8 August 2022: Textbook Updates

We have posted updates of the following topics:

Anus & perianal area > Other nonneoplastic > Fistula
by Fahire Goknur Akarca, M.D., Nikka Khorsandi, M.D., Kwun Wah Wen, M.D., Ph.D.
Topic summary: Anal fistulas are epithelialized tracts created between an external opening in the perianal skin and an internal opening in the anal canal. Benign epithelialized communication between anal canal and perianal skin that is most commonly idiopathic. Mean age of occurrence is 40 years with a range of 20 – 60 years. Most commonly identified causes of anal fistulas are Crohn’s disease, infections and rectal foreign bodies. Treatment: exam under anesthesia is the most common first step of a suspected fistula, to determine complexity and characteristics. Simple fistula is treated with a primary fistulotomy with incision made along fistula tract for curettage and to promote adequate tract drainage and wound healing; this is very curative.

CNS & pituitary tumors > Gliomas, glioneuronal tumors, and neuronal tumors Adult-type diffuse gliomas > Astrocytoma, IDH mutant
by John DeWitt, M.D., Ph.D.
Topic summary: IDH1 / IDH2 mutated, diffusely infiltrating glioma, most often with concurrent TP53 or ATRX mutations and without 1p / 19q codeletion. In the absence of 1p / 19q codeletion, a component that morphologically resembles oligodendroglioma is compatible with this diagnosis. Age of diagnosis is typically younger than glioblastoma, IDH wild type, with higher grade tumors occurring more often in older patients (third or fourth decade for grade 2 or 3, versus fifth decade for grade 4). Within IDH mutant astrocytoma, younger age is correlated with improved prognosis and survival. Complete resection as extensively as is safely possible.

Oral cavity & oropharynx > Soft tissue tumors & proliferations > Parulis
by Molly Housley Smith, D.M.D.
Topic summary: Localized collection of acute inflammation and edematous granulation tissue on the gingiva, which represents the intraoral opening of a draining odontogenic (dental) infection. Diagnosis is most often made upon clinical evaluation of fluctuant / draining gingival nodule associated with adjacent dental infection; histopathologic confirmation is useful but may not be needed. Parulides may be accompanied by an ill or well defined radiolucency at or around the apex of a nonvital tooth. While the gingival nodule may be removed surgically, the nodule will recur without effective treatment of the underlying associated infection (e.g., root canal therapy, dental extraction, etc.).

Stomach > Neuroendocrine tumors > Well differentiated neuroendocrine tumor
by Dana Razzano, M.D., Teri A. Longacre, M.D.
Topic summary: The 5th edition of the WHO 2019 Digestive Tumors Classification definition of neuroendocrine tumor (NET): well differentiated, grade 1, 2 or 3 based on mitotic rate per 2 mm2 (based on counting 10 mm2 and taking the average) and Ki67 immunohistochemical index (counted in ≥ 500 cells in the area of highest staining); grade assigned by whichever value is higher. Type I is the most common, followed by type III, with type II being very rare. All types tend to occur in the age range of 50 – 60 years. Prognostic factors: dependent on tumor subtype, grade and stage at presentation. Treatment: dependent on size at time of endoscopic evaluation.

5 August 2022: Use of Author Contributed Images

We appreciate all the authors who have contributed images to topics at PathologyOutlines.com. In general, these images are protected by our copyright and cannot be used by others (except for the contributors) without our consent. However, they typically can be used for limited educational purposes under the Fair Use doctrine without consent (see https://libguides.unm.edu/images/fairuse).

Recently, several organizations, both nonprofits and businesses, have requested permission to use some of our images. We may allow this after review, but typically we require that they attribute the image to the submitter and to us. For business use, if a large number of images are requested, we charge the business a fee solely to cover our administrative costs (i.e., we do not pay the author).

If you have any questions about using our images, please email comments@pathologyoutlines.com.

4 August 2022: Textbook Updates

We have posted updates of the following topics:

CNS & pituitary tumors > Meningeal tumors > Anaplastic meningioma
by Valeria Barresi, M.D., Ph.D.
Topic summary: WHO 2021 definition: a meningioma with overtly malignant cytomorphology that can resemble a carcinoma, melanoma or high grade sarcoma, display markedly elevated mitotic activity, harbor a TERT promoter mutation or have homozygous CDKN2A / CDKN2B deletion. Occurs at any age, mainly adults 45 – 85 years. Sites: cerebral or spinal meninges; cerebral ventricles. Favorable prognostic factors: age 20 – 44 years and spinal location. Treatment: surgery followed by fractioned radiotherapy, experimental chemotherapy or peptide receptor radionuclide therapy.

