21 January 2021: Textbook Updates

We have posted updates of the following topics:

Bone marrow neoplastic > Bone marrow – neoplastic myeloid > Recurrent genetic abnormalities > AML with inv(16)(p13.1;q22) or t(16;16)(p13.1;q22)
by Shuchi Zinzuwadia, B.S., Angeli Mittal, M.D., Maryam F. Raouf, M.D., Rita Gupta, M.D. , Ameet R. Kini, M.D., Ph.D.
Topic summary: Inv(16)(p13.1;q22) or t(16;16)(p13.1;q22) results in the formation of an abnormal core binding factor beta subunit / myosin heavy chain 11 (CBFB-MYH11) fusion gene. Most cases show myelomonocytic differentiation with presence of abnormal eosinophils. 7% of AMLs in the pediatric age group. Most cases present with involvement of the blood and bone marrow. Diagnosis is based on a combination of morphology, flow cytometry, conventional cytogenetics, real time PCR and FISH analysis. Treatment involves induction chemotherapy with 3 days of anthracycline and 7 days of cytarabine (7+3). Overall prognosis is good compared to other AMLs.

Cervix > General > WHO classification
by Carlos Parra-Herran, M.D.
Topic summary: Updated classification of tumors of the cervix as per the World Health Organization classification of tumors of female reproductive organs, 5th edition (2020). Preinvasive glandular lesions, as well as invasive squamous and glandular lesions, are now classified in 2 main categories: HPV associated and HPV independent. HPV independent squamous cell carcinomas are rare but are included since they may be more aggressive than the more common HPV associated lesions. HPV associated adenocarcinomas can be classified using terminology from previous classification; however, they need to be distinguished from HPV independent tumors. HPV independent adenocarcinomas are most frequently of the gastric type; other distinct types include clear cell and mesonephric.

Oral cavity & oropharynx > Oropharynx squamous cell carcinoma > HPV negative
by Katherine Hulme, M.B.Ch.B., Ruta Gupta, M.B.B.S., M.D.
Topic summary: A subset of oropharyngeal squamous cell carcinomas that are not associated with high risk human papillomaviruses (HPV). Oropharynx includes the soft palate, uvula, palatine tonsils, posterior third (base) of the tongue and posterior wall of the pharynx. Mean age 61 years. Invasive lesion is typically preceded by progressively severe dysplasia. Most commonly caused by chewing or smoking tobacco, heavy alcohol use and poor oral hygiene. Diagnosis is based on clinical examination with biopsy of primary lesion. Treatment involves surgical resection of the primary along with ipsilateral or bilateral elective neck dissection. Adjuvant radiotherapy and platinum based chemotherapy.

Oral cavity & oropharynx > Potentially malignant & dysplasia > Leukoplakia
by Ivan J. Stojanov, D.M.D., M.M.Sc.
Topic summary: Hyperkeratotic (white) plaque / patch of mucosa exhibiting clonality and representing precursor lesion to squamous cell carcinoma. Approximately 40% of leukoplakias exhibit keratinizing dysplasia; the remainder are characterized by hyperkeratosis alone. Worldwide prevalence approximately 0.5%. Associated with smoking / smokeless tobacco, alcohol and areca nut (betel quid) use. Biopsy required for diagnosis and risk stratification. Surgical excision results in 3 times reduction in risk of malignant transformation. Close clinical observation may be appropriate for extensive leukoplakia or patients with comorbidities.

Salivary glands > Primary salivary gland neoplasms > Benign > Sclerosing polycystic adenoma
by Kim A. Ely, M.D.
Topic summary: Rare salivary gland disorder, first described in 1996. Resembles fibrocystic changes and sclerosing adenosis of the breast. Occurs over a wide age range (9 – 84 years); mean: 40 years. Occurs in the parotid gland (around 70%), occasional examples in the submandibular glands and oral cavity. Originally believed to be a reactive, nonneoplastic process resembling fibrocystic changes of the breast but evidence suggests it is likely neoplastic. Slow growing mass, may have pain or altered sensation. Diagnosis best made on histologic examination of excisional material. Treatment involves complete, conservative local resection followed by prolonged surveillance.

