26 September 2022: Textbook Updates

We have posted updates of the following topics:

Liver & intrahepatic bile ducts > Hepatocellular carcinoma > HCC – sarcomatoid variant
by Daffolyn Rachael Fels Elliott, M.D., Ph.D., Ryan M. Gill, M.D., Ph.D.
Topic summary: Hepatocellular carcinoma (HCC) variant, partially or entirely composed of malignant spindle cells. Area of conventional HCC usually present to support the diagnosis. Patients tend to be older and predominantly male. Associated with expression of genes related to epithelial mesenchymal transition (EMT) and inflammation. Sarcomatoid change is more frequent in patients undergoing repeated chemotherapy or transarterial chemoembolization. Larger tumor size, advanced stage and higher incidence of extrahepatic disease compared to classic HCC. Worse prognosis compared to classic HCC. Treatment: surgical resection, radiofrequency ablation, transarterial chemoembolization (TACE), transplantation.

Lung > Infectious > Bacterial > Tuberculosis
by Hui-Hua Li, M.D., Ph.D., Jefree J. Schulte, M.D.
Topic summary: Infectious disease caused by Mycobacterium tuberculosis; disease can be manifested as primary, secondary and miliary tuberculosis. Hallmark is necrotizing granulomatous inflammation, composed of central necrotic zone surrounded by epithelioid histiocytes and Langhans type giant cells. Most commonly affects the respiratory system but other systems can be involved in disseminated disease. Risk factors: immunosuppression, including HIV / AIDS, chronic immunosuppressive therapy or an inborn immunodeficiency; occupational: mining, construction work, pneumoconiosis (silicosis). Suboptimal treatment and multidrug resistant strains contribute to morbidity and mortality.

Skin nonmelanocytic tumor > Benign (nonmelanotic) epidermal tumors or tumor-like lesions > Dermatosis papulosa nigra
by Negin Farsi, M.D., Sara C. Shalin, M.D., Ph.D.
Topic summary: Benign epidermal growth presented as hyperpigmented or skin colored papules on face and neck, most commonly found on patients with darker phototypes (Fitzpatrick type IV, V or VI). Generally asymptomatic papules without crusting, scaling or ulceration. Clinical: filiform, verrucous or pedunculated pigmented papule; histology: acanthosis, papillomatosis, hyperkeratosis and hyperpigmentation. Onset often late in adolescence, increasing numbers with age, common in adulthood and age > 60 years. No risk for transforming to malignancy; never regresses spontaneously. Treatment not necessary; for cosmetic purposes.

Stains & CD markers > CD30
by Mario L. Marques-Piubelli, M.D., Roberto N. Miranda, M.D.
Topic summary: CD30 is a transmembrane, type I, glycoprotein receptor from the tumor necrosis factor receptor (TNFR) superfamily. CD30 gene is located at 1p36, close to TNFR2 and OX40. BerH2: most commonly used clone to fabricate the antibody and has good correlation with mRNA levels of CD30; composed of 2 linear epitopes with identical sequence. Typically expressed in cytoplasmic / membrane compartments. Targetable biomarker: high expression by neoplastic cells, low expression by normal cells, extracellular localization. Used in differential diagnosis and assessment of lymphomas in which the neoplastic cells universally express CD30.

Stains & CD markers > Uroplakin II
by Harsh Batra, M.B.B.S., D.C.P., D.N.B., Anil Parwani, M.D., Ph.D., M.B.A.
Topic summary: Uroplakin II, a 15kDa protein that is part of the uroplakin family (UP1a, UP1b, UPII and UPIII), which forms the urothelial plaque covering the apical surface of the urothelium. Uroplakins are terminal differentiation products that are exclusively expressed in urothelial cells. Highly specific and moderately sensitive for urothelial carcinomas. Helpful in ascertaining the primary origin as urothelium, especially in cases where GATA3 is inconclusive. Moderate to strong, predominantly membranous and cytoplasmic staining reaction in virtually all umbrella cells in the urethra. Loss of UPII seen more frequently in higher grade lesions.

22 September 2022: Textbook Updates

We have posted updates of the following topics:

Bone & joints > Arthritis > Gout and gouty arthritis
by Sahar Suleman, M.B.B.S., Madiha Bilal Qureshi, M.B.B.S., Nasir Ud Din, M.B.B.S.
Topic summary: Gout is a metabolic disorder that affects joints, bones, skin and soft tissues; associated with hyperuricemia, which causes saturation of monosodium urate and eventual formation of crystals within tissue. Crystal induced inflammation leads to acute, severe, self limiting joint pain. More common in men than women (4:1). Presents in 3 ways: acute gout, tophaceous gout and chronic arthropathy. Maori and Pacific ethnicity is recognized as a prognostic factor for more severe outcomes in gout. Long term treatment: urate lowering therapies include xanthine oxidase inhibitors (e.g., allopurinol or febuxostat), uricosuric drugs (e.g., probenecid) or uricase agents (e.g., pegloticase).

