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| Email: | mcl@mayo.edu |
| Telephone: | 800-533-1710 |
| International: | +1 855-379-3115 |
| Values are valid only on day of printing | |
A 59-year-old woman presenting with pruritic/burning skin rash, proximal muscle weakness, electrolyte disturbance, and abdominal fullness. Imaging revealed a 7 cm lobulated left paracentral pelvic/adnexal mass abutting the sigmoid colon, associated with ascites and abdominal lymphadenopathy. The patient underwent en-block resection and a pelvic washing for cytology evaluation at the time of the procedure.
The correct answer is ...
Embryonal rhabdomyosarcoma.
This case was signed out on the surgical specimen as embryonal rhabdomyosarcoma involving left ovary, fallopian tube, and para-adnexal soft tissue.
Rhabdomyosarcoma (RMS) is the most common soft-tissue malignancy of childhood and adolescence, however, adult RMS is rare, representing only 3% of soft tissue tumors and less than 1% of all adult malignancies. Primary abdominopelvic RMS is exceedingly uncommon, with only a few cases reported in the literature involving the fallopian tube and ovary as primary locations. The largest reported series of primary ovarian RMS is by Nielsen et al in 1998, and it included 13 cases in patients with age varying from 7 to 79 years.
Histomorphologically, RMS exhibit patternless sheets of spindled, stellate, and ovoid cells with variable skeletal muscle differentiation. Typically, the embryonal subtype (ERMS) has primitive small cells with scant cytoplasm and abundant apoptoses. Rhabdomyoblasts with abundant eosinophilic cytoplasm (when elongated, called strap cells) with or without cross striations and multinucleated giant cells can also be seen. Mitotic activity is variable but often brisk. ERMS characteristically stain positive for desmin, myogenin, and myoD1 (typically coexpression of desmin and myogenin), assisting with differential diagnosis with other small round cell tumors. Rarely, the tumor cells can stain positive with CD99, cytokeratin, EMA, S100, ER, PR, or WT1. High Ki-67 expression is observed, especially in hypercellular areas.
Metastatic sarcomas, including RMS, are rarely diagnosed in body fluids. Sarcoma cells in fluids can round up and lose the characteristic appearance seen on tissue biopsy, posing diagnostic challenges. Several studies have looked into the shared cytomorphologic features of sarcomas in body fluids, which can include single or small clusters of cells, large tumor cells, and occasional multinucleated giant cells. Prominent nucleoli and the chromatin patterns vary from case to case. Cytoplasm tends to be scant in nature and features of mesenchymal differentiation can be seen in some specimens. Mitoses are usually absent, even when easily identifiable on corresponding histologic sections. Knowledge of prior history and high level of suspicion are helpful in achieving the correct diagnosis.
Several genetic alterations have been associated with RMSs, one of which is DICER1 mutations (germline or somatic) that have been shown to be associated with ERMS cases of the cervix and genitourinary tract. DICER1 syndrome is a hereditary cancer predisposition syndrome that can result in a variety of “hyperplastic” disorders and uncommon neoplasms including various benign and malignant thyroid neoplasms, pleuropulmonary blastoma, ovarian Sertoli-Leydig cell tumor (SLCT), and ERMS of the cervix and genitourinary tract.
The presence of primitive-appearing glands containing cytoplasmic vacuoles, which stain positive for SALL4 immunostain, and presence of cartilage foci that might be cytologically atypical, an uncommon finding in ERMS of other sites, should alert the pathologist for the possibility of an associated DICER1 mutation.
Farah Baban, M.B., Ch.B.
Fellow, Cytopathology
Mayo Clinic
@Baban.Farah
Diva Salomao, M.D.
Consultant, Anatomic Pathology
Mayo Clinic
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science
@DivaRSalomao
A 70-year-old woman has a chief complaint of melena. She has a past medical history of chronic lymphocytic leukemia and metastatic breast cancer. Her breast cancer is currently being treated with paclitaxel and pembrolizumab. She undergoes colonoscopy, which is essentially normal. Biopsies of the colon show colonic mucosa with marked crypt apoptosis. The findings are suggestive of drug injury. This pattern is described in immune checkpoint inhibitor associated colitis.
The correct answer is ...
Paclitaxel.
In addition to pembrolizumab, the patient was treated with paclitaxel, which can show a pattern of injury of ringed mitoses. The other answer choices all can show an apoptotic colopathy picture of injury.
Rosalie Sterner, M.D., Ph.D.
Resident, Anatomic & Clinical Pathology
Mayo Clinic
Christopher (Chris) Hartley, M.D.