18 January 2021: Textbook Updates

We have posted updates of the following topics:

Bladder, ureter & renal pelvis > General > Staging-bladder carcinoma
by Debra L. Zynger, M.D.
Topic summary: All carcinomas of the bladder are covered by this staging system. These topics are not covered: urachal carcinoma, paraganglioma, sarcoma or lymphoma. Lamina propria (pT1) contains connective tissues between urothelium and detrusor muscle (muscularis propria), made of loose stroma, variably sized blood vessels and thin muscle bands of muscularis mucosae. Muscularis propria (pT2) is thick aggregated muscle bundles of detrusor muscle; must distinguish from hypertrophic muscularis mucosae. Perivesical adipose tissue (pT3) is deep to muscularis propria but is also present within deep lamina propria, usually as small localized aggregates and within muscularis propria (superficial and deep). If carcinoma of the bladder transmurally invades through the bladder wall and into the prostatic stroma, the tumor is designated as pT4a.

Bone marrow neoplastic > Bone marrow – neoplastic myeloid > AML not otherwise specified > Acute basophilic leukemia
by Pallavi Khattar, M.D., Puneet Bedi, M.D., Mariko Yabe, M.D., Ph.D.
Topic summary: First described (basophilic leukemia) in 1906 by Joachim; acute myeloid leukemia (AML) with primary differentiation to basophils. First step in diagnosis is the recognition of the presence of coarse basophilic granules. Rare disease; ~ 4 – 5% of all cases of acute nonlymphocytic leukemia and 36 months in chronic basophilic leukemia. Treatment involves stem cell transplant (SCT). If SCT is not possible, polychemotherapy, targeted drugs, experimental drugs or palliative cytoreductive treatment.

Lymphoma & related disorders > Mature B cell neoplasms > DLBCL and large B cell lymphomas with high grade features > High grade B cell lymphoma, NOS
by Mark G. Evans, M.D., Jon C. Aster, M.D., Ph.D., Roberto N. Miranda, M.D., L. Jeffrey Medeiros, M.D.
Topic summary: Newly defined high grade B cell lymphoma in the revised 2016 WHO. Heterogenous category of aggressive mature B cell lymphomas that may be transformed or arise de novo. Rare; true frequency is unknown but increases with age. Few studies have been conducted but this lymphoma may arise from germinal center B cells in 20 – 35% of cases with MYC rearrangement and amplification / gain of BCL2. Morphological evaluation reveals cells that more likely resemble BL than DLBCL. Advanced stage (stage III – IV) is most common, including involvement of bone marrow and central nervous system. No standardized treatment exists.

Stains & molecular markers > PDL1 22C3
by Gary Tozbikian, M.D.
Topic summary: Programmed death ligand 1 (PDL1) is an immune checkpoint protein expressed on activated immune cells and tumor cells. Alternative names: PDCD1 ligand 1, PDCD1L1, cluster of differentiation 274 (CD274), B7 homolog 1 (B7-H1), pharmDX PD-L1 (22C3). Normally expressed on activated immune cells (e.g. antigen presenting cells and B cells). Current companion diagnostic indications for PDL1 (22C3) include non small cell lung carcinoma (NSCLC), cervical carcinoma (including cervical squamous cell carcinoma and endocervical adenocarcinoma), urothelial carcinoma, head and neck squamous cell carcinoma (HNSCC), gastric / gastroesophageal junction adenocarcinoma, advanced / metastatic triple negative breast cancer (TNBC).

