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| Web: | mayocliniclabs.com |
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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 74-year-old man presented with symptoms of ongoing fatigue. His serologic studies demonstrated a minimally elevated prolactin, a borderline low cortisol, low gonadotropins, and a borderline low free T4. An MRI demonstrated a 2.2 x 2.4 x 1.9 cm heterogeneously enhancing mass filling and expanding the sella. He subsequently underwent a brain biopsy.
The correct answer is ...
The diagnosis in this case is: spindle cell oncocytoma.
Spindle cell oncocytoma (SCO) is a rare, non-neuroendocrine neoplasm of the posterior pituitary gland. This entity was originally described in 2002 by Roncaroli et al., and, based on ultrastructural characteristics, was hypothesized to originate from folliculostellate cells of the anterior pituitary gland.1 By microscopy, SCO are typically composed of fascicles and lobules of spindle to epithelioid [TLL1] cells with a variable amount of eosinophilic cytoplasm [Figures 2-4].2 By immunohistochemistry, SCO typically express TTF-1 and S100 with variable expression of GFAP and EMA [Figure 5]. SCO are negative for chromogranin [Figure 5].2
The cell of origin of SCO is still unresolved. However, more recent studies suggest that the shared TTF-1 immunoreactivity of non-neoplastic pituicytes, pituicytomas, granular cell tumors, and SCO may suggest a similar origin of these tumors from the pituicytes of posterior pituitary gland.3-4 The three morphologically distinct tumors from pituicytes may be linked to the existence of multiple subtypes of pituicytes in the normal neurohypophysis and their shared ultrastructural characteristics. 4-5
Ultrastructurally, the neoplastic cells of SCO often are filled with mitochondria [Figures 6-7[TLL2] ]. This is in contrast to granular cell tumor of the sellar region, which is typically negative for GFAP and by electron microscopy has lysosome-rich cytoplasm.2
Pituitary adenoma is an incorrect answer in this case. SCO can present with identical clinical symptoms and imaging findings to a nonfunctioning pituitary macroadenoma [Figure 1]. However, by immunohistochemistry pituitary adenoma is positive for chromogranin and negative for TTF-1.2 Schwannoma is an incorrect answer in this case. Schwannomas have rarely been reported as occurring in the sellar region and may have similar clinical symptoms to a nonfunctioning pituitary macroadenoma.6 A helpful distinguishing feature from SCO is that schwannomas are negative for TTF-1 by immunohistochemistry.2
Kathryn Eschbacher, M.D.
Resident, Anatomic Pathology and Neuropathology
Mayo Clinic
Aditya Raghunathan, M.D., M.P.H.
Consultant, Anatomic Pathology
Mayo Clinic
Associate Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science
A 23-year-old woman received the following punch biopsy for a tan-yellow pigmented ankle lesion.
The correct answer is ...
The diagnosis in this case is: Necrobiosis lipoidica.
Necrobiosis lipoidica (NL) is a poorly understood granulomatous disease of the dermis and subcutaneous tissue that is associated with a variable clinical course. The incidence for this condition is 0.3% of patients with diabetes mellitus with a female predominance, yet it may also present in healthy individuals.1 Additional systemic conditions associated with NL include systemic lupus erythematosus, hypothyroidism, ulcerative colitis, and rheumatoid arthritis.2
To date, the underlying pathogenesis for necrobiosis lipoidica remains unknown, yet numerous theories exist. Some have hypothesized that the pathophysiology of NL involves microangiopathy secondary to glycoprotein deposition in vessel walls; immune complex deposition; development of anti-collagen antibodies; or venous insufficiency.3,4,5
NL is usually characterized by bilateral lower extremity lesions, typically along the pretibial surface that are first visible as either papules or nodules that may progress to waxy yellow-brown plaques. Ulcerations may also develop, particularly following trauma.6 Differential diagnoses based on the clinical presentation and lesion location often include other granulomatous disorders, including necrobiotic xanthogranuloma (NXG), granuloma annulare, sarcoidosis, erythema nodosum, as well as venous stasis ulcers. The need to differentiate amongst these disparate entities underscores the importance of obtaining a biopsy. Histopathologic features of NL biopsy specimens at low magnification exhibit alternating horizontal layers of necrobiosis in a “layer cake” pattern involving the superficial dermis and subcutaneous fat. The epidermis is typically normal but may also demonstrate atrophy, acanthosis, or hyperkeratosis. The palisading necrobiotic granuloma is composed of epithelioid histiocytes and giant cells, occasionally arranged in well-formed granulomas. Additional cell types such as lymphocytes and plasma cells are often present in clusters. Alternating between the granulomas are layers of eosinophilic swollen, degenerative, collagen fibers.
