17 January 2022: Textbook Updates

We have posted updates of the following topics:

Bone & joints > Other chondrogenic tumors > Subungual exostosis
by Anshu Bandhlish, M.D., Jose G. Mantilla, M.D.
Topic summary: Rare, benign osteocartilaginous lesion arising from the distal phalangeal bone below the nailbed, lacking connection between the stalk of the lesion and medullary cavity of the native bone. More than 50% of cases are in patients younger than 18 years (average age: 25.7 years). Local recurrence is seen in cases after incomplete excision in approximately 4% of cases; no malignant transformation or metastasis has been reported. Complete marginal excision with minimal trauma to the nailbed is the optimal treatment.

CNS nontumor > Infections > Acute bacterial infections > Abscess
by Dennis K. Burns, M.D.
Topic summary: Localized, space occupying lesion within the brain composed of purulent (neutrophil rich) exudate and other inflammatory cells reacting to the presence of bacteria within the CNS parenchyma. Streptococcus spp. are the most common pathogens, although a wide range of organisms can cause disease; culture negative cases are not uncommon. Mortality ~10% in developed countries; old age, delayed diagnosis and treatment, ventricular rupture, rapid progression of symptoms and coma associated with poorer prognosis. Optimum management involves multidisciplinary approach (neurosurgery, infectious disease, neuroradiology, pathology and neurology).

Coagulation > Coagulation laboratory tests > PT / INR and aPTT
by Tori Seasor, M.D., Karen A. Moser, M.D.
Topic summary: Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are common initial tests in the evaluation of patients with suspected bleeding disorders. International normalized ratio (INR) is a calculation allowing for the standardization and comparison of PT clotting time results between laboratories. PT testing can be used clinically for evaluation of bleeding, assessment of liver disease, screening evaluation of factors II, V, VII, X and fibrinogen; aPTT testing can be used clinically for monitoring heparin and certain direct thrombin inhibitor therapy, screening evaluation of factors II, V, VIII, IX, XI, XII, fibrinogen, prekallikrein and HMWK, screening for lupus anticoagulant (lupus sensitive aPTT reagents).

Colon > Noninfectious colitis > Eosinophilic gastroenterocolitis
by Byoung Uk Park, M.D., Lizhi Zhang, M.D.
Topic summary: Eosinophilic gastroenterocolitis (EGEC) is an inflammatory disorder characterized by prominent eosinophilic infiltration of the gastrointestinal tract (stomach, duodenum, small intestine or large intestine) with no known causes of tissue eosinophilia. Overall prevalence of eosinophilic gastroenteritis in the U.S. is 5.1/100,000; more prevalent in the younger population (18 years or younger). Prognostic factors unknown due to the rarity of the disease but observed to be dependent on response to treatment and Klein classification of disease. No established standard treatment guidelines are available; current treatments are based on case reports and case series.

Transfusion medicine > Transfusion therapy > Sickle cell disease
by Yvette C. Tanhehco, Ph.D., M.D., M.S.
Topic summary: A hemoglobinopathy caused by a point mutation in the β globin gene that leads to the production of hemoglobin S, which polymerizes under deoxygenated conditions and causes red blood cells (RBCs) to form a sickle shape. Sickle RBCs are rigid and less deformable, which causes vaso-occlusive pain crises, hemolytic anemia, endothelial injury and inflammation. Pathophysiology: single point mutation (A to T substitution) in the first exon of the β globin gene, converting glutamic acid into valine. Transmission: autosomal recessive gene inheritance pattern. Treatment: RBC transfusions, simple or exchange.

14 January 2022: Weekly Roundup #75


This is what’s new on PathologyOutlines.com:

1. New Editorial Board Appointment for Bone and Soft Tissue Pathology

Dr. Farres Obeidin was appointed to our Editorial Board for Bone and Soft Tissue Pathology. Dr. Obeidin is an Assistant Professor of Pathology at Northwestern University Feinberg School of Medicine. He obtained his M.D. at the Medical College of Georgia and then completed his Anatomic and Clinical Pathology Residency at Northwestern University. He then completed a fellowship in General Surgical Pathology and Bone and Soft Tissue Pathology at the University of California, Los Angeles.