Colon > Polyps > Inflammatory fibroid polyp
by M.J. Fernández-Aceñero, M.D., Ph.D.
Topic summary: Rare mesenchymal polypoid neoplasms that arise anywhere throughout the GI tract but most commonly in the stomach and small intestine. Rare in the large bowel. Predominance in middle aged adults (median 53 years), with wide variation (4 – 84 years). Discovery of overexpression and mutations in platelet derived growth factor receptor alpha (PDGFRA) has led to considering inflammatory fibroid polyp a neoplastic process. Good prognosis with no risk of malignization. Endoscopic resection is the preferred option, either polypectomy or endoscopic submucosal or radical resection.

Esophagus > General > Grossing & features to report
by Israh Akhtar, M.D.
Topic summary: This topic describes how to gross esophageal biopsies, esophagectomy specimens and endoscopic mucosal resection specimens. Location of biopsies: upper (cervical), middle (midthoracic) or lower esophagus (lower thoracic). Esophagectomies are performed with or without proximal stomach for severe dysplasia or for neoplasms; less frequently for strictures. If no gross tumor present (which is often the case after neoadjuvant therapy of the GE junction tumors), then the entire ulcerated / fibrotic area should be blocked off and submitted.

Pancreas > Neuroendocrine neoplasms > Neuroendocrine carcinoma
by Maria Gaia Mastrosimini, M.D., Claudio Luchini, M.D., Ph.D.
Topic summary: Poorly differentiated, high grade, malignant epithelial neoplasm with neuroendocrine differentiation. By morphology, PanNECs can be divided into small cell or large cell subtypes. Mean patient age is 59 years (patients are usually aged 50 – 60 years but can occur in younger patients as well). Very poor prognosis, compared to WD PanNETs; metastatic spread is present in most patients at the time of diagnosis. Treatment: surgical resection; chemotherapy (no established protocol) – platinum based regimen.

Soft tissue > Fibroblastic / myofibroblastic > Proliferative fasciitis
by Laura Warmke, M.D., Jeanne Meis, M.D.
Topic summary: Proliferative fasciitis is a pseudosarcomatous proliferation of myofibroblastic / fibroblastic cells with large ganglion-like cells involving subcutaneous tissue. Variable collagenous to myxoid stroma. Occurs predominantly in middle aged adults (mean age: 51 years). Subset of cases has a recurrent FOS gene rearrangement. Benign clinical course; usually self limited, disappearing within 1 – 12 weeks. Adequately treated by simple / conservative local excision.

2 August 2022: Worldwide Directory of Pathologists Update

We have now created a list of all pathologists at academic institutions in the U.S. and Canada for entry into the Directory. We currently have 7,000+ U.S. profiles, 750+ Canadian profiles (mostly academic) and we estimate that U.S. and Canadian academic pathologists will total ~10,000 when all profiles are created, targeted for October 2022.

Pathologists are defined for the Directory as having a doctoral degree plus pathology residency or fellowship training (or comparable); this includes PhDs and other subspecialists. Typically, they perform or can perform direct patient care at the level of an AP or CP attending. We include residents and fellows in the Directory, but not medical students.

We also include pathologists who are now doing something else as well as deceased pathologists already in the Directory for 5 years after passing. We are able to inactivate Directory entries if a pathologist requests for their profile to be removed.

See the blue box on the Directory page to learn how to add or update your profile. We plan to add a Consultation search in the fall of 2022, so you may want to review your profile to make sure it is as accurate as possible.

1 August 2022: Textbook Updates

We have posted updates of the following topics:

CNS & pituitary tumors > Gliomas, glioneuronal tumors, and neuronal tumors > Adult-type diffuse gliomas (topics to be merged) > Glioblastoma, IDH wild type
by Bharat Ramlal, M.D., Meaghan Morris, M.D., Ph.D.
Topic summary: An aggressive, infiltrating, astrocytic glioma that lacks mutations in IDH1, IDH2 and histone H3 genes. Characterized by diffusely infiltrative growth pattern with nuclear atypia and either histologically defined by brisk mitotic activity and microvascular proliferation or necrosis, or molecularly defined by the presence of TERT promoter mutation, EGFR amplification or combined gain of chromosome 7 and loss of chromosome 10. Poor prognosis, with a median survival of 8 months and 5 year survival rate of only 6.8%. Surgical resection where possible in younger patients (≤ 70 years old) and patients with good performance status, followed by radiotherapy with concurrent and adjuvant temozolomide (TMZ).