Consultant, Anatomic Pathology
Mayo Clinic
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science
A 27-year-old woman presented with shortness of breath, tachycardia, fever of unknown origin, widespread lymphadenopathy, general malaise, and weight loss. A fine needle aspiration and core biopsy of an enlarged cervical lymph node is performed. Representative photomicrograph including H&E and immunohistochemistry are shown below. Molecular analysis was positive for a T-cell gene rearrangement.
The correct answer is ...
ALK-positive anaplastic large cell lymphoma (ALCL).
The histologic sections show an atypical lymphohistiocytic infiltrate with a significant population of large, atypical cells. Many of these cells have ample eosinophilic cytoplasm and round to horseshoe-shaped nuclei with prominent nucleoli (so-called “hallmark” cells). The provided immunohistochemistry images demonstrate that these cells are positive for CD30 (strong uniform), ALK, CD2 (weak), PAX5 (weak, granular staining), and are negative for CD3 and CD20. This phenotype is not sufficient to establish T-cell lineage on its own and could be seen in either B-cell or T-cell lineage neoplasms. In combination with the molecular results, which were positive for a T-cell gene rearrangement indicating T-lineage, the findings are diagnostic for ALK-positive ALCL.
In this case, the tumor cells were also positive for CD4, CD7 (partial/weak), CD45, and granzyme B, and negative for CD8, CD15, TCR beta F1, TCR delta, and cytokeratin AE1/AE3 (not shown). Loss of T-cell antigens such as CD3, as seen in this case, is very common in ALCL and can pose a significant diagnostic challenge. There was also aberrant expression of a B-cell lineage-associated marker PAX5. Aberrant PAX5 in ALCL is uncommon and often adds even more challenge for the pathologist, when Hodgkin's lymphoma or ALK(+) large B-cell lymphoma can enter the differential. Cases of ALCL with aberrant PAX5 expression often require molecular confirmation of lineage, as performed in this case.
In contrast to ALK-negative ALCL, ALK-positive ALCL tends to occur in children and young adults, and often presents with widespread lymphadenopathy and extranodal disease. ALK-positive ALCL also tends to have a better prognosis than its ALK-negative counterpart. This disease generally responds favorably to treatment with systemic chemotherapy and has a 5-year overall survival rate of 85%.
The large cell size and cohesiveness of this neoplasm is reminiscent of a metastatic carcinoma. While carcinoma is certainly on the differential diagnosis of ALK-positive anaplastic large cell lymphoma, and some carcinomas can display ALK positivity, CD30 and other hematopoietic markers would be negative. Metastatic carcinoma is excluded by establishing T-cell lineage in this case.
Another diagnostic consideration is classic Hodgkin's lymphoma, as ALCL hallmark cells may resemble Reed-Sternberg/Hodgkin cells, and both are positive for CD30, and this case also showed partial positivity for PAX5. The strong uniform expression of ALK by immunohistochemistry reveals the underling genetic aberrancy and excludes Hodgkin's lymphoma in this case.
ALK-positive large B-cell lymphoma may also be considered in the differential diagnosis of ALK-positive anaplastic large cell lymphoma. The neoplastic cells in this entity are large and have abundant cytoplasm and may resemble either plasmablasts (with eccentric nuclei) or immunoblasts (with central nuclei and prominent nucleoli). They typically have a phenotype more akin to plasma cells, with positivity for CD138, MUM1, and other plasma-cell associated markers; CD30 is only rarely focally or partially expressed. In this case, this diagnosis is excluded by strong uniform expression of CD30 and the presence of a T-cell gene rearrangement.
Clarissa Jordan, M.D.
Resident, Anatomic & Clinical Pathology
Mayo Clinic
@pathcejmd
Daniel (Dan) Larson, M.D.
Senior Associate Consultant, Hematopathology
Mayo Clinic
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science
@DanLarsonMD1
A 9-year-old boy presented for evaluation of a right mandibular lesion. He denied having any pain associated with the area or neurosensory changes along the inferior alveolar nerve region. Imaging showed a mixed radiolucent/radiopaque lesion in the right mandible angle region. Enucleation and curettage of the posterior mandibular lesion was performed. Histologic sections show small islands of odontogenic epithelium surrounded by odontogenic ectomesenchyme (primitive dental papilla-like) containing dentin and enamel (Figure 1).
The correct answer is ...
Ameloblastic fibroma/Fibro-odontoma.
Ameloblastic fibroma (AF)/Fibro-odontoma (AFO) is a benign mixed epithelial and mesenchymal odontogenic tumor. It is more commonly encountered in the first two decades of life (mean patient age is 15 years old, with 80% of lesions occurring before age 22). These lesions present with a higher frequency in the posterior mandible. Radiographically they are well-defined and corticated, usually unilocular and associated with unerupted teeth and some can have a radiolucent-radiopaque appearance (Figure 1A, arrow).