14 January 2021: Textbook Updates

We have posted updates of the following topics:

Autopsy & forensics > Types of injuries > Gunshot wounds
by Lorenzo Gitto, M.D., Robert Stoppacher, M.D.
Topic summary: Gunshot wounds occur when a bullet hits the body, producing injuries. Determining the range of fire is one of the most critical parts of the forensic pathologist activity; secondary effects of the discharge surrounding the entrance wound (muzzle imprint, soot deposition, stippling or blackening of the skin edges) can help estimate the firing range. Types of gunshot wounds include penetrating wounds, perforating wounds, re-entry wounds and graze / tangential wounds. At autopsy, it is essential to provide proper documentation (by photographs and body diagrams) of the gunshot wound’s features.

Breast > Inflammatory > Acute mastitis / abscess
by Kristen E. Muller, D.O.
Topic summary: Infection or inflammation of breast tissue, usually bacterial, often seen in association with lactation. If untreated, may form abscess and fistulous tracts; Staphylococcus aureus most common organism. Incidence in 2 – 33% of lactating women. Biopsy may be warranted for suspected abscess, atypical presentation, recurrent infection or treatment failure; Gram stain and culture (aerobic and anaerobic) with sensitivities to guide antibiotic selection (rarely needed). Recurrent breast abscesses are more likely to be smokers and have mixed bacterial and anaerobic infections. Symptomatic treatment: effective milk removal via breastfeeding, pumping or hand expressing to fully empty breasts, analgesia, warm compress.

Stains & molecular markers > Prostate specific antigen (PSA)
by Heather I-Hsuan Chen-Yost, M.D., Tatjana Antic, M.D.
Topic summary: Androgen regulated serine protease; encoded by kallikrein gene (KLK3, kallikrein related peptidase 3) located on chromosome 19. A cytoplasmic marker that is sensitive and specific for prostatic tissue and adenocarcinoma of prostatic origin. Produced by the secretory cells of prostatic ducts and acini in males and Skene glands in females. Cytoplasmic staining (positive expression is strong, granular, diffuse). Reduced or negative expression in poorly differentiated prostate cancers linked to unfavorable tumor phenotype and poor prognosis.

Thyroid gland > Papillary thyroid carcinoma > Rare variants > Fibromatosis / fasciitis-like
by Shipra Agarwal, M.D.
Topic summary: Rare histological variant of papillary thyroid carcinoma (PTC) characterized by an abundant stroma resembling nodular fasciitis / fibromatosis / other myofibroblastic proliferative processes. Prominent myofibroblastic proliferation histomorphologically similar to fibromatosis or nodular fasciitis of soft tissue. Exceedingly rare, with less than 50 well documented cases reported. Diagnostic workup is similar to any thyroid mass / nodule. Prognosis similar to classic PTC of similar size and stage. Treatment, based on American Thyroid Association and NCCN guidelines, is usually surgical excision.

11 January 2021: Textbook Updates

We have posted updates of the following topics:

Breast > Epithelial-myoepithelial tumors > Adenomyoepithelioma
by Melissa Krystel-Whittemore, M.D., Hannah Y. Wen, M.D., Ph.D.
Topic summary: Biphasic tumor composed of variable number of myoepithelial cells surrounding epithelial lined spaces. Benign to low grade malignant behavior and a propensity for recurrence. Usually presents as a solitary palpable mass or screen detected on breast imaging. Ultrasound: irregular / angulated or oval / circumscribed, hypoechoic mass. Tubular type of adenomyoepithelioma, intraductal extension along periphery of lesion, incomplete excision and cytologic atypia are associated with local recurrence. Complete wide excision with negative margins is standard treatment to prevent local recurrence.

Liver & intrahepatic bile ducts > Benign / nonneoplastic > Hemangioma
by Michael McCarthy, M.D., Lizhi Zhang, M.D.
Topic summary: Benign vascular tumors, predominantly asymptomatic with no reported malignant transformation. Classification is based on characteristic histologic features; there should be no significant cytologic atypia or mitotic activity. Most often found in right lobe of liver, particularly segment IV, subcapsular location. Precision pathogenesis unknown. Diagnosis is predominantly based on imaging studies. Core needle biopsy contraindicated due to risk of hemorrhage and low diagnostic yield. If small and asymptomatic, surveillance via serial imaging is sufficient.

