Anaplastic large cell lymphoma (ALCL) is a rare systemic T-cell neoplasm that typically involves nodal and extranodal sites and is further classified into 2 subgroups: anaplastic lymphoma kinase (ALK-) positive (ALK(+)) and ALK-negative. Leukemic presentation of ALCL is extremely rare. Most cases with leukemic presentation are the small-cell variant of ALK(+) ALCL, are positive for the t(2;5)(p23;q35) translocation, and are associated with a poor prognosis. We report a case of ALK(+) ALCL that presented with a high white blood cell count and morphologic and phenotypic features resembling T-cell prolymphocytic leukemia.
Critical value reporting is an important facet of laboratory management and represents a significant potential challenge in patient care delivery, as well as a high-value target for quality improvement initiatives in both anatomic and clinical pathology settings. A recurring problem concerns successfully contacting unavailable health care providers with unexpected and/or time-sensitive results. We report a case of an incidentally detected and unexpected finding of tumor cells in a routine hip arthroplasty, in a patient under surgical management for a variety of chronic issues including peripheral arterial disease and traumatic fall. The abnormal result proved to be the first presentation of a widely disseminated metastatic melanoma. Although multiple associated health care providers were successfully contacted with the unexpected finding and acknowledged awareness of the concern for metastatic melanoma, one provider was not successfully contacted with the pathology result, leading to frustrations among multiple parties and a slight delay in appropriate patient referral. The sequence of events presents an opportunity to review standards of care regarding urgent diagnosis reporting in anatomic pathology and assess the published literature surrounding this issue.
Abstract Timeliness of surgical pathology result reporting is a critical quality metric for patients and treating clinicians. Over the past several decades, studies have sought to define laboratory turnaround time (TAT) in the context of the surgical pathology workflow, investigate the various factors that influence TAT, and develop a framework to monitor, measure, and track TAT within and across laboratories. However, the complexity of health care delivery and health information technology creates barriers to tracking TAT that should be considered in the context of local environments. We seek to provide background and context as well as a framework for tracking TAT as a key quality metric in surgical pathology. We outline a roadmap to monitoring local TAT to maximize efficiency and customer satisfaction while reducing diagnostic error and near-miss safety events.
Quality assurance measures in the cytology laboratory help ensure accurate and consistent diagnoses. For thyroid fine-needle aspirations (FNAs), various cytologist performance metrics have been proposed to help monitor and explain cytologist practice patterns. Thoughtful implementation of metrics such as diagnostic category utilization rates, ratios of key diagnostic categories, surgical outcome data, and correlation with ancillary molecular testing results have been proposed to help minimize the use of indeterminate diagnostic categories in thyroid FNAs, such as atypia of undetermined significance. Development of laboratory dashboards coupled with periodic confidential feedback to the cytopathologist or cytotechnologist can help monitor and correct practice patterns that fall outside target norms.
Malignant peritoneal mesothelioma is an aggressive malignancy that often mimics carcinomatosis both clinically and histologically, making definitive diagnosis challenging for the general pathologist. Many of the common immunohistochemical stains used to narrow the differential diagnosis show a lack of specificity, requiring a panel approach to ensure correct categorization. We report a case of epithelioid malignant peritoneal mesothelioma with diffuse and strong Ber-EP4 positivity and review some of the most commonly encountered pitfalls associated with immunohistochemical staining.
Angiosarcoma is a rare and highly malignant neoplasm that commonly affects previously irradiated areas and areas of chronic lymphedema, classically presenting in the face and scalp. Angiosarcoma is estimated to have an incidence of .5 per 1,000,000 people in the United States, comprising fewer than 1% of all sarcomas. Epithelioid angiosarcoma is a rare, aggressive subtype that carries a poor prognosis and high mortality rate. Here, we present a case in which a lesion on the scalp was initially misdiagnosed as a malignant melanoma, but after further immunohistochemical stains and a wider excisional biopsy, a cutaneous angiosarcoma with epithelioid features simulating melanoma was revealed.
Tissue contamination, where extraneous tissue becomes embedded into the paraffin block or fixed onto the slide, is a relatively common quality issue in surgical pathology and can occur at any step between specimen collection by the clinician and slide coverslipping. We report a case of tissue contamination within a paraffin block and describe our subsequent investigation, which was successful in identifying the source of contamination.
