Young et al. 1982). The patients very rarely present with androgenic symptoms such as virulization and, to date estrogenic manifestations have been reported in one case in a series of 13 cases (Young et al. 1982). Adequate sampling, a careful search for areas of conventional endometrioid carcinoma and immunohistochemical stains is helpful in the evaluation of SEC from true ovarian sex cord stromal tumors. It is important to recognize this variant of endometrioid carcinoma and especially differentiate it from a sex cord stromal tumor. SEC as it behaves, is a low grade malignancy and displays a good prognosis if confined to the ovary.

Background Primary non-Hodgkin lymphoma (NHL) of the breast represents 0.04–0.5% of malignant lesions of the breast and accounts for 1.7–2.2% of extra-nodal NHL. Most primary cases are of B-cell phenotype and only rare cases are of T-cell phenotype. Anaplastic large cell lymphoma (ALCL) is a rare T-cell lymphoma typically seen in children and young adults with the breast being one of the least common locations. There are a total of eleven cases of primary ALCL of the breast described in the literature. Eight of these cases occurred in proximity to breast implants, four in relation to silicone breast implant and three in relation to saline filled breast implant with three out of the eight implant related cases having previous history of breast cancer treated surgically. Adjuvant postoperative chemotherapy is given in only one case. Secondary hematological malignancies after breast cancer chemotherapy have been reported in literature. However in contrast to acute myeloid leukemia (AML), the association between lymphoma and administration of chemotherapy has never been clearly demonstrated. Case Presentation In this report we present a case of primary ALCL of the breast arising in reconstruction mamoplasty capsule of saline filled breast implant after radical mastectomy for infiltrating ductal carcinoma followed by postoperative chemotherapy twelve years ago. Conclusion Primary ALK negative ALCL arising at the site of saline filled breast implant is rare. It is still unclear whether chemotherapy and breast implantation increases risk of secondary hematological malignancies significantly. However, it is important to be aware of these complications and need for careful pathologic examination of tissue removed for implant related complications to make the correct diagnosis for further patient management and treatment. It is important to be aware of this entity at this site as it can be easily misdiagnosed on histologic grounds and to exclude sarcomatoid carcinoma, malignant melanoma and pleomorphic sarcoma by an appropriate panel of immunostains to arrive at the correct diagnosis of ALCL.

Background Myxopapillary ependymomas (MPE) occur in the filum terminale of the spinal cord, but also present in extra-spinal locations such as subcutaneous tissue and brain. They are slow growing grade I gliomas. Areas of solid growth pattern with aggregates of cells with "epithelioid morphology" seen in MPE can mimic metastatic carcinoma. The presence of occasional cells with clear cytoplasm and morphology can resemble Chordoma. Diagnosis can be missed due to these morphological similarities, which could affect patient management and hence, long term survival. Case presentation We describe two cases of MPE with cytokeratin (AE1 AE3, CAM 5.2, Cytokeratin 7 and cytokeratin 20) expression. Conclusion MPE can be positive for Cytokeratins (CAM 5.2, AE1 AE3, CK7) and focally for EMA, which could be misdiagnosed as metastatic carcinoma. In cases demonstrating epithelioid and clear cell morphology, the diagnosis of MPE should be made in conjunction with histology, proper immunohistochemical profile which includes co-expression of GFAP, S-100 protein and epithelial markers, radiologic findings and site. It is important to be aware of the cytokeratin profile in MPE to avoid erroneous diagnosis with other tumour entities.

Merkel cell carcinoma is an uncommon aggressive primary cutaneous neuroendocrine carcinoma. Histologically, the differential diagnosis includes the 'small round cell' tumor group, particularly metastatic small cell carcinoma and blastic hematological malignancies involving skin/soft tissues. Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase, which is a sensitive and specific antibody for acute lymphoblastic lymphoma with a small proportion of acute myeloid leukemia showing positivity. This study investigates the expression of TdT in 20 cases with initial diagnosis of Merkel cell carcinoma. Archival blocks and slides were retrieved and reviewed and clinical information obtained from patient charts. Immunohistochemistry was performed and graded as: 0, no staining; 1+, less than 50% staining in the cells; 2+, 50% or more staining in the cells. After review, 15 cases were confirmed as Merkel cell carcinoma. Immunohistochemical positivity was as follows: 8/15 cases were positive for TdT with strong nuclear staining, morphologically resembling 'blasts', AE1AE3, CAM5.2 (15/15) (both membrane and paranuclear dot positivity), CD56 and BCL-2 (15/15), Synaptophysin (13/15), Chromogranin A (11/15), NSE (15/15), CK20 (14/15), CK7 (3/15), both CK7 and CK20 (3/15), CD117 (8/15), CD99 (2/15), CD10 (1/15). One case was negative for CK7/CK20. All 15 cases were negative for thyroid transcription factor-1, LCA, CD20, CD3 and CD34. Expanded immunohistochemical panel with positive staining for epithelial/neuroendocrine markers, CK20, negative staining for hematolymphoid markers and awareness of TdT expression and other markers that show overlap with blastic hematological malignancies avoids misinterpretation in the diagnosis of Merkel cell carcinoma. This aids in further diagnosis of Merkel cell carcinoma, avoiding the potential diagnostic pitfall with other small round cell tumors and hematological malignancies primary or metastatic to the skin.