Pleura & peritoneum > Peritoneum > Multicystic mesothelioma
by David B. Chapel, M.D., Aliya N. Husain, M.D.
Topic summary: Rare, bland mesothelial proliferation of uncertain pathogenesis. Numerous small cysts lined by a single layer of bland, flat to cuboidal cells. Approximately 50% recur but death from disease is exceptionally rare. Accounts for 3 – 5% of peritoneal mesothelial lesions, 80 – 90% occur in women. Essentially all cases involve the pelvis. Commonly presents with abdominal fullness, pain or urinary / bowel symptoms. Diagnosis involves laparoscopic exploration with tissue sampling. Early complete surgical resection is first line therapy.

Skin nontumor > Dermal perivascular and vasculopathic reaction patterns > Erythema elevatum diutinum
by Kiran Motaparthi, M.D.
Topic summary: Rare, chronic fibrosing vasculitis associated with a variety of systemic diseases. Red-brown plaques and nodules observed on extensor and acral surfaces. Most commonly affects adults between 30 – 60 years of age but earlier onset observed in association with human immunodeficiency virus (HIV) infection. In early disease, IL8 recruits neutrophils to sites of involvement. May resolve spontaneously over 5 – 10 years but can also persist for decades. Oral dapsone monotherapy is effective in 80% of cases, particularly in early disease.

Soft tissue > Fibroblastic / myofibroblastic > Ossifying fibromyxoid tumor
by Borislav A. Alexiev, M.D.
Topic summary: A distinctive mesenchymal neoplasm of uncertain differentiation, with cords, nests, clusters and sheets of uniform ovoid cells embedded in a variable myxoid, fibromyxoid or hyalinized stroma, often with an incomplete peripheral shell of bone. Occurs over a wide age range (14 – 83 years) with a median age of about 50 years. PHF1 gene rearrangement has been observed in 80% of cases, including benign, atypical and malignant subtypes with fusion to EP400 in 44% of cases. Has unpredictable potential for local recurrence and metastasis. Tumor resection and clinical follow up are considered to be the appropriate management of the tumor at present.

28 December 2020: Textbook Updates

We have posted updates of the following topics:

Liver & intrahepatic bile ducts > Drug / toxin induced hepatitis > Methotrexate
by Maryam Aghighi, M.D., Raul S. Gonzalez, M.D.
Topic summary: Methotrexate in liver can cause reactive changes, steatosis or fibrosis and rarely lymphoma. Mild elevation in liver enzymes, fibrosis and cirrhosis may be observed due to extended usage. Incidence rate of liver enzymes elevation in patients with low dose methotrexate therapy is 13 per 100 patient years. Clinically, patients may be asymptomatic or present with jaundice, hepatomegaly or constitutional symptoms including weight change and fever. Folic acid supplement of 1 mg per day lowers the risk of liver enzymes abnormality, mouth ulcers and gastrointestinal issues such as nausea and vomiting.

Lymphoma & related disorders > Mature B cell neoplasms > Small B cell lymphomas with a circulating component > CLL / SLL
by Béla Kajtár, M.D., Ph.D.
Topic summary: Indolent mature B cell lymphoma with clonal proliferation of B cells with characteristic phenotype. Most common adult leukemia in the Western world. Sites include lymph nodes, bone marrow, spleen and peripheral blood. Involves clonal restriction of specific B cell populations with reduced competition of remaining B cell clones due to aging. Treatment is tailored based on clinical progression (progressive bone marrow failure, progressive or bulky lymphadenopathy, short lymphocyte doubling time, etc.), biological fitness of patient, presence of TP53 mutation / 17p deletion and IGH mutation status.