Colon > Noninfectious colitis > Mastocytic enterocolitis
by M.J. Fernández-Aceñero, M.D., Ph.D.
Topic summary: Rare condition, described in 2006, occurring in cases of chronic intractable diarrhea; not intended as a specific diagnosis. Chronic diarrhea is a frequent health problem, affecting 5 – 10% of the adult population. Normal endoscopy; increase in the number of mast cells (immunological cells derived from a CD34+ progenitor in the bone marrow) in the gastrointestinal biopsies with sheet and nest formation. Can also be associated with abdominal pain or bloating. Treatment: antihistamines (H1 and H2); mast cell stabilizers, including cromolyn; steroids; inhibitors of mast cell mediators, inhibitors of tryptase and chymase; leukotriene antagonists; kinase inhibitor.

Kidney tumor > Adult renal cell carcinoma – rare > Tubulocystic
by Daniel Anderson, M.D., M.B.A., Maria Tretiakova, M.D., Ph.D.
Topic summary: Renal epithelial neoplasm composed exclusively of tubules and cysts lined by a single layer of cells with prominent nucleoli (equivalent to ISUP / WHO grade 3) and abundant eosinophilic cytoplasm. Well circumscribed tumor with spongy bubble wrap appearance. Rare (< 1% of renal tumors); mean age: 58.4 years (range: 30 – 74 years). Often an incidental finding. Diagnosis is made on gross and H&E with attention paid to strict criteria of tubular and cystic growth. Relatively indolent with < 10% cases showing disease progression, local recurrence or metastasis to bone, liver and lymph nodes. Treatment: radical or partial nephrectomy depending on tumor size and location in the kidney.

Testis & paratestis > Collecting duct and rete testis tumors > Adenocarcinoma of collecting ducts and rete testis
by Burak Tekin, M.D., Rafael E. Jimenez, M.D.
Topic summary: Rare malignant neoplasm originating from the epithelium of rete testis and associated with an aggressive clinical behavior. Diagnosis of exclusion, with the differential diagnosis including mesothelioma, metastatic adenocarcinoma and germ cell tumors, among other entities. Extremely rare, with fewer than 100 cases reported in the literature. Predictors associated with a favorable outcome: Tumor size < 5 cm, tumors confined to the testis.Treatment: options for primary rete testis adenocarcinoma are not standardized; consists of radical orchiectomy with or without retroperitoneal lymph node dissection, in combination with adjuvant chemotherapy or radiotherapy.

Transfusion medicine > Transfusion reactions & complications > Red blood cell alloimmunization
by Sara Bakhtary, M.D.
Topic summary: Red blood cell (RBC) alloimmunization is the formation of antibodies to non-self RBC antigens (excluding naturally occurring anti-A and anti-B); only occurs after exposure through transfusion, pregnancy or transplantation. RBC alloimmunization can result in acute hemolytic or, more commonly, delayed hemolytic transfusion reactions, which can be life threatening. Higher rates of RBC alloimmunization occurs in patients with sickle cell disease (19 – 43%), thalassemia major (5 – 45%) and myelodysplastic syndromes (15%). There is no specific treatment for RBC alloimmunization; if a patient has an identified RBC alloantibody or multiple alloantibodies, an RBC unit negative for the implicated antigen(s) should be selected for transfusion.

19 September 2022: Textbook Updates

We have posted updates of the following topics:

Breast > Papillary carcinoma > Encapsulated papillary carcinoma
by Evan R.J. Goyette, M.D., Kristen E. Muller, D.O.
Topic summary: Expansile papillary tumor, occurring in postmenopausal women, with low or intermediate grade nuclei surrounded by a fibrous capsule that lacks myoepithelial cells along the papillae and at the periphery or shows focal peripheral myoepithelial staining. Staged as ductal carcinoma in situ (DCIS) (i.e., Tis) in the absence of invasive carcinoma, due to indolent behavior and excellent prognosis. Epidemiology: postmenopausal women, seventh decade. Presentation may include palpable mass or nipple discharge. Diagnosis: histologic examination of tissue removed by biopsy or surgical excision. May be treated adequately with surgical excision alone, similar to in situ carcinoma.