2. 2021 Website Statistics

These pages, accessible by links on the Statistics tab in the Header and Footer, are now updated with 2021 statistics:

3. Worldwide Directory of Pathologists

This is Dr. Pernick’s favorite image. It features a gastric MALT lymphoma and can be found on his Directory page. It illustrates that H. pylori can cause malignancies by the process of antigen driven lymphoproliferation, and we can actually cure at least some malignancies with antibiotics!

What is your favorite image? Email it to us at Directory@PathologyOutlines.com (up to 10MB as an attachment) with a figure legend, diagnosis and subspecialty, and we will add it to your Directory profile. If you don’t have a profile yet and you are a pathologist, sign up by filling in a short form at https://www.surveymonkey.com/r/CMTGNSK.

Currently, we have profiles for ~33% of all U.S. academic pathologists. We should finish adding the rest by this summer (excluding those who opt out). Then, we will start adding other pathologists. That said, any pathologist can sign up now by filling in the short form linked above.

13 January 2022: Textbook Updates

We have posted updates of the following topics:

Adrenal gland & paraganglia > Adrenal cortical carcinoma > Sarcomatoid variant
by Maria Tretiakova, M.D., Ph.D.
Topic summary: Extremely rare malignant tumor of adrenal cortex with biphasic carcinomatous and sarcomatous morphology. Least common variant of adrenal cortical carcinoma (ACC), ~30 cases reported. Slightly more common in females; M:F = 1:1.3. Vast majority presented with localized pain (abdominal pain and distension, loin pain, flank pain, back pain) related to the mass effect. Sarcomatoid ACC has a dismal prognosis, worse than conventional ACC; despite aggressive treatment, overall median survival for sarcomatoid ACC is 7 months. Radical resection is treatment mainstay.

Bone & joints > Other chondrogenic tumors > Periosteal chondroma
by Nuha Shaker, M.D., M.S., Shadi Qasem, M.D., M.B.A.
Topic summary: Rare benign cartilaginous neoplasm that arises on the surface of cortical bone beneath periosteum. Well defined dome shaped lesion. Affects children and young adults, predominantly < 30 years of age. Occurs in small bones of the hands and long bones of the skeleton. A subset of periosteal chondromas harbor mutations in one of the IDH genes. Benign tumor with a reported recurrence rate of 3.6%. Surgical management in the form of intralesional, marginal or en bloc resection, is the mainstay of therapy.

Lymphoma & related disorders > Mature T/NK cell disorders > T follicular helper phenotype > Follicular peripheral T cell lymphoma (F-PTCL)
by Abdallah Flaifel, M.D., Nicholas Ward, M.D.
Topic summary: A rare subtype of nodal lymphomas of T follicular helper (Tfh) cell origin with a follicular or perifollicular growth pattern exhibiting strong and consistent expression of T follicular helper markers. F-PTCL shares with angioimmunoblastic T cell lymphoma (AITL) not only morphologic features but also similar clinical features, genetic landscape and molecular signatures, which may suggest a common pathophysiology. Rare; slightly M > F. Typically aggressive course with reported 50% mortality within 24 months of diagnosis. Distinction between F-PTCL and PTCL, NOS has currently no impact on clinical management.

Soft tissue > General > WHO classification
by Borislav A. Alexiev, M.D.
Topic summary: WHO classification of soft tissue tumors serves as a guide to clarify diagnoses among a multidisciplinary team composed of pathologists, radiologists and clinicians. Adipocytic tumors: new entities atypical spindle cell / pleomorphic lipomatous tumor and myxoid pleomorphic liposarcoma. Fibroblastic and myofibroblastic tumors: 3 new benign entities are considered in the new classification. So called fibrohistiocytic tumors: most relevant entity that has disappeared since 2013 is represented by the family of so called malignant fibrous histiocytoma (MFH).