Pancreas > General > Cytology
by Maria Luisa C. Policarpio-Nicolas, M.D.
Topic summary: Normal and nonneoplastic findings in pancreas cytology. Normal cellular elements include acinar, ductal and islet cells (rare). Sites include head / uncinate, body and tail of pancreas. Common diagnostic procedures utilized in the procurement of pancreatic cytology samples include endoscopic ultrasound (EUS) guided FNA, endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC).

Prostate gland & seminal vesicles > Atypical / intraductal lesions > High grade prostatic intraepithelial neoplasia (HGPIN)
by Margaret Sanders, M.D., Murali Varma, M.B.B.S.
Topic summary: Putative precursor of prostatic adenocarcinoma. A diagnostic feature is prominent nucleoli visible at 200x or lower magnification. Surrogate marker for missed cancer in negative prostate biopsies; less useful in contemporary practice as lower incidence of unsampled prostate cancer with extended biopsy protocols. Diagnosis is made on histologic examination of biopsied prostate tissue, typically from a needle core biopsy. Treatment includes follow up PSA and repeat biopsy if PSA remains elevated.

24 December 2020: Textbook Updates

We have posted updates of the following topics:

Bone marrow neoplastic > Bone marrow – neoplastic myeloid > Recurrent genetic abnormalities > AML with mutated RUNX1
by Oluwatobi “Tobi” Odetola, M.D., Kamran M. Mirza, M.D., Ph.D.
Topic summary: Provisional entity in the 2016 WHO classification describing a de novo acute leukemia diagnosed with ≥ 20% blasts in blood or bone marrow. Reportedly accounts for 4 – 16% of cases of AML. Runt related transcription factor 1 (RUNX1) is known to play a key role in hematopoiesis as a key regulator of genes involved in the differentiation of myeloid cells. AML with mutated RUNX1 is currently treated with standard induction chemotherapy, including regimens consisting of cytarabine and an anthracycline. However, overall response rate, progression free survival and overall survival are known to be poor in the AML subtype.

Breast > Breast cancer > Triple negative breast cancer
by Joshua J.X. Li, M.B.Ch.B., Gary M. Tse, M.B.B.S.
Topic summary: Breast cancers with absence of estrogen receptor (ER), progesterone receptor (PR) and HER2 immunohistochemistry (IHC) expression. Overlaps with basal-like breast cancers, which are defined by gene expression profiling. Clinical favorable prognostic factors include pathologic complete response to neoadjuvant chemotherapy. Similar gross features to nontriple negative breast cancer. Complete surgical excision remains mainstay of curative treatment. Neoadjuvant treatment generally reserved for locally advanced disease but recommended also for early (up to pT1cN0M0) disease.

Breast > Fibrocystic changes > Apocrine adenosis / atypical apocrine adenosis
by Julie M. Jorns, M.D.
Topic summary: Defined as the presence of apocrine cytology in a recognizable terminal duct lobular unit (TDLU) associated with sclerosing adenosis. Lobulocentric proliferation with distortion by stromal fibrosis / sclerosis and apocrine cytology. Most frequent in third to fourth decades but occurs over a wide age range. Considered a part of the spectrum of fibrocystic changes. Diagnosis is based on histologic examination of tissue with or without immunohistochemistry. Presence of apocrine adenosis alone in a core biopsy does not require surgical excision.

Breast > Metaplastic carcinoma > Low grade adenosquamous
by Paula S. Ginter, M.D.
Topic summary: Rare variant of metaplastic carcinoma comprised of an intimately admixed combination of bland, well developed glands and solid squamous cell nests within a fibrotic or cellular spindle stroma. Largely clinically indolent with a favorable prognosis but may be locally aggressive. Association with other proliferative and sclerosing breast lesions has led some to suggest they represent precursors. Frequently presents as a palpable mass, typically < 5 cm. Most frequently diagnosed via surgical resection. Treatment involves surgical excision with negative margins.