Microbiology, parasitology & COVID-19 > Parasites-cutaneous / subcutaneous / soft tissue > Leishmania
by Joshua A. Lieberman, M.D, Ph.D.
Topic summary: Vector borne intracellular protozoan parasite, class: Kinetoplastida, order: Trypanosomatida. 3 forms: cutaneous, mucocutaneous (may be disseminated) and visceral. Transmitted by sandfly bite (genera: Phlebotomus, Lutzomyia); dogs are likely an important reservoir in and around human settlements. Associated with increased risk of mucosal leishmaniasis. Patients infected with Leishmania spp. from subgenus Viannia (L. [Viannia] spp.) are at increased risk of mucosal disease and treatment is indicated; guidelines are not unanimous, however, for immunocompetent persons with uncomplicated, low risk skin lesions caused by species outside subgenus Viannia.

Skin nontumor > Lichenoid and interface reaction patterns > Subacute cutaneous lupus erythematosus
by Constanza Lobos, M.D., Maria E. Mazzei, M.D.
Topic summary: Lupus erythematosus is an autoimmune disease that involves a pathological spectrum ranging from a skin limited disease to a severe multisystemic illness. Subacute cutaneous lupus erythematosus (SCLE) presents clinically as a photosensitive, nonscarring, nonatrophy producing eruption. F > M (6:1); more frequent in young to middle aged women. Pathophysiology: genetic predisposition, drug biotransformation and epigenetic dysregulation in different immune cells, NETosis and participation of the innate immune system. 3 out of 10 patients can develop systemic disease. Treatment: sun protection, topical corticosteroids, antimalarial therapy, systemic corticosteroids and other immunosuppressants are indicated when there are other organs involved.

Stomach > Polyps > Adenomas
by Cindy Wang, M.D., Teri A. Longacre, M.D.
Topic summary: Intestinal type adenoma: polypoid lesion with dysplastic intestinalized epithelium; foveolar type adenoma: polypoid lesion with dysplastic foveolar epithelium. Classified into low grade or high grade dysplasia. Intestinal type adenoma is the most frequent adenoma (89.1%). Predominantly asymptomatic. Diagnosed by upper endoscopy with biopsy / polypectomy. Intestinal type gastric adenoma is more likely (but still with low probability) to progress to gastric cancer as compared to foveolar type gastric adenoma. Treatment: endoscopic mucosal resection or endoscopic mucosal dissection.

Testis & paratestis > Nonneoplastic lesions > Atrophy
by Patricija Zot, M.D., Rafael E. Jimenez, M.D.
Topic summary: Testicular atrophy is a nonneoplastic process characterized by the disappearance of tubular or germinal epithelium and replacement with variable degrees of fibrosis. Microscopic features include small tubules with few or no viable germ cells and a relative predominance of Leydig cells. Etiology: Vascular accident, testicular torsion, thrombosis. Diagnosis: measurement of gonadotropin and testosterone levels, human chorionic gonadotropin stimulation test, measurement of anti-Müllerian hormone, inhibin B levels, INSL3 levels and karyotype analysis. Potential risk for germ cell neoplasia in testicular regression syndrome with retained viable germ cells. Surgical removal of the testicular remnant may or may not be necessary; procedure for removal of outflow obstruction, if fertility is desired.

15 September 2022: Textbook Updates

We have posted updates of the following topics:

Fallopian tubes & broad ligament > General > WHO classification
by Gulisa Turashvili, M.D., Ph.D.
Topic summary: WHO classification of tumors of the female genital tract; currently on 5th edition, published in 2020. No major updates, mostly refined definitions. Most high grade serous carcinomas of the ovary arise at the fimbriated end of the fallopian tube from a precursor lesion known as serous tubal intraepithelial carcinoma (STIC). Undifferentiated carcinoma of the fallopian tube is no longer a separate category.

Kidney nontumor > Renal allograft > Recurrent and de novo diseases
by Arzu Sağlam, M.D.
Topic summary: Diseases that recur or develop de novo in the renal allograft. Most native kidney diseases can recur or develop de novo in the allograft, including cardiovascular diseases / hypertension, diabetes, metabolic diseases, infectious diseases, drug toxicities, perfusion problems and cancer, in addition to de novo / recurrent primary glomerular diseases. With improvement in treatment of rejection related complications, recurrent and de novo diseases have become a significant contributing factor to graft dysfunction. Recurrent glomerulonephritis is associated with increased risk of graft failure. Maintenance immunosuppression to prevent rejection generally alters disease course in immune mediated glomerulonephritis in comparison to native kidneys.