Solitary fibrous tumors (SFTs) are well recognized in the pleura, but their occurrence at other sites has only become appreciated in recent years, as a consequence of which extrapleural examples often go unrecognized and misdiagnosed. Because of their rarity, overall experience concerning this tumor has not been significant and reports detailing radiological findings are few. We herein report an unusual case of a large retroperitoneal pelvic SFT with features of high vascularity negating successful surgical resection.

Sertoliform endometrioid carcinoma of the ovary (SEC) is an uncommon variant that bears histologic similarity to Sertoli and Sertoli-Leydig cell tumors (SLTs). Clinically, SEC affects an older population (60–70 years), while patients with SLT have an average age of 25 years and may exhibit endocrine manifestations. A number of histologic features can be used to distinguish the 2 entities, the most important ones being (1) the presence of areas with the usual pattern of endometrioid carcinoma, and (2) the presence of mucin at the apical borders of the tumor cells. Cytokeratin stains positively, while inhibin and calretinin stain negatively in SEC; the converse is true for SLTs. Based on the clinicopathologic behavior of this entity, SEC should be considered a well-differentiated carcinoma with relatively good prognosis if limited to the ovary.

Agranular CD4+/CD56+ hematodermic neoplasm is a distinct form of lymphoma with aggressive behavior and marked predilection for cutaneous involvement. Because of CD56 positivity, natural killer cells were initially suggested as the cell of origin in this tumor. In the recent World Health Organization–European Organization for Research and Treatment of Cancer classification, the term blastic natural killer cell lymphoma has been replaced with CD4+/CD56+ hematodermic neoplasm because of its derivation from a plasmacytoid dendritic cell precursor. Clinicopathologic features, immunohistochemical features, and differential diagnosis of this rare neoplasm with emphasis on the recent World Health Organization–European Organization for Research and Treatment of Cancer classification are discussed.

Systemic lupus erythematosus (SLE) is frequently accompanied by neuropsychiatric (NP) and cognitive deficits of unknown etiology. By using autoimmune MRL-lpr mice as an animal model of NP-SLE, we examine the relationship between autoimmunity, hippocampal damage, and behavioral dysfunction. Fluoro Jade B (FJB) staining and anti-ubiquitin (anti-Ub) immunocytochemistry were used to assess neuronal damage in young (asymptomatic) and aged (diseased) mice, while spontaneous alternation behavior (SAB) was used to estimate the severity of hippocampal dysfunction. The causal relationship between autoimmunity and neuropathology was tested by prolonged administration of the immunosuppressive drug cyclophosphamide (CY). In comparison to congenic MRL +/+ controls, SAB acquisition rates and performance in the “reversal” trial were impaired in diseased MRL-lpr mice, suggesting limited use of the spatial learning strategy. FJB-positive neurons and anti-Ub particles were frequent in the CA3 region. Conversely, CY treatment attenuated the SAB deficit and overall FJB staining. Similarly to mouse brain, the hippocampus from a patient who died from NP-SLE showed reduced neuronal density in the CA3 region and dentate gyrus, as well as increased FJB positivity in these regions. Gliosis and neuronal loss were observed in the gray matter, and T lymphocytes and stromal calcifications were common in the choroid plexus. Taken together, these results suggest that systemic autoimmunity induces significant hippocampal damage, which may underlie affective and cognitive deficits in NP-SLE.