21 December 2020: Textbook Updates

We have posted updates of the following topics:

Transfusion medicine > Transfusion therapy > Platelet use
by Rachel Jug, M.B.B.Ch., B.A.O., Katerina Pavenski, M.D.
Topic summary: Platelets are derived from single donor apheresis or pooled whole blood (from 4 – 6 donors) collections from volunteer donors who meet the donor health questionnaire and other screening requirements. Platelets are activated upon exposure to extracellular matrix of injured endothelium to adhere and aggregate, which forms a hemostatic plug. Risks associated with platelet transfusions include febrile reaction, allergic reaction and bacterial sepsis. Platelets are stored at room temperature under constant agitation to prevent cold platelet storage lesion and aggregation, respectively.

Transfusion medicine > Red blood cell antigens > Rh group
by Brian D. Adkins, M.D., Garrett S. Booth, M.D., M.S.
Topic summary: Most antigenic blood group outside of ABO. Rh (Rhesus) antigens are widely expressed in the donor population. Antibodies can cause hemolysis and hemolytic disease of the fetus and newborn (HDFN). RhD sensitization occurs during the first pregnancy due to maternal exposure to fetal hemorrhage during gestation or delivery; this leads to an anti-D IgG antibody which can cross the placenta in subsequent pregnancies. RhIg dosage may be administered in pregnant patients and in patients after exposure to RhD positive products.

Transfusion medicine > Transfusion therapy > Whole blood therapy
by Bryon Jackson, M.D.
Topic summary: Cold, stored whole blood (WB) may be stored at 1 – 6°C for up to 35 days (should be distinguished from fresh, warm whole blood). Used primarily in the treatment of trauma patients with massive bleeding. Cold storage may improve the hemostatic function of platelets due to increased in vivo aggregation and superior correction of bleeding time of cold-stored relative to warm-stored platelets. Delivers all components in a single product, providing early inclusion of plasma in trauma patients to address the coagulopathy of trauma.

Vulva, vagina & female urethra > Nontumor > Fibroepithelial (stromal) polyp
by Albert Alhatem, M.D., Debra S. Heller, M.D.
Topic summary: Benign mesenchymal mass characterized by a polypoid proliferation of the stroma with overlying squamous epithelium. The key to diagnosis is the characteristic stellate and multinucleated stromal cells. Occurs in reproductive age women, often during pregnancy or in postmenopausal women taking hormone replacement therapy. Most common in vagina and usually asymptomatic but can occasionally cause bleeding, discharge and general discomfort. Surgical excision is curative. Recurrence is possible if incompletely excised.

17 December 2020: Textbook Updates

We have posted updates of the following topics:

Bone & joints > Other chondrogenic tumors > Chondromyxoid fibroma
by Qurratulain Chundriger, M.B.B.S., Nasir Ud Din, M.B.B.S.
Topic summary: Benign cartilaginous tumor, mostly in young adults in second and third decades of life and more commonly in males. Arises in proximal or distal parts of long bones, showing zonal architecture. Characteristic radiologic appearance; i.e. eccentric lytic lesion with sharp, sclerosed and scalloped intramedullary edges. Diagnosis requires integration of radiological and histopathological findings. En bloc resection of the tumor is the treatment of choice.

Laboratory Administration & Management of Pathology Practices > Quality / performance improvement > Principles of laboratory quality improvement
by Yaolin Zhou, M.D.
Topic summary: Quality improvement (QI) is the framework to systematically improve patient care. Multiple quality improvement models and tools are available but the one that you can remember and use is the best one. EPIDEM is a quality improvement approach that involves exploration, promotion, implementation, documentation, evaluation and modification.