Lymphoma & related disorders > Mature T/NK cell disorders > Intestinal > Intestinal T cell lymphoma, NOS
by Busra Bacik Goksu, M.D., Carlos A. Murga-Zamalloa, M.D.
Topic summary: Primary intestinal T cell lymphomas (ITCL) are rare malignancies that account for < 10% of intestinal lymphomas. Intestinal T cell lymphoma, not otherwise specified is a rare and aggressive variant. Fewer than 10 cases have been reported. Computed tomography (CT) scans can be performed to show intestinal wall thickening; however, a biopsy is required for diagnosis.Survival ranges from weeks to < 2 years after diagnosis. Treatment similar to the systemic peripheral T cell lymphoma, NOS counterpart and includes induction with CHOP chemotherapy (cyclophosphamide, doxorubicin hydrochloride [hydroxydaunorubicin], vincristine sulfate [Oncovin] and prednisone).

Ovary > Metastases to ovary > Colorectal adenocarcinoma
by Adam Lechner, B.M., Carlos Parra-Herran, M.D.
Topic summary: Secondary ovarian involvement by colorectal cancer (CRC) is, by definition, evidence of advanced tumor stage (pM1). Mimic of primary ovarian endometrioid or mucinous adenocarcinoma. Rate of metastases to the ovary (OM) among all ovarian malignancies varies from 15 – 30%. Spread to the ovaries can be hematogenous, lymphatic, transperitoneal or by direct extension. Median survival of 25.5 months when ovary is sole site of metastasis. Given the high frequency of ovarian involvement by CRC and the high proportion of cases that are unsuspected before oophorectomy, preoperative investigation in a patient with an ovarian mass should include consideration for colonoscopy.

Placenta > Gestational trophoblastic disease > Neoplasms > Epithelioid trophoblastic tumor
by Rachelle Mendoza, M.D., Sonali Lanjewar, M.D., M.B.B.S., Raavi Gupta, M.D.
Topic summary: Epithelioid trophoblastic tumor (ETT) is a very rare gestational trophoblastic tumor derived from neoplastic chorionic type intermediate trophoblasts. Histologic features include nodular and expansile growth pattern of nests and cords of relatively uniform tumor cells with distinct cell borders, moderate eosinophilic to clear cytoplasm and associated extracellular eosinophilic, hyaline-like material. Usually occurs in women of 15 – 48 years of age (mean, 36.1 years). Vaginal bleeding or menometrorrhagia is the most common symptom but amenorrhea can also occur. Metastasis is seen in 25% of patients; survival rate of 87 – 90%. Surgical resection is the definitive treatment.

12 September 2022: Textbook Updates

We have posted updates of the following topics:

Appendix > Benign tumors > Hyperplastic polyp
by Giby V. George, M.B.B.S., Aaron R. Huber, D.O.
Topic summary: Appendiceal hyperplastic polyps (HPs) are serrated proliferations in the appendiceal mucosa (similar to colorectal hyperplastic polyps) that are devoid of architectural and cytologic dysplasia. Frequently harbor KRAS mutations and are thought to be unrelated to the serrated pathway of colorectal neoplasia. Occurs equally in both men and women; wide age range but mostly in older patients in the sixth to eighth decades of life. Usually incidental finding in appendices removed for other reasons. Benign, not clinically relevant. Appendectomy is curative.

Bone & joints > Other chondrogenic tumors > Synovial & tenosynovial chondromatosis
by Aisha Memon, M.B.B.S., Nasir Ud Din, M.B.B.S.
Topic summary: Synovial chondromatosis is a benign, locally aggressive neoplasm characterized by multiple hyaline cartilaginous nodules involving joint spaces, subsynovial tissue or tenosynovium. Involves large joints, 60 – 70% of cases affecting the knee, followed by hip, shoulder, elbow, ankle and wrist. Rare neoplasm, with an estimated incidence of ~1.8 cases per million person years. Disease recurs in 15 – 20% of cases with higher rates reported in tenosynovial cases; malignant transformation is uncommon and occurs in 5 – 10% of cases. Treatment: arthroscopic or open removal of loose bodies with or without a synovectomy.

Liver & intrahepatic bile ducts > Hepatocellular carcinoma > HCC – lymphocyte rich
by Daffolyn Rachael Fels Elliott, M.D., Ph.D., Ryan M. Gill, M.D., Ph.D.
Topic summary: Rare subtype of hepatocellular carcinoma (HCC) designated by the WHO; characterized by a dense lymphoid infiltrate with more lymphocytes than tumor cells. Very rare tumor with limited clinical and outcome data. Approximately half of cases have underlying cirrhosis or chronic infection with hepatitis B / C. Imaging modalities for diagnosis of HCC: multiphasic computed tomography (CT) or magnetic resonance imaging (MRI). May have better prognosis in comparison to classic HCC; majority of patients present with low stage disease, a single lesion, and without vascular invasion. Treatment: surgical resection; radiofrequency ablation; transarterial chemoembolization (TACE); transplantation (e.g., Milan criteria, modified by some institutions).