Belinda Galeano, M.D., Ph.D.
Resident, Anatomic and Clinical Pathology
Mayo Clinic
Julia Lehman, M.D.
Consultant, Laboratory of Dermatopathology
Mayo Clinic
Professor of Dermatology and Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science
The lab receives a blood sample from Maternal Fetal Medicine with an order to perform a Fetomaternal Bleed, Flow Cytometry test. The mother is Rh negative, and the team needs to know how much Rh Ig to administer. When the sample is run, it is determined that the mother has a hemoglobinopathy — hereditary persistence of fetal hemoglobin — that complicates the interpretation of the results.
The correct answer is ...
The diagnosis in this case is: Obtain a new blood sample and order a flow cytometry test that includes an antibody for carbonic anhydrase.
Correct answer: By ordering a flow cytometry test that includes antibodies for hemoglobin F (HbF) and carbonic anhydrase (CA), one could discriminate between fetal and maternal HbF+ cells. Fetal RBCs will be negative for CA while the mother’s RBCs will stain positive for both HbF and CA. Incorrect answers: There are multiple methods to identify HbF+ cells.1 Unfortunately, the Kleihauer-Betke assay is a quantification test and is not able to reliably separate maternal and fetal HbF+ cells.2 The same is true when running a flow test with a CD36 antibody, which will label both maternal and fetal cells as well as other cell types, preventing proper interpretation of the flow results.3
Ashley Krull, Ph.D.
Fellow, Cellular Therapy
Mayo Clinic
@AshleyAKrull
Margaret DiGuardo, M.D.
Senior Associate Consultant, Laboratory of Transfusion Medicine and Clinical Genomics
Mayo Clinic
A 72-year-old man with a past medical history of polymyositis managed with IVIG presents with worsening dyspnea on exertion. He presented to the emergency department and was noted to have oxygen saturations at 83%. A computed tomography scan demonstrates newly developed diffuse, bilateral ground glass opacities. He was admitted and placed on 4L supplemental oxygen, but gradually declined despite standard immunosuppressive care, ultimately requiring mechanical ventilation support. IgG anti-Jo1 levels were noted at >8.0 U.
The correct answer is ...
The diagnosis in this case is: Anti-synthetase syndrome with associated interstitial lung disease. Therapeutic plasma exchange should be started.
This is a case of anti-synthetase syndrome with associated interstitial lung disease. The classic example of this disease is polymyositis with anti-Jo1 antibodies. This general diagnosis encompasses many rheumatologic diseases characterized by inflammatory muscle disease, pulmonary and joint inflammation, interstitial lung disease, and anti-synthetase antibodies such as anti-Jo1, -SSA, -Smith/RNP, -PL7/12, -EJ, -OJ, -SRP, -Ku, -SCL-100, -Fibrillarin, -Mi-2, -P155/140, -TIF-1 gamma, -SAE1, -NXP2, and -MDA5. Current first-line therapy includes corticosteroids or other immunosuppressive agents, which are often used in combination.
Dermatomyositis/polymyositis, two examples of anti-synthetase associated syndromes, are category IV indications for therapeutic plasma exchange (TPE) according to the 2019 American Society for Apheresis guidelines. Category IV indications for apheresis are “disorders in which published evidence demonstrates or suggests apheresis to be ineffective or harmful.” Category I indications for apheresis are “disorders for which apheresis is accepted as first-line therapy, either as a primary stand-alone treatment or in conjunction with other modes of treatment.” Category II indications are “disorders for which apheresis is accepted as second-line therapy, either as a stand-alone treatment or in conjunction with other modes of treatment.” Current guidelines for dermatomyositis/polymyositis focus on treatment of cell mediated tissue damage without recommendations for antibody mediated disease. As such, TPE for anti-synthetase syndrome with interstitial lung disease is better described as an uncategorized indication for TPE.