Pre-brachytherapy biopsies and post-brachytherapy oesophagectomy specimens of 10 patients with early squamous cell carcinoma of the middle third of the oesophagus were examined for the expression of p53, bcl-2 and apoptosis using immunohistochemical markers. There was no expression of p53 in one patient in both pre- and post-brachytherapy specimens. In 8 patients, p53 staining was strongly positive (3+) with approximately 50% or more cells, and with diffuse and no specific pattern in the pre-brachytherapy biopsies. The tumour areas of the post-brachytherapy specimens of this group showed strong 3+ positivity with p53 (10-50% positive cell count), with the pattern being focal and peripheral in the tumour islands. The centre of the tumour islands showed necrosis and/or keratinisation. In one patient, the pre-brachytherapy biopsy showed expression of p53 while the post-brachytherapy specimen was negative. bcl-2 expression in both pre- and post-brachytherapy was equivocal and inconclusive in both the pre- and post-brachytherapy specimens. Apoptosis was negative in all the pre- and post-brachytherapy tissue sections in the presence of positive controls. Brachytherapy does not cause cell death by apoptosis but by necrosis and maturation of the cells into better differentiated cells, which is caused by OH free radical, and induction of the keratin gene respectively. It is possible that brachytherapy may cause destruction of cells containing wild-type p53, while mutant p53 in cells located at the tumour periphery escape the effect of brachytherapy. This may be responsible for the high incidence of local recurrence and distant metastasis in oesophageal cancer treated with radiotherapy. There is no effect of brachytherapy on bcl-2 expression in oesophageal cancer.

BACKGROUND. Total esophagectomy specimens from 4 patients given preoperative high dose rate intraluminal brachytherapy (HDRILBT) of 20 Gray (Gy) in 2 fractions of 10 Gy each week were reviewed for radiation changes. METHODS. In all patients, preoperative biopsy specimens showed moderate to poorly differentiated squamous cell carcinoma with minimal to negligible keratin production. The esophagectomy specimens were sampled at the resection margins, the edge of irradiated length, 1 cm from the proximal and distal edge of visible tumor, the center of the tumor, and the lymph nodes. RESULTS. Radiation change in the form of fibrosis was limited to the submucosa at the resection margins, the circular muscle layer at the edge of irradiated length, and full thickness at 1 cm from the edge of the visible tumor and the center of the tumor. Surface epithelium did not show any changes at the resection margins but did show basal cell hyperplasia at the edge of the irradiated length and ulceration at 1 cm from the edge of the visible tumor and the center of the tumor. Endarteritis obliterans was seen only 1 cm from the edge of the visible tumor and the center of the tumor. Necrosis, intense keratin formation, and giant cell reaction were observed at the center of the tumor. When compared with the preradiotherapy biopsies, the amount of keratin in the postradiotherapy specimens was extensive. HDRILBT may cause induction of the keratin gene in the irradiated cells to stimulate differentiation toward better differentiated cells. CONCLUSIONS. HDRILBT may cause the keratin gene in the irradiated cells to induce differentiation toward better differentiated cells. Preoperative high dose rate intraluminal brachytherapy may have a role in improving the prognosis of patients with early esophageal cancer treated with a combination of radiotherapy and surgery.

Synchronous composite tumors have been described but are uncommon. Moreover, simultaneous occurrence of synchronous tumors in the same tissue or organ is even less common. We report a case of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma and malignant melanoma (MM) occurring synchronously in the same lymph node. Several cases of an association between cutaneous malignancies and lymphoproliferative disorders have been reported. Some of which included CLL and MM, occurring in the same patient often CLL after MM. The risk of having CLL after MM has been reported to be increased. Various genetic and environmental etiologies have been postulated, but have as yet not been proven. To our knowledge this is the first time that synchronous occurrence of these two malignant processes in the same tissue is described. In this case it is important that the melanoma was recognized in the excised lymph node, as this finding had much more critical treatment and long term survival consequences.

Synchronous composite tumors though described are uncommon. Moreover, simultaneous occurrence of synchronous tumors involving the same tissue or organ at multiple sites is even less common. We report a case of acute lymphoblastic leukemia (ALL) and basal cell carcinoma (BCC) occurring simultaneously in multiple skin sites. Several cases showing an association between cutaneous malignancies and lymphoproliferative disorders have been reported. Some of these cases included ALL and BCC and occurred often in the pediatric population with the BCC arising as a post-ALL therapy sequela. Other rare genetic causes may be considered. To our knowledge this is the first time that the synchronous occurrence of these two malignant processes in the same tissue involving multiple sites in an elderly patient is described.