Oral cavity & oropharynx > Oral cavity squamous cell carcinoma > SCC-general
by Sarah H. Glass, D.D.S.
Topic summary: Malignant neoplasm that arises from the mucosal epithelium of the oral cavity and shows variable squamous differentiation. Most common cancer of the oral cavity, with a variable clinical appearance and a predilection for the ventrolateral tongue; associated with tobacco, alcohol and betel quid. Globally, highest rates are seen in Melanesia and South Central Asia; it is the leading cause of cancer related death in India for men. Multifactorial with accumulation of genetic alterations; loss of function of TP53 mutations and CDKN2A inactivation are frequently seen. 5 year survival rate of 68.0%. Early staged lesions are often treated with surgery.

Ovary > Other nonneoplastic > Pregnancy luteoma
by Swati Bhardwaj, M.B.B.S., M.D., Tamara Kalir, M.D., Ph.D.
Topic summary: Self limited, hyperplastic (nonneoplastic) proliferation of large, luteinized ovarian cells during pregnancy, resulting in a tumor-like mass of the ovary that regresses spontaneously during puerperium. Microscopic features include diffuse sheets of round cells with abundant eosinophilic cytoplasm and round nuclei. 80% of patients are multiparous; luteomas are rare in primiparous women. Occurs due to nodular hyperplasia of theca interna cells. Usually asymptomatic, with the mass being incidentally detected at cesarean section or tubal ligation at the end of pregnancy. Treatment is usually not necessary as these are spontaneously resolving lesions.

8 September 2022: Textbook Updates

We have posted updates of the following topics:

Larynx, hypopharynx & trachea > Benign tumors / nonneoplastic > Papilloma
by Kavita Umrau, M.B.B.S., Bin Xu, M.D., Ph.D.
Topic summary: Benign, exophytic squamous epithelial proliferation that is composed of branching papillary fronds with central fibrovascular cores lined by hyperplastic nonkeratinizing squamous epithelium, usually associated with low risk human papilloma virus (HPV) infection; in particular, genotypes 6 and 11. Incidence: 43 per million in children, 18 – 23 per million in adults. Clinical course is unpredictable; adverse risk factors associated with aggressive behavior of the lesion (e.g., extralaryngeal spread and recurrence) include: HPV11 infection, younger age of onset, tracheostomy performed to avoid airway obstruction and previous invasive procedures. Surgical approach (including laser ablation) is the current standard of care.

Liver & intrahepatic bile ducts > Benign / nonneoplastic > Focal fatty change
by Nazire Ece Albayrak, M.D., Stephen C. Ward, M.D., Ph.D.
Topic summary: Steatosis is normally a diffuse process; however, a more localized form called focal fatty change (FFC) was first described in 1980. Benign, asymptomatic and incidental finding in 10 – 20% of livers. May be caused by relative ischemia due to decreased portal venous blood flow or decreased delivery of substances via the portal vein. Diagnosis: contrast enhanced ultrasound (CEUS); definitive diagnosis with biopsy can be established in clinically challenging cases where it is difficult to distinguish from metastatic disease. Causes no mass effect or symptoms; liver function tests are usually within normal limits.

Microbiology, parasitology & COVID-19 > Fungi > Molds > Hyaline molds
by Natalie Larsen, M.D., Valeria Perez, Sixto M. Leal, Jr., M.D., Ph.D.
Topic summary: Hyaline molds are heterogeneous molds characterized by a lack of pigmentation of hyphae. Hundreds of species are known to cause disease in humans. Major risk factors include neutropenia, phagocyte dysfunction, biologic agents (BTK inhibitors). Organisms are present in the soil and environment with worldwide distribution. Proven invasive fungal infection (IFI): histopathologic, cytopathologic or direct microscopic examination of a specimen obtained by needle aspiration or biopsy, in which hyphae or melanized yeast-like forms are seen accompanied by evidence of associated tissue damage. Molds are intrinsically resistant to echinocandins (micafungin).

Microbiology, parasitology & COVID-19 > Mycobacteria > Mycobacteria non-TB
by Ateeqa Mujeeb Ullah, M.D., Lili Lee, M.D.
Topic summary: Mycobacteria other than Mycobacterium tuberculosis (MTB) and Mycobacterium leprae. Low virulence ubiquitous organisms, found in water, soil, dust and vegetation, affecting mostly patients with pre-existing lung disease or immunosuppression. Transmitted through inhalation of aerosol droplets, leading to phagocytosis by alveolar macrophages in the lungs, causing local destruction and eventual granuloma formation with varying degrees of necrosis. Amikacin is an effective drug against most nontuberculous mycobacterial species.