Stains & CD markers > Actin, alpha smooth muscle type
by Kemal Kösemehmetoğlu, M.D., Gina Johnson, M.D.
Topic summary: Actin is a 43000 kDa ubiquitous protein found in all cells. Identifies pericytes, myoepithelial cells, smooth muscle cells and myofibroblasts in normal, reactive or neoplastic tissue. Also called smooth muscle actin, SMA; clone ASM1 / 1A4 or sm 1. Alpha actins are found in muscle tissues and required for contraction, whereas the beta and gamma actins function as components of the cytoskeleton in many cells. Controversial results on deficiency in intestinal pseudoobstruction. Myogenic differentiation (either only SMA or SMA+ desmin) in dedifferentiated liposarcoma significantly decreases 5 year disease free survival.

12 January 2022: “Ending Cancer As We Know It”

On the 50th anniversary of the National Cancer Act of 1971, we are highlighting videos discussing President Biden’s goal of “ending cancer as we know it”.

First is this video from Dr. Ned Sharpless, Director of the National Cancer Institute:

Our “Curing Cancer Network” group is focused on substantially reducing cancer deaths.

What are your ideas for substantially reducing cancer deaths? Post them in the comments below or email Dr. Pernick at Nat@PathologyOutlines.com.

11 January 2022: Image Quiz #73

Author: Raul S. Gonzalez, M.D.

Which of the following typically causes bland cholestasis as seen on a liver biopsy?

Select an answer:

A. Amoxicillin / clavulanate injury

B. Anabolic steroid injury

C. Chronic large duct obstruction

D. Primary biliary cholangitis

E. Primary sclerosing cholangitis

To sign up for our biweekly image quiz newsletters and more, visit pathologyoutlines.com/subscribe.html.

10 January 2022: Textbook Updates

We have posted updates of the following topics:

Adrenal gland & paraganglia > Adrenal cortical carcinoma > Oncocytic variant
by Maria Tretiakova, M.D., Ph.D.
Topic summary: Malignant epithelial tumor of adrenal cortical cells with predominantly oncocytic morphology. Tend to be lower stage, rarely invade adjacent organs and seem to represent more indolent variant of adrenal cortical carcinoma (ACC) with delayed recurrence and improved survival, despite a larger average size and aggressive morphologic appearance. Median age: 48 years, range: 1 – 83 years; no gender predilection. Pure oncocytic ACC has a better prognosis than conventional ACC. Radical resection is treatment mainstay; lymphadenectomy in 75% of cases.

Kidney tumor > Benign adult tumors > Well differentiated neuroendocrine tumor (carcinoid)
by Lin Cheng, M.D., Ph.D., Maria Tretiakova, M.D., Ph.D.
Topic summary: Well differentiated epithelial neoplasm arising from renal parenchyma and showing neuroendocrine differentiation. Rare tumor arising from renal parenchyma; associated with horseshoe kidney and mature teratoma of kidney. Median age = 59; M:F = 52.2%: 48.8% for all renal neuroendocrine neoplasms. Symptoms include abdominal / back / flank pain, hematuria, palpable mass. Unfavorable prognostic factors: Age: > 40 years; Size: > 4 cm; > 1 mitotic figure/10 high power fields (HPF). Treatment: nephrectomy with lymph node dissection.

Thyroid & parathyroid > Thyroiditis > Subacute thyroiditis
by Truong Phan Xuan Nguyen, M.D., Huy Gia Vuong, M.D., Ph.D.
Topic summary: Granulomatous inflammation of the thyroid gland with characteristic clinical and microscopic findings. Histopathologically, characterized by granulomatous inflammation composed of multinucleated giant cells, foamy and epithelioid histiocytes, neutrophils, lymphocytes and plasma cells. Mostly seen in middle aged women. Diagnosis mainly based on clinical findings (fever, malaise, fatigue, muscle aches, neck pain, thyroid gland tenderness, odynophagia). Self limited, with patients returning to a euthyroid state within a few months. Anti-inflammatory treatment is the key.