AF is associated with BRAF p.V600E mutation in 46% of cases. Histologically, the lesions are composed of an evenly hypercellular myxoid, primitive-appearing mesenchymal component, resembling the developing dental papilla. The admixed epithelial component resembles ameloblastoma and is comprised of islands, cords, and strands of bilaminar cuboidal to columnar palisaded cells surrounding areas of stellate reticulum-like tissue, reminiscent of the follicular stage of the enamel organ (Figure 1 B-C). In the 2022 WHO Classification of Tumors, lesions previously diagnosed as ameloblastic fibro-odontoma and ameloblastic fibro-dentinoma (AFD) are now mentioned in the AF and odontoma sections as histologically intermediate between AF and odontomas; however, their status is still debated. Histologically, AFO and AFD resemble AF, but they also contain dental hard tissue matrix such as dentin and enamel (Figure 1 C-D). Clinically these lesions are usually treated with curettage and have a low rate of recurrence.
Ameloblastoma can be differentiated from ameloblastic fibroma/fibro-odontoma based on radiologic features (multilocular, corticated, radiolucent lesions with a “soap-bubble” appearance), age at time of presentation (peak incidence in the fourth and fifth decades of life), and histological characteristics including absence of the hypercellular myxoid mesenchymal component and lack of dental hard tissue matrix, such as dentin and enamel. It is important to differentiate ameloblastoma from its mimics due to its high rate of recurrence and the requirement for complete resection with negative bone margins (1 cm).
Odontomas are mixed odontogenic hamartomas, predominantly composed of dental hard tissues with small components of odontogenic epithelium and primitive mesenchyme. Developing odontomas may exhibit overlapping morphologic features with AF/AFO and correlation with clinical and imaging findings may be helpful.
Odontogenic myxoma is composed of sparse stellate, spindled and round cells within a prominent, loose, myxoid stroma with scant collagen fibers, and occasional small rests of inactive odontogenic epithelium. The stroma is typically hypocellular and lacks the primitive appearance, as well as the ameloblastic epithelium.
Veronica Ulici, M.D., Ph.D.
Fellow, Surgical Pathology
Mayo Clinic
David Schembri Wismayer, M.D.
Consultant, Anatomic Pathology
Mayo Clinic
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science
Anja Roden, M.D.
Consultant, Anatomic Pathology
Mayo Clinic
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science
The patient is a 71-year-old woman who presented with dyspnea, chronic cough, and intermittent fever. Cross-sectional thoracic imaging demonstrated bilateral pulmonary opacities and a focal right lower lobe density on a chest CT (Figure 1; imaging). A lung biopsy was performed (Figures 2 and 3; pathology).
The correct answer is ...
Exogenous lipoid pneumonia.
Exogenous lipoid pneumonia is a form of aspiration pneumonia caused by either the aspiration or inhalation of lipid-containing products, most often nasal decongestants or other oil-based products. More recently, this condition has been associated in case reports with vaping, which is the use of electronic cigarettes that produce an inhalable aerosol composed of nicotine, flavorants, oils, and other chemicals. These processes and etiologies are in contrast to endogenous lipoid pneumonia, which is usually associated with airway obstruction.
The biopsies in this case show alveolated parenchyma with patchy interstitial thickening and a cellular process within airspaces. Variably sized vacuoles distend the cytoplasm of reactive macrophages, occasionally forming focal multinucleated giant cells within alveolar spaces and in the interstitium. Colorless, dot-like refractile material can be identified within a subset of the vacuoles.
This histologic impression is representative of the underlying pathophysiology of this condition. As lipid material is introduced into the airspaces, it recruits a foreign-body reaction due to the accumulation of insoluble material within the cytoplasm of macrophages. This manifests as variably sized vacuoles associated with histiocytic inflammation including multinucleated foreign body-type giant cells and, in chronic conditions, reactive fibrosis.
The radiological findings in lipoid pneumonia are nonspecific, with variable patterns and distributions of consolidation. Most often, however, the lower lung fields are disproportionately affected. As such, biopsies are generally favored to establish a histological diagnosis or confirmation of a clinically suspected process. The prognosis of exogenous lipoid pneumonia is generally favorable; however, cases with significant chronicity can display irreversible parenchymal fibrosis.
Nicholas Boire, M.D., M.S.
Resident, Anatomic & Clinical Pathology
Mayo Clinic
@NicholasBoireMD
Melanie Bois, M.D.
Consultant, Anatomic Pathology
Mayo Clinic
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science
@MelanieBoisMD
The correct answer is ...
Light chain proximal tubulopathy (LCPT), kappa-restricted, with crystals.