Soft tissue > Skeletal muscle > Rhabdomyosarcoma > Pleomorphic rhabdomyosarcoma
by Erica Kao, M.D., Cecilia Belzarena, M.D, M.P.H.
Topic summary: High grade pleomorphic sarcoma composed of bizarre eosinophilic, round and spindle cells with skeletal muscle differentiation. Confirmed with immunohistochemistry for myogenin or myoD1. Male predominance (1.8:1). Rapidly growing, painful deep mass, most commonly of lower extremity. High propensity for metastatic spread; lungs are the most common site for metastases (77%). Clinical behavior and responsiveness to chemotherapy are similar to adult high grade soft tissue sarcomas; poor prognosis with median survival of 7 months.

1 September 2022: Textbook Updates

We have posted updates of the following topics:

Bladder, ureter & renal pelvis > Urothelial neoplasms – noninvasive > Papillary urothelial neoplasm of low malignant potential
by Daniel Athanazio, M.D., Ph.D.
Topic summary: Neoplastic proliferation of the urothelium in a papillary configuration, with no invasion through the basement membrane. Epithelial lining of fibrovascular cores is thicker than normal urothelium. Strong male predominance (M:F = 5:1). This diagnostic category is justified because the recurrence and progression rates of papillary urothelial neoplasm of low malignant potential (PUNLMP) are expected to be higher than urothelial papilloma and lower than low grade noninvasive urothelial carcinoma. Treatment: transurethral resection with no need of further topical treatments.

Cytopathology > Cytopathology techniques > Automation
by Reid Wilkins, M.D., Abdallah Flaifel, M.D., Tamar C. Brandler, M.D., M.S.
Topic summary: Automation in cytopathology refers to the process of slide preparation, image acquisition and image analysis with identification of abnormalities by automated machinery in conjunction with cytologist review. Has mainly been implemented in gynecologic cytopathology with the development of automation systems that utilize liquid based cytologic processing. Advantages: increased productivity, cytotechnologist satisfaction. Effectiveness: MAVARIC trial conducted in England found significantly lower sensitivity of detection of cervical intraepithelial neoplasia grade II (CIN 2) and above (0.92) compared to manual screening; comparable rates of detecting CIN 2 and above.

Laboratory Administration & Management of Pathology Practices > Qualifying board topics > Quality assurance > Validation of reference intervals and reportable range
by Duy K. Doan, M.D., Lewis A. Hassell, M.D.
Topic summary: Reference intervals (RI) are defined as the central 95% of laboratory test results obtained from a healthy reference population. Nearly 80% of physicians’ medical decisions are based on information provided by laboratory reports. Direct approach to establishing reference intervals: subjects representing the reference population are selected and sampled and the specimens are analyzed to determine the reference intervals. Indirect approach: results from specimens collected for routine purposes are used to determine the reference intervals. Validation of reference interval is a study to establish that an assay works as intended.

Prostate gland & seminal vesicles > Atypical / intraductal lesions > HGPIN with adjacent atypical glands
by Aliaksandr Aksionau, M.D., Y. Albert Yeh, M.D., Ph.D.
Topic summary: High grade prostatic intraepithelial neoplasia (HGPIN) with small atypical glands present in adjacent stroma. Adjacent atypical glands stained positive (focal or patchy) on p63 or CK903 immunohistochemical stains. Incidence of HGPIN with adjacent atypical glands (2.5%) is lower than that of HGPIN alone (4.3%). More commonly arises in the peripheral zone of the prostate. Higher cancer detection rates: HGPIN alone (23%), ASAP (37%), HGPIN and ASAP (33%). No definitive treatment for ASAP and HGPIN.

Skin nonmelanocytic tumor > Cysts > Proliferating pilar tumor
by Colleen J. Beatty, M.D., Viktoryia Kazlouskaya, M.D., Ph.D.
Topic summary: Proliferating pilar tumor (PPT) is an uncommon neoplasm within the dermis or subcutis that arises from the isthmus region of the outer root sheath of the hair follicle. Histologically resembles a trichilemmal cyst but with central lobules of squamous proliferation and variable atypia and mitotic figures. Elderly women are most commonly affected (80% of cases arise in females). Nonscalp location, recent rapid growth, size > 5 cm and histologic features of extensive necrosis, high mitotic activity, poor circumscription with areas of invasion and cytologic atypia are all concerning for more aggressive or malignant behavior. Complete surgical excision, either via wide local excision or Mohs micrographic surgery.