Lymph nodes & spleen, nonlymphoma > Lymph nodes-inflammatory / reactive disorders > Castleman disease
by Jayalakshmi Venkateswaran, M.D., Jayalakshmi Balakrishna, M.D.
Topic summary: Unusual heterogeneous group of lymphoproliferative disorders with some common morphological features involving lymph nodes or extranodal sites. 3 distinct clinical entities: unicentric Castleman disease (UCD), multicentric Castleman disease (MCD) and oligocentric or regional Castleman disease. UCD can affect all age groups and shows no gender difference with the median age of onset in the fourth decade. MCD affects patients of all ages with a median age of onset in the fifth to seventh decades. UCD: localized and excellent response to therapy. MCD: poorer prognosis, especially HIV positive patients and patients with MCD POEMS.

Ovary > Endometrioid tumors > Endometrioid cystadenoma / adenofibroma
by Stephanie L. Skala, M.D.
Topic summary: Benign tumors with endometrioid type glands, sometimes associated with endometriosis. Squamous or mucinous metaplasia or dystrophic stromal calcifications can be seen. In some cases, endometrioid cystadenomas may represent endometriotic cysts without obvious endometrial type stroma. Uncommon tumors, most often seen in postmenopausal women. Detected on pelvic imaging (ultrasound, CT, MRI). Symptoms may include abnormal vaginal bleeding, abdominal pain or pelvic mass. Treatment: not applicable; these tumors are benign.

Skin melanocytic tumor > Nevi > Dysplastic nevus
by Sepideh Nikki Asadbeigi, M.D., Cuong Nguyen, M.D.
Topic summary: Pigmented lesions that share clinical and histological features of both common nevi and melanoma. Although many melanomas arise de novo (without an obvious or detectable precursor lesion), approximately 25% histologically demonstrate an associated melanocytic nevi. Higher incidence among patients with history of melanoma. Diagnosis is heavily dependent on the histologic features and has a relatively poor interobserver correlation. Most dysplastic nevi never progress to melanomas even though they are associated with melanomas. Treatment: sun protection. Re-excision: decision to re-excise depends on the clinician’s perception and risk assessment.

Stains & CD markers > Tpit
by William McDonald, M.D.
Topic summary: Pituitary adenoma / pituitary neuroendocrine tumor has traditionally been classified using a combination of immunohistochemical stains for anterior pituitary hormones, including stains for prolactin, growth hormone, thyrotropin (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), adrenocorticotropic hormone (ACTH) and the alpha subunit (ASU) of the glycoprotein hormones. Tpit is expressed within anterior pituitary gland corticotroph cells and within corticotroph adenomas. Nuclear expression is evaluated (reactivity only in the cytoplasm is regarded as negative). Untreated Cushing disease has high morbidity and mortality, with surgery being the treatment of choice for small, functioning corticotroph adenomas.

28 July 2022: Textbook Updates

We have posted updates of the following topics:

Bone & joints > Chondrosarcoma > Atypical cartilaginous tumor
by Serenella Serinelli, M.D., Ph.D., Gustavo de la Roza, M.D.
Topic summary: Low grade, locally aggressive, hyaline cartilage producing tumor arising in the appendicular skeleton. Microscopically identical to grade 1 chondrosarcoma (which arises in the axial skeleton). Third to sixth decades of life; M = F. Sporadic: 90% of cases; somatic mutations in the isocitrate dehydrogenase genes IDH1 / IDH2 in 50% of tumors, leading to altered hydroxyglutarate levels. Treatment: intralesional excision with curettage, adjunctive high speed burring and bone void augmentation. Atypical cartilaginous tumors show good prognosis, after curettage.

Bone marrow nonneoplastic > Infectious / inflammatory > Granulomatous inflammation
by Yulan Jin, M.D., Ph.D., Ling Zhang, M.D.
Topic summary: Granuloma is formed by aggregates of histiocytes / macrophages, admixed with variable inflammatory cells, with or without giant cells. Underlying etiologies include infections, sarcoidosis, hematologic and nonhematologic malignancies, drug reaction, autoimmune diseases and other disorders. Broad age range, mainly aged > 40 years; slight male predominance. Good prognosis for those caused by drug reaction (e.g., BCGitis) and for those without definitive underlying causes. Treatment varies for specific underlying causes.

Breast > Other benign tumors > Hemangioma
by Indu Agarwal, M.D., Luis Blanco, Jr., M.D.
Topic summary: Benign vascular lesions, microscopically well circumscribed and lacking endothelial cell atypia; origination from large nonneoplastic “feeding” vessels, may be seen at the periphery of the lesion. Proliferation of well differentiated vessels of varying sizes. Reported in all ages, range 18 months to 82 years. Prognostic factors: can recur; no metastasis reported. Excision has been done in the past; excision may not be mandatory if radiological / pathologic correlation is available.