A recent body of case reports demonstrates effective intervention with therapeutic plasma exchange or column filtration plasmapheresis in individuals with anti-synthetase syndromes with interstitial lung disease resistant to medical management. At the time of publication, the ASFA guidelines considered inclusion of a fact sheet for anti-synthetase syndrome for which identifiable antibodies are detected in the setting of interstitial lung disease. Of the cases reported in the literature, stabilization of or improvement in respiratory function and chest radiograph findings has been documented in most cases. This is a disease category for which the role of apheresis is evolving, and further recommendations for intervention will hopefully be included in the next iteration of the ASFA guidelines.
Thomas Thompson, M.D.
Fellow, Transfusion Medicine
Mayo Clinic
@TZThompsonMD
Jeffrey Winters, M.D.
Consultant, Transfusion Medicine
Mayo Clinic
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science
@Pathdocjlwint
Liver explant (40x, HE & PAS-D stain), 30-year-old man with cirrhosis.
The correct answer is ...
The diagnosis in this case is: SERPINA1.
Yaohong Wang, B.Med, PhD
Fellow, Gastroenterology & Liver Pathology
Mayo Clinic
Zhang Lizhi, MD
Consultant, Anatomic Pathology
Mayo Clinic
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science
A 70-year-old woman with a history of living-related renal transplant and Crohn’s disease presents shortness of breath, sore throat, a hoarse voice, and weight loss. She is currently receiving immunosuppressive therapy to maintain her transplanted kidney. Routine labs demonstrated elevated leukocytes with a neutrophilic predominance, with imaging highlighting a soft tissue mass in the right posterior pharynx. Diagnosis on frozen section was requested and showed multiple budding yeasts.
The correct answer is ...
The diagnosis in this case is: Blastomyces dermatitidis/B. gilchristii.
Blastomyces dermatitidis and B. gilchristii are the causative agents of blastomycosis. Blastomycosis is an invasive and sporadic fungal infection that may present as an insidious and sometimes fatal fungal pneumonia throughout regions where it is endemic. It is endemic in select regions of Africa,1 and the central and eastern United States and Canada, surrounding the Ohio and Mississippi river valleys and the Great Lakes. It shares some geographical overlap with histoplasmosis, which is also found along the Ohio and Mississippi river valleys.2 First described in 1894 by Thomas Gilchrist, it can sometimes be found in the literature as “Gilchrist’s disease.”
Blastomyces spp. are thermally-dimorphic fungi, a distinction which signifies growth in a mold form at environmental temperatures, and in a yeast form when grown in a warmer animal host. Of the dimorphic fungi, Blastomyces spp. can be differentiated by their fairly uniform and large size (ranging from 8–15 um), broad-based budding, and a thick, double-layered cell wall. They are readily identifiable on routine hematoxylin/eosin and Grocott’s methenamine silver staining, and are commonly seen in a mixed granulomatous and suppurative inflammatory (i.e., pyogranulomatous) background. Blastomycosis involving the squamous epithelium (such as in this case) is commonly associated with pseudoepitheliomatous hyperplasia, which may be mistaken for squamous cell carcinoma.3 Therefore, a careful search for budding yeasts within areas of neutrophilic inflammation and within multinucleated giant cells is indicated.
Blastomyces dermatitidis and B. gilchristii are morphologically indistinguishable, therefore additional testing such as PCR may be needed to differentiate them. Species identification is not necessary for treatment and is infrequently performed.
The fungus can be found throughout the environment, favoring moist soil and decomposing organic matter (e.g. trees and leaves). Infection can occur after an environmental exposure if the individual breathes in the microscopic fungal spores. Approximately one-half of those infected with the fungus experience symptoms, which typically present with nonspecific signs: fever, cough, muscle pain, shortness of breath, and weight loss. Patients with a long-standing infection and immunocompromised patients can exhibit more severe disease as the fungus disseminates throughout the body.4 The skin is most commonly affected, but can also disseminate to the central nervous system, genitourinary, and skeletal sites.
A combination of clinical features (especially one’s travel history,) biopsy, fungal culture, and morphological assessment are used to diagnose the infection. When possible, histopathological sectioning is helpful in highlighting its association with pyogranulomatous response.5 Commercially available serum and urinary antigen testing is available and has shown to be sensitive in instances where fungal cultures are negative.
Nicholas Boire, M.D., M.Sc.
Resident, Anatomic and Clinical Pathology
Mayo Clinic
@NicholasBoireMD
Bobbi Pritt, M.D., M.Sc., DTMH, FCAP
Consultant, Laboratory of Clinical Microbiology
Mayo Clinic
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science
@ParasiteGal