25 August 2022: Textbook Updates

We have posted updates of the following topics:

Bladder, ureter & renal pelvis > Urothelial carcinoma – invasive > Micropapillary
by Timothy Isaac Miller, M.D., M.A., Maria Tretiakova, M.D., Ph.D.
Topic summary: Aggressive histologic subtype of urothelial carcinoma (UC) comprised of small papillary clusters of neoplastic cells within lacunae and without fibrovascular cores. If micropapillary urothelial carcinoma (MPUC) is seen on biopsy, it is highly associated with muscularis propria invasive disease. Some studies independently suggest a poorer prognosis than CUC; however, other studies show that this is likely because it is diagnosed at advanced stage, when controlling for pathologic stage, patients have similar outcomes. Early radial cystectomy (RC) may improve survival.

Cervix > Inflammatory / infectious > Trichomonas vaginalis
by Soumya Jaladi, M.B.B.S., Ziyan T. Salih, M.D.
Topic summary: Trichomonas vaginalis is a primitive eukaryotic organism, a parasitic protozoan that causes trichomoniasis, which is a sexually transmitted disease. Trichomoniasis is the most prevalent nonviral sexually transmitted infection in the United States, affecting an estimated 3.7 million persons. Mainly affects women from ages 16 – 35 years but can occur in postmenopausal women. People with trichomoniasis can pass the infection to others, even if they do not have symptoms. Patients and their sexual partners are treated with metronidazole or tinidazole.

Lung > Preinvasive > Atypical adenomatous hyperplasia
by Sherman Lin, Matthew J. Cecchini, M.D., Ph.D.
Topic summary: Atypical adenomatous hyperplasia (AAH) is a small, localized proliferation of atypical pneumocytes (usually ≤ 5 mm) that line intact alveolar spaces. Discrete from alveolar parenchyma with proliferation of atypical pneumocytes. Commonly seen in lung resections as an incidental finding; in some series, AAH has been reported in ≤ 30.2% of female patients undergoing a resection for adenocarcinoma. CT surveillance; frequency and duration dependent on size of nodule. Patients are cured upon resection.

Oral cavity & oropharynx > Soft tissue tumors & proliferations > Ectomesenchymal chondromyxoid tumor
by Molly Housley Smith, D.M.D.
Topic summary: Rare, benign soft tissue tumor with striking predilection for the anterior dorsal tongue. Fewer than 120 well documented cases have been reported. Histopathologically demonstrates a well defined, often multilobulated tumor with ovoid, round, fusiform or polygonal cells within a sometimes myxoid, chondromyxoid or mucoid background. Average age ~40 years. 5 cases (< 10% of reported cases with follow up information) are reported to have recurred. Treatment: conservative surgical excision is recommended.

Soft tissue > Adipose tissue tumors > Other benign lesions > Hibernoma
by Saba Anjum, M.B.B.S., Zoonish Ashfaq, M.B.B.S., Nasir Ud Din, M.B.B.S.
Topic summary: Rare, benign, adipocytic tumor composed of variable proportions of brown fat cells admixed with white adipose tissue. Benign tumor comprising multivacuolated eosinophilic granular fat cells with small, central normochromic nuclei. Usually present from 2 – 75 years. Prognosis is good with no significant potential for recurrence. Treatment: wide local excision with negative margins; for patients not fit for surgery, routine surveillance may be considered.

18 August 2022: Textbook Updates

We have posted updates of the following topics:

Fallopian tubes & broad ligament > Broad ligament > Wolffian tumor / Female adnexal tumor of probable Wolffian origin
by Elena Lucas, M.D., Wenxin Zheng, M.D.
Topic summary: Adnexal tumor arising from remnants of Wolffian (mesonephric) duct. Heterogeneous histologic appearance. Rare, approximately 130 cases reported; median age 50 years, range 15 – 87 years. Prognostic factors: low malignant potential; most tumors behave in a benign fashion. Recurrence or metastases occur in 11 – 20% of cases; median of 48 months to recurrence (range 13 – 96 months). Treatment: hysterectomy and bilateral salpingo-oophorectomy; tumor debulking.

Microbiology, parasitology & COVID-19 > Filamentous bacteria > Actinomyces
by Natalie Larsen, M.D., Sixto M. Leal, Jr., M.D., Ph.D.
Topic summary: Gram positive genus containing over 40 species; Taxonomy: genera Actinobacteria, family Actinomycetaceae. Anaerobic; modified acid fast stain negative. More common in developing nations. Infection initiated upon access to tissues via trauma, surgical procedures, foreign bodies. Indolent, slowly progressing pyogranulomatous disease. Treatment: susceptible to penicillin and most antibiotics used to treat gram positive bacteria; intrinsic resistance to metronidazole.