Skin nonmelanocytic tumor > Benign (nonmelanotic) epidermal tumors or tumor-like lesions > Inverted follicular keratosis
by Said Albahra, M.D., Gregory A. Hosler, M.D., Ph.D.
Topic summary: Benign tumor of the follicular infundibulum. Benign, endophytic follicular tumor with characteristic presence of squamous eddies. Solitary flesh colored nodular or filiform lesion. More common in males and older individuals. Most commonly on the head and neck (~90% of cases) but can also be found on extremities or trunk. Diagnosis can be made on biopsy. Treatment: biopsy is usually curative; larger lesions treated by complete excision.

Soft tissue > Fibroblastic / myofibroblastic > Fibrous hamartoma of infancy
by Muhammad Raza, M.B.B.S., Madiha Bilal Qureshi, M.B.B.S., Nasir Ud Din, M.B.B.S.
Topic summary: A benign soft tissue neoplasm of infants and young children, showing organoid, triphasic morphology with bundles of bland fibroblastic / myofibroblastic cells, nodules of primitive, rounded or stellate cells with myxoid stroma and mature adipose tissue. Very rare; mean age at diagnosis: 15 months (range: birth to 14 years); 20% are congenital. Commonly involves the axilla, trunk, upper extremities and genital regions. Cured with local excision.

26 July 2022: Image Quiz #87

Authors: Christopher Dall, M.D.Debra L. Zynger, M.D.

Teratoma with somatic type malignancy most commonly contains which histologic type?

Select an answer:

A. Adenocarcinoma

B. Primitive neuroectodermal tumor

C. Rhabdomyosarcoma

D. Sarcoma, not otherwise specified

E. Squamous cell carcinoma

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

25 July 2022: Textbook Updates

We have posted updates of the following topics:

Bladder, ureter & renal pelvis > Other nonneoplastic > Intestinal metaplasia
by Rugvedita Parakh, M.D.
Topic summary: Replacement of urothelium by benign colonic or small intestinal epithelium, with presence of mucin producing goblet cells. May coexist with cystitis glandularis, characterized by formation of glandular structures in lamina propria within von Brunn nests that have an innermost lining of columnar or cuboidal cells bound by transitional cells at periphery. Incidence increases with age; mean age of diagnosis 57 years (range 23 – 81 years). Long term follow up of intestinal metaplasia has confirmed a benign behavior. Treatment: May regress completely if pathogenic factor is removed.

Bone & joints > Osteomyelitis > Chronic osteomyelitis
by Mohammad Khurram Minhas, M.B.B.S., Nasir Ud Din, M.B.B.S.
Topic summary: Longstanding infection of bone lasting months to years; characterized by low grade inflammation and presence of dead bone or fistulous tract. Most common organism: Staphylococcus aureus; responsible for 80 – 90% of cases. Incidence is highest in adults, 41 – 50 years (29%); attributed partly to higher frequency of traumatic injury in this population. Diabetes is a poor prognostic factor in patients with chronic osteomyelitis; poor prognosis in patients with nutritional and systemic diseases. Treatment: antibiotic therapy; surgical therapy (debridement, saucerization, sequestrectomy, continuous intramedullary irrigation); may require myocutaneous flaps.

Chemistry, toxicology & urinalysis > Urine & renal function > Urine crystals & microscopy
by Archana Shetty, M.B.B.S., M.D.
Topic summary: Standard component of complete urinalysis. Urine analysis is the third major diagnostic screening test in the clinical laboratory, only preceded by serum / plasma chemistry profiles and complete blood count analysis. Indications for testing: helps diagnose kidney disease; urinary tract infection; cancers of urinary tract; reactions to medicines; prostate infection; liver disease; yeast, viral, parasitic infections. Automated urine analyzers enhance productivity and turnover in the laboratories by increasing the reproducibility and productivity / throughput. Urine reagent strips: analytes detected can be ascorbic acid, glucose, bilirubin, ketone (acetoacetic acid), specific gravity, blood, pH, protein, urobilinogen, nitrite and leukocytes.

Lymphoma & related disorders > Hodgkin lymphoma > CHL lymphocyte depleted
by Anna B. Owczarczyk, M.D., Ph.D., Lauren Smith, M.D.
Topic summary: Subtype of classic Hodgkin lymphoma (CHL) with numerous Reed-Sternberg cells and scant nonneoplastic background lymphocytes. Median age 30 – 40 years; male predominance. Predilection for subdiaphragmatic region (retroperitoneal lymph nodes, abdominal organs) and bone marrow. Unfavorable prognostic factors: advanced disease stage, advanced age, presence of B symptoms, 3 or more lymph node areas involved, large mediastinal mass, high ESR (erythrocyte sedimentation rate), HIV positive. Standard therapy: ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) with or without localized radiotherapy.