LCPT is a monoclonal gammopathy of renal significance (MGRS) characterized by light chain deposition that occurs intracellularly, within proximal tubular cells.1 Immunoglobulin light chains can be mutated in the variable domain, become resistant to intracellular enzymatic breakdown, and eventually form intracytoplasmic crystals (particularly when the κ light chain precipitates, like in the current case); the light-chain crystals disrupt lysosomal function and induce cell injury.2,3 The proximal tubular dysfunction can manifest as chronic kidney disease and/or Fanconi’s syndrome and electrolyte disturbances. When crystals are present, standard immunofluorescence could be negative and pronase digestion for antigen retrieval should be performed.1
Many patients with this condition have an underlying plasma cell dyscrasia, including multiple myeloma, which may not be known at the time of the kidney biopsy.4 In fact, once a diagnosis of LCPT is made, a laboratory workup to exclude a hematologic malignancy is warranted.
Incorrect answers:
Light chain cast nephropathy: Light chain cast nephropathy is characterized by crystalline precipitates of monoclonal light chain (either κ or λ) within the lumen of distal tubules.
Heavy chain deposition disease (HCDD): It is a rare monoclonal immunoglobulin deposition disease (MIDD) characterized by glomerular mesangial nodular sclerosis on light microscopy, and finely granular, powdery deposits along the basement membranes. As the name describes, this entity is characterized by deposition of monotypic mutated heavy chains (not light chains) by immunofluorescence (usually IgG). Therefore, “HCDD, kappa-restricted” not only is the incorrect answer but is also conceptually incorrect.
Light chain deposition disease (LCDD): It is an MIDD characterized by deposition of monotypic immunoglobulin light chains. Histologically, it is distinguished from HCDD by the immunofluorescence findings (either κ or λ light chain-restriction, without monotypic heavy chains).
Alessia Buglioni, M.D.
Fellow, Anatomic Pathology
Mayo Clinic Scholar
Mayo Clinic
Loren Herrera Hernandez, M.D.
Consultant, Anatomic Pathology
Mayo Clinic
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science
Mariam (Priya) Alexander, M.D.
Consultant, Anatomic Pathology
Mayo Clinic
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science
A 3-year-old boy with a medical history of short gut syndrome was admitted to the hospital due to intermittent abdominal distention, pain, and fever. During his admission, his INR was elevated at 2.0. To address this laboratory finding, the clinical team ordered one unit of fresh frozen plasma (FFP). During the transfusion of the FFP, the patient developed facial swelling and hives throughout his body. He also had increased output from his ileostomy, decreased blood pressure (from 92/54 to 79/46 mmHg), decreased oxygen saturations (from 96% to 92%), and increased heart rate (from 116 to 144 bpm). Intramuscular epinephrine and intravascular Benadryl, steroids, and Famotidine were given, which resulted in resolution of his hives and return to pre-transfusion vital signs. Clerical check, DAT, and hemolysis check were all negative/unremarkable. A chest X-ray was unremarkable and did not demonstrate pulmonary infiltrates.
The correct answer is ...
Anaphylactic transfusion reaction.
TACO is associated with dyspnea, tachycardia, hypertension, and jugular venous distension. As the patient developed hypotension rather than hypertension, and there was a lack of evidence suggestive of volume overload or pulmonary infiltrates seen on chest X-ray, TACO is unlikely.
TRALI is associated with fever, hypotension, acute respiratory distress with hypoxemia, and bilateral pulmonary edema, often seen as bilateral “fluffy” pulmonary infiltrates on chest X-ray, which can often be described as “pulmonary white-out.” The patient did not present with fever and the chest X-ray was unremarkable without pulmonary infiltrates. The resolution of the patient’s symptoms and return to baseline vitals after administration of epinephrine and Benadryl, make TRALI less likely.
As the clerical check, DAT, and hemolysis check were all negative/unremarkable, an acute hemolytic transfusion reaction is also unlikely.
This patient most likely experienced an anaphylactic transfusion reaction. These reactions are usually idiopathic. Rarely they are attributable to specific antibodies to donor plasma proteins (e.g., anti-IgA antibodies or anti-haptoglobin antibodies). Patients can present with hypotension, facial edema, rash, pruritis, urticaria, stridor, coughing, wheezing, and hypoxemia. As in most cases, the cause of anaphylactic reactions is unknown. Thus, for future blood transfusions, patient will require washed cellular blood products (red blood cells and platelets) prior to transfusion. Acellular blood products (plasma and cryoprecipitate) cannot be washed and should only be transfused after consultation with the transfusion medicine service to ensure clinical awareness of the potential for an additional anaphylactic reaction that may require immediate medical intervention.
Monica Klein, M.D.
Fellow, Transfusion Medicine
Mayo Clinic
Camille van Buskirk, M.D.
Consultant, Transfusion Medicine
Mayo Clinic
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science