Penis & scrotum > Dysplasia / carcinoma in situ > Penile intraepithelial neoplasia (PeIN)
by Diego F. Sanchez, M.D., Antonio L. Cubilla, M.D.
Topic summary: Intraepithelial neoplastic proliferation with variable degree of dysplasia, keratinization and nuclear atypia. Classified as HPV related / dependent or HPV unrelated / independent. Mean age is ~58 years old. PeIN is most commonly found in the glans and foreskin. Frequent recurrence (48%); low rate of progression to invasive carcinoma (2%). Treatment: local excision (Mohs surgery, glans resurfacing, glansectomy) is the most frequent approach.

Salivary glands > Nonneoplastic tumors/tumor-like conditions > Lymphoepithelial cyst
by Zahra Maleki, M.D.
Topic summary: Unilocular cysts that involve the parotid gland. Simple cyst lined by low stratified squamous epithelium surrounded by polymorphous lymphocytes with prominent germinal centers. Almost all arise in parotid gland. Sporadic lymphoepithelial cyst may result from cystic dilation of ducts within intraparotid or periparotid lymph node or branchial cleft remnants. Excellent prognosis. Treatment: conservative therapy, with institution of highly active antiretroviral therapy medication in HIV related cases.

Uterus > Carcinoma > POLE ultramutated endometrial carcinoma
by Lucy Ma, M.D.
Topic summary: Endometrial carcinoma harboring pathogenic mutations in the exonuclease domain of the POLE gene. Carries excellent prognosis compared to the other molecular subgroups, as defined by The Cancer Genome Atlas (TCGA) program. Patients are typically younger (median age ~55 – 60) than patients with non-POLEmut endometrial carcinomas. Treatment: surgery with or without adjuvant therapy (vaginal brachytherapy, pelvic radiotherapy and chemotherapy, depending on stage).

11 August 2022: Textbook Updates

We have posted updates of the following topics:

Liver & intrahepatic bile ducts > Acute and chronic hepatitis > Acute hepatitis-general
by Josef G. Venable, M.D., Annika L. Windon, M.D.
Topic summary: Acute hepatitis is largely a clinical term used to describe a sudden elevation in liver enzymes that lasts < 6 months in duration. Hepatotropic viruses account for the majority of cases, most commonly hepatitis A and B viruses. Symptomatic cases may present as fatigue, abdominal pain, nausea and vomiting, muscle aches or jaundice. Cases of acute hepatitis can resolve spontaneously with supportive therapy, progress to acute liver failure or develop into chronic liver disease. Treatment for acute viral hepatitis: supportive therapy; antiviral therapy for cases of acute hepatitis B.

Mediastinum > Thymoma > Thymoma
by Anja C. Roden, M.D.
Topic summary: Malignant epithelial tumor of the thymic gland. Lobulated architecture comprised of cellular lobules intersected by fibrous bands. Any age, peak 40 – 60 years old. Diagnosis suggested on chest Xray, confirmed by CT; possibly MRI. Prognostic factors: stage (TNM stage; previously Masaoka-Koga stage), in some studies prognosis independent of resection status and WHO subtype. Treatment: thymectomy with or without resection of adjacent structures depending on extent of tumor, whenever possible.

Skin melanocytic tumor > Nevi > Special site nevus
by Dean Holliday, M.D., Carlos N. Prieto-Granada, M.D.
Topic summary: Melanocytic nevi located on specific anatomical sites, such as the scalp, ear, breast, umbilicus, genital skin, acral skin, axilla and other flexural sites that may demonstrate atypical histologic features such as pagetoid spread, lentiginous growth and epidermal effacement. Acquired melanocytic nevi are thought to result from activation of oncogenes such as BRAF (usually BRAF V600E) or NRAS, resulting in clonal proliferation of melanocytes. Definitive diagnosis is made through histologic examination of excised specimen. Treatment: complete excision.

Soft tissue > Vascular > Benign > Intramuscular angioma
by Qurratulain Chundriger, M.B.B.S., Madiha Bilal Qureshi, M.B.B.S., Nasir Ud Din, M.B.B.S.
Topic summary: Benign vascular neoplasm arising within skeletal muscle, accompanied by variable amount of adipose tissue. Variable admixture of arteries, veins, lymphatics of cavernous / capillary or mixed type of vessels. Up to 90% of cases in adolescents and young adults. Incomplete excision is the most important factor in local recurrence (30 – 50%). Benign with no risk of malignant transformation. Complete surgical excision with clear margins is the recommended treatment.