Transfusion medicine > Red blood cell antigens > Kidd system
by Brian D. Adkins, M.D., Garrett S. Booth, M.D., M.S.
Topic summary: Antigenic; antibodies clinically significant. Most Kidd antigens are widely expressed in the donor population. Antibodies tend to decrease over time; may become undetectable by blood bank methodology. Can cause hemolytic reactions and hemolytic disease of the fetus and newborn. Antibodies formed tend to be IgG1 or IgG2, which are better at fixing complement; this causes intravascular hemolysis clinically. 2M urea testing can be used to distinguish Kidd positive versus Kidd null individuals; Kidd positive cells will lyse with a rapid influx of urea while Kidd null cells will remain intact.

Vulva, vagina & female urethra > Nontumor > Vulvovaginal cysts
by Morgan Hrones, M.D., Natalia Buza, M.D.
Topic summary: Benign cysts located within the vulva or vagina. Vulvovaginal cysts may be congenital or acquired. Congenitally derived vulvovaginal cysts may represent an embryological derivative, a result of an urological abnormality or ectopic tissue. Müllerian cyst: Comprises 30 – 44% of all vaginal cysts. Gartner duct cyst: most commonly identified vaginal cyst in children. May present as a painful swollen cystic lesion. Most diagnosed clinically by position and appearance. Bartholin duct cyst: complete excision or marsupialization with antibiotic administration if necessary.

7 January 2022: Weekly Roundup #74


This is what’s new on PathologyOutlines.com:

1. New Editorial Board Appointments

Dr. Meaghan Morris was appointed to our Editorial Board for Neuropathology in January of 2022. Dr. Morris is an Assistant Professor of Pathology at Johns Hopkins University. She obtained her M.D. and Ph.D. at Johns Hopkins University, with her graduate studies done in collaboration with the Gladstone Institute of Neurological Disease. She completed her Anatomic Pathology residency and Neuropathology fellowship at Johns Hopkins. 

Dr. Jefree J. Schulte was appointed to the Editorial Board for Thoracic Pathology in December of 2021. He is an Assistant Professor of Pathology at The University of Wisconsin, Madison, where he serves as the faculty lead of the Thoracic, Bone and Soft Tissue subspecialty group and faculty advisor to the histochemistry laboratory. He obtained his M.D. at the University of Illinois College of Medicine and completed his Anatomic and Clinical Pathology residency at The University of Chicago. He subsequently did 2 years of fellowship training in Surgical Pathology at the University of Chicago, focusing on Thoracic, Head and Neck and Gynecologic Pathology.  

2. 2021 – Year in Review Video

We have posted a YouTube video highlighting the significant changes that were made to PathologyOutlines.com in 2021. View it at https://youtu.be/OoLTplgvq0M.

3. Worldwide Directory of Pathologists

Our Pathologist Directory is now approaching 4,000 profiles, including 3,200 US pathologists. Can pathologists find you in the Directory? If not, sign up by completing our short form at https://www.surveymonkey.com/r/CMTGNSK.

The Directory now allows you to combine these search filters: location, subspecialty, institution, last name (first letter).

4. Directory Highlight

This week’s interesting Directory entry is contributed by Peter Wanes, M.D., University of Arizona:

Subspecialty: Cytopathology

Diagnosis: Candida

5. Jobs Page Update

Jobs by subspecialty are now sorted by date posted.

6 January 2022: Textbook Updates

We have posted updates of the following topics:

Adrenal gland & paraganglia > Adrenal cortical carcinoma > Myxoid variant
by Maria Tretiakova, M.D., Ph.D.
Topic summary: Rare variant of malignant epithelial tumor of adrenal cortical cells with extracellular myxoid component. Compared with conventional adrenal cortical carcinoma (ACC), myxoid variant has slightly more aggressive clinical behavior and shorter overall survival on univariate and multivariate analyses. Mean age: 48; age range: 16 – 82. Overexpression of miR-483-3p, miR483-5p and miR-210 indicate poor prognosis and are associated with male sex, presence of necrosis, high Ki67 proliferation index, mitotic count and increased SF1 expression on IHC. Radical resection is treatment mainstay.