We describe a pediatric patient with an intra-axial tumor; histopathologic examination of the resected specimen was unable to establish a precise diagnosis. While the initial targeted next-generation sequencing (NGS) panel was also nondiagnostic, genomic DNA methylation profiling indicated that the tumor was an astroblastoma, MN1-altered. A more comprehensive NGS panel was then run, which confirmed an MN1-BEND2 fusion. This case displays the limitations and pitfalls of a histological and immunohistochemical-based diagnosis in a case of an infrequently encountered pediatric brain tumor. Furthermore, it highlights the growing need for performing DNA methylation, paired with a comprehensive NGS panel, to ensure an accurate diagnosis in modern surgical neuropathology.
Abstract The morphologic overlap between low-grade spindle cell lesions can lead to diagnostic dilemmas, particularly when attempting to interpret limited material. Evaluation of such specimens frequently requires correlating with clinical and imaging findings, as well as ancillary studies. We discuss the case of a 78-year-old woman with a remote history of breast carcinoma who presented with a left base of neck nodule. While imaging findings were highly suggestive of schwannoma, fine-needle aspiration biopsy of the nodule was performed for diagnostic confirmation. The patient reported tingling and an electrical shock sensation traveling down her arm during the fine-needle aspiration procedure. Cytomorphologic findings demonstrating a low-grade spindle cell neoplasm further supported a diagnosis of schwannoma, despite early immunohistochemistry results not being supportive. A last-minute suggestion that the differential diagnosis be broadened prompted additional immunohistochemical workup and follow-up molecular testing that confirmed an alternative diagnosis of solitary fibrous tumor. This case demonstrates the importance of correlating clinical, radiologic, and pathologic findings when approaching the differential diagnosis of low-grade spindle cell lesions on fine-needle biopsy specimens. Ancillary testing including immunohistochemistry, molecular studies, or fluorescence in situ hybridization is frequently utilized to establish a definitive diagnosis.
Chronic endometritis (CE) is a controversial clinical and pathological entity. Although the presence of plasma cells (PCs) is the most frequently used diagnostic criterion for CE, the minimal diagnostic criteria remain controversial and undefined. The clinical setting of CE (asymptomatic, pelvic inflammatory disease, infertility) is an important consideration regarding the clinical significance of endometrial PCs. In the setting of infertility, specifically recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL), CE may have a negative impact on endometrial receptivity, resulting in higher rates of implantation failure. The proposed pathophysiology is that a subclinical intrauterine infection alters the local inflammatory milieu resulting in a shift of the normal inflammatory cell profiles toward responses associated with implantation failure and poorer reproductive outcomes. Cure rates following antibiotic treatment are reported to be high (up to 90%). The results of meta-analyses describing the effect of CE on reproductive outcomes are mixed. There is evidence supporting CE as a treatable factor with improved reproductive outcomes following treatment and there are also results showing no differences in reproductive outcomes. Variable diagnostic criteria for CE, inclusion criteria, and treatment regimens between studies are the main limitations, hampering the ability to compare results across studies. Results regarding the optimal diagnostic criteria in the setting of RIF and RPL are also variable, with some authors recommending a cutoff of 1 or more CD138(+) PCs per high-power field and some recommending a cutoff of 5 or more CD138(+) PCs per high-power field. There are some studies indicating CE as a negative prognostic factor in patients with RIF and RPL, which may be reversible with antibiotic treatment. The optimal diagnostic criteria for CE in this clinical setting are undefined. For the investigation of infertility patients whom clinicians intend to treat, a descriptive diagnosis (indicating the presence/number of PCs and method of identification) is a reasonable approach. Routine use of CD138 immunohistochemistry is of limited value for the diagnosis of CE.
Mesonephric-like adenocarcinomas are endometrial and ovarian neoplasms of mullerian origin with morphologic, immunophenotypic, and molecular evidence of mesonephric-type transdifferentiation, as well as considerable homology with endometrioid tumors. First described in 2016, mesonephric-like adenocarcinomas are morphologically indistinguishable from "true" mesonephric adenocarcinomas of the uterine cervix, but the latter are distinguished by (1) primary localization to the cervical wall, (2) frequent association with mesonephric remnants, and (3) in some cases, lack of mucosal involvement. Despite an overall low-grade morphology, mesonephric-like adenocarcinoma follows an aggressive clinical course, characterized by frequent and early recurrences, most often in the lung. Accordingly, accurate distinction of mesonephric-like adenocarcinoma from morphologic mimics-especially low-grade endometrioid adenocarcinoma-is critical. However, available evidence indicates that endometrial mesonephric-like adenocarcinomas are significantly underdiagnosed, likely due to their relative novelty, rarity, and considerable overlap with endometrioid neoplasia. Prospective recognition of characteristic morphologic features, a low threshold for application of diagnostic immunohistochemistry, and judicious use of molecular studies will permit accurate diagnosis in almost all cases.