Placenta > Abnormal Placentation > Placenta accreta, increta and percreta
by Fabiola Medeiros, M.D.
Topic summary: Abnormal placental adherence to the uterine wall. Patients with previous cesarean sections and placenta previa are at high risk for the development of abnormal placental implantation, which includes (1) placenta accreta, villi implant on the myometrial surface without intervening decidua, (2) placenta increta, villi extend into the myometrium and (3) placenta percreta, villi penetrate the entire myometrial thickness and through the uterine serosa. Massive peripartum hemorrhage needs immediate treatment with blood transfusions and management of disseminated intravascular coagulation and shock.

Transfusion medicine > Red blood cell antigens > ABO / H group
by Brian D. Adkins, M.D., Garrett S. Booth, M.D., M.S.
Topic summary: Most clinically important blood group; incompatible red blood cell transfusion causes intravascular, complement mediated hemolysis; antibodies are clinically significant. Patient’s blood type is based on their ABO phenotype. Bombay phenotype occurs when patients lack H antigen and naturally form anti-H antibodies. Acquired B antigen can occur due to enzymatic modification of the A antigen by enteric bacteria in patients with sepsis.

Transfusion medicine > Transfusion therapy > Massive transfusion
by Mrigender Virk, M.D.
Topic summary: Traumatic injury is the most common cause of hemorrhage requiring massive transfusion; other causes include gastrointestinal, obstetric and surgical bleeding. Severe blood loss leading to the lethal triad of trauma (hypothermia, coagulopathy, acidosis). Progressive symptoms depending on severity of hemorrhagic shock. Laboratory values may be normal in early acute hemorrhage and progressively deteriorate as interstitial fluid enters the intravascular space and crystalloids are infused. Transfuse RBCs, platelets and plasma in 1:1:1 ratio.

14 December 2020: Textbook Updates

We have posted updates of the following topics:

Pancreas > Exocrine carcinomas > Molecular aspects of pancreatic cancer
by Claudio Luchini, M.D., Ph.D.
Topic summary: Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, representing > 90% of all pancreatic malignancies. Somatic mutations affect, above all, four genes: KRAS, which is an oncogene and TP53, CDKN2A and SMAD4, which are tumor suppressor genes. Transcriptomic profile divides pancreatic cancer into different groups; among them, the squamous subtype has the worst prognosis. SMAD4 mutations are associated with more aggressive behavior and with a widespread metastasis pattern. Tumors with germline BRCA mutations can be treated with platinum based therapy and with PARP inhibitors.

Salivary glands > Inflammatory > Chronic sialadenitis / sialolithiasis
by Kim A. Ely, M.D.
Topic summary: Repeated episodes of pain and inflammation due to impedance of salivary flow with stasis as a result of obstruction from a sialolith. Mostly affects the submandibular gland (80%) unilaterally without a side predilection. Sialolithiasis is estimated to affect 1/10,000 – 1/30,000 individuals in the 30 – 60 year age range with a higher incidence in males. Intermittent, periprandial pain and swelling of a single salivary gland. If inconclusive clinically, sialography is the gold standard for the diagnosis. Treatment is conservative, with excision reserved for the minority of cases.

Stains & molecular markers > MDM2
by Jennifer Yoest, M.D., Navid Sadri, M.D., Ph.D.
Topic summary: Murine double minute 2 (MDM2), located on 12q15, is amplified on supernumerary ring or marker chromosomes in many tumors, leading to suppression of p53. Discovered in 1987 when screening for amplified genes in a transformed mouse cell line. Amplification detected by comparative genomic hybridization, qualitative PCR, FISH or DISH; MDM2 immunostaining correlates with gene amplification. Used to distinguish well differentiated liposarcoma (positive) from benign adipose tumors (negative). MDM2 amplification is a proposed radiation, chemotherapy, tyrosine kinase inhibitor and immune checkpoint inhibitor therapy resistance mechanism.