CNS tumor > Gliomas, glioneuronal tumors, and neuronal tumors > Diffuse astrocytic and oligodendroglial tumors > Gliosarcoma
by Irfan Yasin, M.B.B.S., Katherine Schwetye, M.D., Ph.D.
Topic summary: Rare, classic variant of glioblastoma (GBM), WHO grade 4. De novo: primary gliosarcoma (GS); secondary GS develops in previously resected or irradiated glioblastoma. Typically affects adults in the fourth to seventh decades of life. Similar genetic alterations (p53 mutations, p16 deletions and PTEN mutations) both in glial and sarcomatous components support monoclonal origin. Median overall survival with treatment (both primary and secondary gliosarcoma): 17.5 months. Treatment includes maximal surgical resection, followed by radiotherapy and chemotherapy.

Placenta > Nonneoplastic placental conditions and abnormalities > Noninfectious > Infarct
by Athena Chen, M.D.
Topic summary: Placental parenchymal lesion comprised of villi that have undergone ischemic necrosis due to focally reduced placental (maternal) blood flow. Increasing number / total percentage of parenchymal involvement and central (versus peripheral / marginal) location are adverse prognostic indicators. Occurs in pregnant women, often whose pregnancies are complicated by gestational hypertension / preeclampsia, intrauterine growth restriction, indicated or spontaneous preterm birth. Severe maternal vascular malperfusion is associated with a 10 – 25% recurrence risk. Specific therapies are not available; however, management / prevention includes optimization of maternal health.

Salivary glands > General > Anatomy & histology
by Theoni Haralabopoulos, M.D., Jonathan Clark, M.B.B.S., Ruta Gupta, M.D.
Topic summary: 3 paired major salivary glands: parotid, submandibular, sublingual. Functional unit of all salivary glands consists of acini and ducts. Developmental process begins when preacinar buds invaginate the adjacent mesenchyme, proliferating through cords, which eventually form clefts and produce extensive branching; end result is terminal bulbs, which form the secretory unit. Saliva has a crucial protective and digestive function within the upper aerodigestive cavity, providing mucosal lubrication and dental protection, facilitating taste, initiating enzymatic digestion of carbohydrates and contributing to oral immunity.

Stains & CD markers > FLI1
by Muhammad Raza, M.B.B.S., Nasir Ud Din, M.B.B.S.
Topic summary: FLI1 (Friend leukemia integration 1) gene is a proto-oncogene located on chromosome 11q24. Due to the increasing number of tumors found to express FLI1, more specific markers or molecular confirmation is necessary for the diagnosis of Ewing sarcoma. Crucial role in maintenance and differentiation of hematopoietic stem cells and angiogenesis. Diagnosis of benign and malignant vascular tumors (positive). Overexpression in astrocytoma = poor prognosis.

4 January 2022: #PathOutPic Twitter Campaign

PathologyOutlines is publicizing the use of the Twitter hashtag #pathoutpic to identify possible histopathology images from Twitter to post in our online textbook. If you tweet high quality histopathology images and are willing to grant us permission to use these images on PathologyOutlines.com, please include the #pathoutpic hashtag in your tweet.

Every few weeks, our image representative will search Twitter for posts with this hashtag. The image representative will select the best images based on image quality (good focus, white balance, visually interesting, etc.), appropriate and reasonable associated text (i.e. the tweet) and whether the image is useful for the appropriate topic(s). This decision is solely within the discretion of the image representative. Not all images with the hashtag will be selected. We will only consider hashtags on the original tweets; users cannot give permission for images they do not own.

In general, images will be posted in the appropriate topic under a header that states “Contributed by @[username] on Twitter” with the diagnosis as the image caption and the Twitter post as the image legend. A URL link to the Twitter post will be included. We may also retweet the original posts with the selected image.