Mixed phenotype acute leukemias (MPALs) are a rare category of acute leukemia with biologic and genetic heterogeneity and a prognosis generally inferior to those of single lineage leukemias. The diagnosis depends on immunophenotypic assessment with a comprehensive panel of monoclonal antibodies by multiparameter flow cytometry and lineage assignment by the World Health Organization criteria. CD19 assessment is required for establishing a B-cell component in MPALs, as is determination of its intensity of expression, and assessment of the additional B-cell markers CD79a, cytoplasmic CD22, and CD10. We report the case of an MPAL, initially classified as an acute myeloid leukemia with weak CD19 expression and later reclassified upon clear demonstration of a B-cell component; such cases highlight a pitfall in classification of acute leukemias, particularly given heterogeneous antigen expression between fluorochromes and subjectivity in judgment of intensity. Practical take-away points include the need for hypervigilance in marker performance patterns in flow cytometry, both between fluorochromes and over time, the benefits of repeat sampling and blast assessment between laboratories, and the potential quality improvements unlocked by expanded flow cytometry panels in diagnostic hematopathology.
We report a case of chromophobe renal cell carcinoma (ChRCC) with extensive calcifications, which on biopsy was initially interpreted as a possible MiT translocation carcinoma, in part because of the young age of the patient. Upon resection, the tumor was typical for ChRCC. The tumor illustrates that calcifications may be prominent in ChRCC and that the most common tumors in young patients are sporadic and of the classic morphologic types.
In this issue of American Journal of Surgical Pathology: Reviews and Reports, we take a brief detour from the usual diagnostic focus of the journal, to discuss a potpourri of laboratory management issues in the anatomic pathology (AP) laboratory. Why would I do this to you? Why can't I just leave you to learn about cool tumors and grow your diagnostic skills? Anatomic pathologists care deeply about being the best diagnostician they can be. They work hard to learn diagnostic criteria, keep up with the latest literature, and carefully study each challenging case to arrive at the best possible diagnosis. But we fool ourselves if we believe that we can ignore everything that happens in the laboratory to get those slides to our office and that report to the patients and their providers. What good is the best diagnosis if the tumor tissue was actually a contaminant from another patient (Anderson, et al)? Or if the diagnosis is assigned to the wrong patient because of an accessioning error (Jacobs and Staats)? How sure are you that your clinician understands exactly what you have written in your report (Findeis, et al)? Laboratory management requires a different skill set and a willingness to work outside our natural comfort zone of traditional pathology training, but it is every bit as important to our patients as our diagnostic work, and people who are willing and able to do it are invaluable to the laboratory. Laboratory management is often categorized in residency programs as a clinical pathology rotation, and the clinical laboratories have without a doubt run ahead of AP in implementing many management and quality tools in the past, but today's modern AP laboratory is rapidly catching up in this regard, because of the pull of enlightened laboratory leadership realizing the value of these techniques, as well as the push of regulatory requirements. This issue focuses particularly on some of the unique aspects of laboratory management in AP. However, a single issue cannot possibly cover every aspect of AP laboratory management, and rather than focus narrowly on one specific area, this issue chooses to present articles touching on a wide range of topics. We start with a very common issue in AP: a discussion of a particularly challenging case of the dreaded "floater" by Anderson, Amin, and Bernacki. This common issue in AP poses a substantial risk to patients if the pathologist does not keep an open mind, and the investigation can be challenging. We then turn to a series of articles on quality metrics. DeSimone and Heher discuss the classic metric of "turnaround time" in a new light. Jacobs and Staats discuss the value and challenges of reporting and tracking errors in AP. Vander Laan discusses novel metrics to assess individual provider performance in the diagnosis of thyroid cytology specimens. Although focused specifically on thyroid cytology, this discussion also provides a framework for thinking about diagnostic metrics more broadly in pathology. Dahl, Myers, and Pantanowitz discuss the use of data-driven decision-making across a broad range of laboratory management issues. Next, we turn to postanalytic communication. First, Findeis, Huber, and Whitney-Miller discuss ambiguity in the written pathology report. Then, Kallen, Otis, and Staats discuss communication of urgent and significant unexpected (critical) diagnoses in AP. We close with an experience living through the unimaginable, as Stowman and Kalof detail the University of Vermont's experience with a nearly month-long complete technology shutdown following a cyberattack, and how an Incident Command Structure was used to regain laboratory function. I hope you enjoy this detour from diagnosis into laboratory management and that some of these articles cause you to think about a broader role for you as a pathologist in your laboratory, not just as a diagnostician but as a laboratory manager.