Thyroid gland > Papillary thyroid carcinoma > Main variants > Diffuse sclerosing
by Livia Florianova, M.D., M.Sc., Marc Pusztaszeri, M.D.
Topic summary: Uncommon papillary thyroid carcinoma (PTC) variant characterized by diffuse involvement of 1 or both thyroid lobes with dense sclerosis, abundant psammoma bodies, solid foci with associated squamous metaplasia, chronic lymphocytic thyroiditis background and extensive lymphatic invasion. Highly prevalent in female pediatric / young patients and in patients affected by irradiation. Associated with higher rates of extrathyroidal extension (40 – 77%), lymph node metastases (68 – 86%) and distant metastases (11.6%) at presentation compared with conventional PTC. Should trigger aggressive therapeutic management in an effort to achieve a possibly excellent long term clinical outcome.

10 December 2020: Textbook Updates

We have posted updates of the following topics:

Anus & perianal area > Premalignant > Buschke-Löwenstein tumor
by Phuong Nhat Nguyen, M.D., M.Sc., Lewis A. Hassell, M.D.
Topic summary: Also known as giant condyloma acuminatum, this tumor was first described as a penile neoplasm by Buschke and Löwenstein in 1925; previously considered synonymous with verrucous carcinoma. Condylomatous squamous lesion without high grade dysplasia, with only low risk HPV types present, forming an exophytic mass, usually greater than 3 cm. Pathophysiology is similar to other skin and mucosal HPV induced tumors; viral DNA is incorporated into cellular DNA following exposure, redirecting cellular processes into dysregulated cellular proliferation. Preferred initial therapy: complete excision with wide margins.

Breast > Fibrocystic changes > Adenosis
by Julie M. Jorns, M.D.
Topic summary: Any hyperplastic process displaying increase in glands, typically within terminal duct lobular units. Subtypes include adenomyoepithelial, apocrine, sclerosing, tubular and nodular adenosis. Occurs in wide age range, highest in third and fourth decades, paralleling fibrocystic changes. Diagnosis is based on histologic examination of tissue with or without immunohistochemistry. With some subtypes, the risk of subsequent breast cancer is 1.5 – 2 times higher, as seen with proliferative fibrocystic changes. Does not require treatment unless there is cytologic atypia (rare).

Chemistry, toxicology & urinalysis > Organ specific > Liver > Liver function test panel
by Syeda F. Absar, M.D., M.P.H., Patricia Tsang, M.D., M.B.A.
Topic summary: Used for diagnosing liver disease in patients with history or clinical symptoms of liver dysfunction; aberrant test results may indicate the need for additional testing in order to assess the etiology. Tests in the panel include liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) as well as proteins. ALT is more liver specific than AST, even though both are elevated in liver disease. Graded proficiency testing (PT) provides an external check on a laboratory’s performance of the assays.

Kidney tumor > Childhood tumors > Mesoblastic nephroma
by Ellen D’Hooghe, M.D., Gordan M. Vujanic, M.D., Ph.D.
Topic summary: Mesenchymal / myofibroblastic renal tumor of low grade malignancy that typically occurs in infancy. Represents 3 – 4% of all renal tumors of childhood with median age < 1 month in 63% of cases and 90% of cases diagnosed in the first 9 months of life. 3 histologic subtypes: classic (~25% of cases), cellular (~65%) and mixed (~10%). No recognized risk factors. Imaging techniques cannot distinguish it from other renal tumors. Most important prognostic factor is completeness of surgical resection.

Lymphoma & related disorders > Mature B cell neoplasms > Large B cell lymphomas-special subtypes > ALK+ LBCL
by Nicholas Joseph Dcunha, M.B.B.S., M.D., Marie Therese Manipadam, M.B.B.S., M.D.
Topic summary: WHO defines this entity as an aggressive neoplasm of ALK (anaplastic lymphoma kinase) positive monomorphic large immunoblast-like B cells, which usually have a plasma cell phenotype. It is a very rare lymphoma. Common sites include lymph nodes and mediastinum. Diagnosis is based on a combination of light microscopy and immunohistochemical markers. Most cases are treated with chemotherapy regimens of CHOP or E-POCH / CHOEP; a few patients are also given additional radiotherapy.