22 July 2022: Weekly Roundup #94

What’s new on PathologyOutlines.com this week?

1. Tip of the Month – July 2022

We have posted a YouTube video highlighting the July 2022 PathologyOutlines.com Tip of the Month. View it at https://youtu.be/O3dMN4QqoGU.

2. Author Recruitment

We continue to look for academics who meet our author qualifications. If interested, email Nat@PathologyOutlines.com with your CV and areas of interest.

3. Senior Authors

We have removed the position of Senior Author from our topics, which we have not used for several years. Although at least 1 member of the author team must meet our author qualifications, we are no longer making a distinction on the website between the authors.

4. Tracking / Cookies

We are investigating the use of tracking software that does not collect any information about you (i.e., no cookies). While we do have to track basic statistics (page views, visits, clicks) in order to function, we want to maintain your privacy and keep the site as user friendly as possible. We will keep you advised.

21 July 2022: Textbook Updates

We have posted updates of the following topics:

Autopsy & forensics > Types of injuries > Asphyxia
by Lorenzo Gitto, M.D., Ponni Arunkumar, M.D.
Topic summary: Asphyxia: generic term that indicates a condition resulting from an interference with respiration due to the lack of oxygen in the air or in the blood, a failure of cells to utilize oxygen or a failure of the body to eliminate carbon dioxide. Types of asphyxia: suffocation (smothering, choking, confined space and vitiated atmosphere), strangulation (hanging, manual strangulation, ligature strangulation), mechanical (positional, compression), drowning, special types (autoerotic, incaprettamento, judicial hanging, mass suicide hanging). Autopsy findings: neck injuries may be observed in asphyxias with neck compression mechanisms.

Kidney nontumor > Glomerular disease > Fibrillar disease > Renal amyloidosis
by Anthony Sisk, D.O.
Topic summary: A group of insoluble proteins organized into beta pleated sheets, which deposit within extracellular spaces of a variety of tissues leading to organ dysfunction and disease. Immunofluorescence and immunohistochemistry findings can be helpful in determining amyloid type. Epidemiology, etiology, clinical features are dependent on the amyloid type. Unfavorable prognostic factors: dialysis requirement, massive proteinuria, renal failure at presentation, severe hypoalbuminemia, coexisting multiple myeloma, heavy organ involvement, IgM related monoclonal protein. Treatment based on amyloid type, underlying cause of disease and symptoms.

Kidney nontumor > Tubulointerstitial disease > Ischemic injury > Acute tubular necrosis
by Dale Davis, M.D., M.A., Astrid Weins, M.D., Ph.D.
Topic summary: Sudden decline in renal function, secondary to ischemic or toxic damage to renal tubular epithelial cells. Clinically similar to acute interstitial nephritis (AIN); histopathology needed for diagnosis. True ATN presents in 1% of hospitalized patients and ~4/10,000 of the general population; more likely to affect patients with comorbidities. Prognosis favorable unless sustained renal failure or combined with systemic issues or other underlying conditions. Underlying cause will determine route of treatment.

Laboratory Administration & Management of Pathology Practices > Qualifying board topics > Inspection and accreditation processes > Laboratory inspection and accreditation
by Mai Thy Tran, M.D., Lewis A. Hassell, M.D.
Topic summary: Laboratory accreditation refers to a stamp of approval granted to a laboratory by an external entity, intended to assure quality of processes and personnel; it generally indicates that the lab meets the standards established by the accrediting agency. Standards of performance and operation are specified by the accrediting agency. Benefits: demonstrates competence of the laboratory; assists lab employees in learning, developing a sense of pride in their work and in maintaining high standards; a tool to recognize laboratories worldwide.

Molecular markers > CSF3R
by Yan Chen Wongworawat, M.D., Ph.D., Kevin E. Fisher, M.D., Ph.D.
Topic summary: Colony stimulating factor 3 receptor. Somatic activating mutations in CSF3R are the most frequent molecular alteration in patients with chronic neutrophilic leukemia (CNL), seen in > 60% of cases. Activating mutations in CSF3R localize to 2 distinct protein domains. Inherited / germline mutations in this gene are associated with autosomal dominant hereditary neutrophilia and autosomal recessive severe congenital neutropenia 7. Coexistence of CSF3R and ASXL1 mutations is associated with a poorer prognosis in CNL.