Flow cytometry (FC) is a powerful tool for characterizing hematopoietic cells and plays a critical role in the diagnosis and classification of hematopoietic neoplasms. However, its accuracy rate alone without morphology is questionable. It is imperative to always have clinical and morphologic correlation. Herein, we describe a case of nasal mass, which could have been misdiagnosed as a hematologic malignancy based on FC alone without morphologic examination.
A proportion of endometrial and adnexal carcinomas have concurrent involvement of the other site. In the case of high-grade serous carcinomas involving the tubal epithelium as well as endometrium, distinction of tubo-ovarian high-grade serous from endometrial serous carcinoma can have implications for surgical as well as nonsurgical treatment approaches, including targeted therapies and referral to clinical genetics services. The other situation is involvement of the endometrium and ovary by low-grade endometrioid carcinoma; here separation of high-stage endometrial carcinoma from 2 low-stage, low-grade tumors determines adjuvant treatment decisions. These challenging scenarios are illustrated with case presentations and criteria for pathological reporting while acknowledging uncertainty where this is warranted. It is accepted that these are areas in transition, and any criteria offered are likely to change in the light of new information.
Variant anatomy and cytomorphological overlap between benign and malignant conditions can coincide to produce diagnostic error. We report the case of an unusually shaped thyroid gland bearing a follicular adenoma interpreted as a metastatic papillary thyroid carcinoma. The shape of the gland had a striking resemblance to The Scream, a painting by Edvard Munch, and directly contributed to the misdiagnosis. We discuss the known embryological mechanisms of thyroid development, ultrasound radiological characteristics of thyroid examination, and the cytomorphologic interpretation of thyroid tissue. The constellation of these elements and the resultant error is eloquently illustrated by Munch's artistic inspiration.
Dear readers of AJSP: Reviews and Reports, I am thrilled to present a second issue on the subject of “My most memorable diagnostic mistake.” We all hope to never make them, and yet it happens to all of us, regardless of experience. The most important thing is that we learn from these mistakes, which is what inspired us to start publishing reports of real-life diagnostic errors, accompanied by an honest assessment of their causes and consequences and recommendations on how to prevent others from repeating them. We believe this will serve as a powerful teaching tool for the readers of our Journal, regardless of where in their pathology career they are. In this issue you will find a collection of notoriously hard diagnoses to make—common and rare—and honest discussions about ways to avoid making a mistake when dealing with them. It is not surprising therefore that the first 3 articles are devoted to mesothelial lesions in all their treacherous perturbations. Burke and colleagues start this issue with a detailed and practical review of an exquisitely difficult dilemma for any surgical pathologist: sarcomatoid mesothelioma and its distinction from a reactive process. Immunohistochemistry is an extremely valuable tool in the workup of possible mesothelioma and its differential diagnosis; however, it can also become a pitfall, as shown in the wonderfully thorough and helpful review by Stashek et al. Another example of a diagnostic issue regarding peritoneal mesothelial proliferations is provided by Burke and Legesse. Their report illustrates the difficulty in distinguishing reactive and neoplastic peritoneal mesothelial processes and offers very helpful guidance for this differential diagnosis. Elishaev et al deliver a great example of the often frustratingly difficult differential diagnosis of mucinous tumors of gynecologic and gastrointestinal origin. The thorough summary of helpful features will be no doubt useful to practicing pathologists faced with this common dilemma of separating metastatic spread from primary ovarian tumors. Another difficult instance of metastatic malignancy mimicking a primary tumor is described by Fanaroff and Burke in a beautifully illustrated report. It is well established that pitfalls in hematopathology abound. The next 3 articles showcase these difficulties really well. The first, by Kallen and colleagues, describes a situation where flow cytometry may hinder the diagnosis instead of facilitating it. The authors perform a root-cause analysis of the error and address the need to carefully review all available information, as well as to pay constant attention to quality assurance efforts in the laboratory. The article that follows expands further on the dangers of using ancillary studies, such as flow cytometry, in separation from clinical data and morphologic examination. The authors, Aqil and Ramos, make a