We give permission to the image owner to use the image in other publications, as long as this does not restrict the use of the image on our website. If users post an image with the hashtag but later wish to revoke permission for our site to post the image, they may contact us separately.

3 January 2022: Textbook Updates

We have posted updates of the following topics:

Bladder, ureter & renal pelvis > Urothelial carcinoma – invasive > Plasmacytoid
by Timothy Isaac Miller, M.D., M.A., Maria Tretiakova, M.D., Ph.D.
Topic summary: Aggressive variant of urothelial carcinoma (UC) characterized by single infiltrating cells with eccentrically placed nuclei and abundant eosinophilic cytoplasm similar to plasmacytes or resembling signet ring cells due to intracytoplasmic vacuoles. Uncommon histologic variant of UC (~1 – 3%) with plasmacytoid morphology. Epidemiology same as conventional urothelial carcinoma: typically older men (median of 58 – 68 years) with smoking history association. Overall uniformly poor prognosis. More likely to receive neoadjuvant chemotherapy compared with conventional UC because it is discovered at a higher stage.

Bone marrow neoplastic > Bone marrow – neoplastic myeloid > Miscellaneous > Idiopathic hypereosinophilic syndrome
by Alexander Reese, D.O., Ling Zhang, M.D., Lynh Nguyen, M.D.
Topic summary: Idiopathic hypereosinophilic syndrome is a disorder defined by peripheral blood eosinophilia (absolute eosinophil count ≥ 1.5 x 109/L) for at least 6 months with organ damage / dysfunction attributable to tissue hypereosinophilic infiltrate per biopsy and no discernible underlying etiology. Clinically, if treatment is necessary to minimize tissue / organ damage, the criteria of 6 months might not be enforced and an eosinophil count ≥ 1.5 x 109/L on 2 occasions for ≥ 1 month apart may be sufficient. Typically occurs in adults age 20 – 50 years. Slowly progressive clinical course with death occurring due to cardiac damage in some cases. As HES progresses, initial treatment is often systemic glucocorticoid therapy with second line treatments including imatinib, interferon alfa and hydroxyurea.

Bone marrow nonneoplastic > Benign changes > Megaloblastic anemia
by Swati Bhardwaj, M.B.B.S., M.D., Julie Feldstein, M.D.
Topic summary: Disorder of impaired DNA synthesis (with normal RNA synthesis) that manifests with the presence of megaloblasts in the bone marrow resulting in ineffective and abnormal erythropoiesis and macrocytes / macroovalocytes in the peripheral blood. Multitude of etiologies: most commonly vitamin B12 or folate deficiency. Insufficient data regarding incidence and prevalence. Treatment: supplementation of B12 and folate; when malabsorption is a cause, parenteral supplementation is needed.

Fallopian tubes & broad ligament > Broad ligament > Walthard cell nests
by Shabnam Zarei, M.D.
Topic summary: Nests, cysts or plaques of metaplastic transitional epithelium involving the serosal surface of fallopian tube. Benign incidental finding. Small 1 – 2 mm yellow-white nodules beneath the serosa of the fallopian tube and paratubal soft tissue. Suggested association between Walthard cell nests and Brenner tumors or mucinous tumors of the ovary (stronger association with the former, though unexplained). Walthard cell nests can be the origin for rare examples of Brenner tumors outside the ovarian parenchyma.

Ovary > Other nonneoplastic > Calcification
by Aurelia Busca, M.D., Ph.D., Carlos Parra-Herran, M.D.
Topic summary: Ovarian calcifications are commonly found in the context of a neoplasm (mature teratoma, mucinous cystadenoma, serous neoplasia, etc.) or as incidental findings in grossly normal ovaries. Calcifications are divided into psammomatous (psammoma bodies) and nonpsammomatous. In a study of 28 patients, the presence of large ovarian calcifications (> 5 mm) identified by imaging in otherwise normal ovaries remained stable and was not associated with ovarian neoplasms. Resection if symptomatic, rupture or suspicion for neoplastic process.