compelling case for integrating all available information when making such complex diagnoses as hematologic malignancies. This section is concluded by a very interesting report of an ALK-positive anaplastic large cell lymphoma, which presented with a leukemic picture and was initially diagnosed as T-cell prolymphocytic leukemia. The differential diagnosis of these entities is masterfully presented by Vadasz et al. Every pathologist knows how treacherous thyroid carcinoma metastases are due to their benign appearance and presence in unexpected locations. The report or, rather, cautionary tale by Wiles and Sayeedi is that of a diagnostic error of an opposite direction: an unusual, distorted shape of a benign thyroid gland interpreted as a lymph node with metastatic papillary thyroid carcinoma, which led to total thyroidectomy. The authors carefully dissect factors that caused the mistake and provide ample advice on how to avoid similar errors. Nonneoplastic liver pathology is notoriously difficult, and the case reported by Alkahash et al is no exception. The authors describe a case of end-stage liver disease necessitating liver transplant that was presumed to be secondary to cirrhosis; the cause, however, was discovered to be vascular in nature: the culprit was portosinusoidal vascular disease or idiopathic noncirrhotic portal hypertension—an exceedingly difficult diagnosis, for which the authors provide a very helpful diagnostic algorithm. Mimickers in our field are numerous; many of them are well known, some are uncommon. The first of the following 2 articles describes a very rare mimicker—all the more dangerous because of its rarity: renal cell carcinoma seen in a urine cytology specimen and mistaken for high-grade urothelial carcinoma. The next case report in this issue concerns 2 common and infamous mimickers: melanoma and angiosarcoma. Both are known to mimic other tumors, and we are trained to always consider them in the differential diagnosis of almost any tumor in any location. This case, however, illustrates a doubly dangerous scenario: poorly differentiated angiosarcoma that was initially interpreted as melanoma, both clinically and pathologically. Truly, a warning to all of us! To conclude, I promise more issues in the future devoted to an honest and open discussion of memorable diagnostic mistakes; may we all learn from these so as not to make them ourselves!
Abstract Ovarian neoplasms are a common specimen received for intraoperative consultation (frozen section) as an accurate diagnosis is necessary to determine the next steps in surgery. We present the case of a 79-year-old woman with a 5.3-cm right ovarian lesion as well as a large appendiceal mass. The frozen section of the ovarian lesion showed a high-grade tumor with areas of luminal necrosis. These morphologic findings, along with the presence of a colonic mass, led to an intraoperative consultation diagnosis of “high grade adenocarcinoma, favor metastasis from gastrointestinal tract primary,” and to the surgery ending after removal of the appendix and cecum. However, the permanent section revealed high-grade serous carcinoma. We review the differential diagnosis of high-grade ovarian lesions on frozen section, examine the challenges that can occur, and discuss the potential downstream effects and consequences for patient care.
Abstract Benign inclusions in lymph nodes are a rare phenomenon that has been described throughout the body. These foci of nonneoplastic, ectopic tissue in the axillary lymph nodes can mimic low-grade metastatic breast carcinomas and result in a diagnosis of false-positive nodes that would lead to unnecessary treatment. We present a challenging case of a patient with a left breast grade 1 invasive ductal carcinoma undergoing an intraoperative axillary sentinel lymph node frozen-section consultation that contained numerous small tubules in the subcapsular space. The lymph node was interpreted as positive for carcinoma, and the patient underwent an axillary lymph node dissection. On permanent sections, myoepithelial cells and surrounding basement membranes were identified around some of the tubules, and a large, squamous inclusion cyst became visible. Immunohistochemical stains were performed that showed that p63 and smooth muscle myosin heavy chain highlighted myoepithelial cells around the tubules, whereas cytokeratin 5/6 and estrogen receptor stains showed a mosaic pattern of positivity. Combined, these findings supported a revised diagnosis of benign glandular and benign squamous inclusions. This case underscores the importance of thoroughly examining the location and histologic and cytologic features of a low-grade–appearing epithelium before determining lymph node positivity and, if it is unclear, deferring the diagnosis to permanent sections where immunohistochemical stains can be performed. Knowledge of this uncommon finding is important to avoid false-positive results, unnecessary treatments, and their associated comorbidities.
