12 April 2021: Textbook Updates

We have posted updates of the following topics:

Bone & joints > Chondrosarcoma > Chondrosarcoma (primary, secondary, periosteal)
by Akif K. Guney, M.D., Shadi Qasem, M.D.
Topic summary: Locally aggressive or malignant group of tumors characterized by formation of cartilaginous matrix. Primary: arising without a benign precursor. Secondary: arising in preexisting enchondroma or preexisting cartilaginous cap of an osteochondroma. Periosteal: occurs on the surface of the bone in association with the periosteum. Histologic grade, extracompartmental spread and local recurrence are important prognostic factors. Accounts for ~20% of all malignant bone tumors. Most common sites are the pelvic bones, femur and humerus. Pain, local swelling and enlarging mass are the most common presenting symptoms. Diagnosis of chondrosarcoma can be made on imaging studies (Xray, CT scan, MRI) in combination with biopsy specimen. Wide surgical resection is the mainstay of treatment.

Bone marrow neoplastic > Bone marrow – neoplastic myeloid > Myeloid / lymphoid neoplasms with eosinophilia and gene rearrangement > PCM1-JAK2
by Monika Nageshwar, M.B.B.S., M.D., Zeba N. Singh, M.B.B.S., M.D.
Topic summary: PCM1-JAK2 fusion is a rare genomic abnormality resulting from t(8;9)(p22;p24.1), which fuses the Janus activated kinase 2 gene (JAK2) with the human autoantigen pericentriolar material gene 1 (PCM1), resulting in a constitutively activated tyrosine kinase. Morphology usually like an MPN, MDS / MPN or acute leukemia, both myeloid and lymphoid. Sites: peripheral blood and bone marrow. Diagnosis: review of the CBC and peripheral smear evaluation; if eosinophilia is present, all secondary causes of eosinophilia should be excluded clinically and by appropriate investigation. Neoplasms resulting from –PCM1-JAK2 mutation do not respond to imatinib; the JAK1/2 inhibitor ruxolitinib has shown good response, although eventually these patients require allogenic stem cell transplantation.

Lymphoma & related disorders > HHV8 associated lymphoproliferative disorders > HHV8 related germinotropic lymphoproliferative disorder
by Jayalakshmi Venkateswaran, M.D., Julie Teruya-Feldstein, M.D.
Topic summary: Monotypic HHV8 positive lymphoproliferative lesion occurring characteristically in HIV negative patients. Coinfection of HHV8 and EBV. No known epidemiological association. Uncertain contribution of EBV in pathogenesis. Localized, sometimes multifocal lymphadenopathy in otherwise healthy individuals. Very few descriptions of radiological features reported so far. Overall favorable response to chemotherapy and radiation. Treatment approach is variable; some cases have not been treated, while others have been treated with surgery alone or with chemotherapy and radiation.

Lymphoma & related disorders > Mature T/NK cell disorders > Intestinal > Indolent T lymphoproliferative disease of the GI tract
by Anamarija M. Perry, M.D.
Topic summary: Clonal T cell lymphoproliferative disorder (T-LPD) that involves the mucosa of gastrointestinal (GI) tract. Rare, approximately 50 reported cases; most commonly diagnosed in fifth and sixth decade, with a broad age range (23 – 79 years). Generally involves small intestine and colon but any GI site can be involved. Most common presenting symptoms are abdominal pain and diarrhea. Diagnosis: biopsy of affected GI site. No specific prognostic factors identified. Poor response to conventional chemotherapy and immunotherapy; so far, there is no successful treatment.

Uterus > Smooth muscle tumors > Leiomyoma-general
by Léonie Alran, B.S., Agnieszka Rychlik, M.D., Sabrina Croce, M.D., Ph.D.
Topic summary: Most common uterine tumor. Benign mesenchymal tumor derived from smooth muscle. All ages, especially in fifth decade; third decade for fumarate hydratase deficient leiomyoma. Sites: uterine corpus; less common in vulva, vagina, cervix, broad ligament, ovary. Mitotically active leiomyoma: associated ischemia or hormonal stimulation (endogenous or exogenous). Diagnosis can be established by resection of the whole uterus (hysterectomy), by resection of the leiomyoma if accessible by curetting (if submucosal) or by myomectomy (if subserosal). Asymptomatic: does not require therapy. Symptomatic leiomyoma: surgery (hysterectomy or myomectomy); hysteroscopic resection.

8 April 2021: Textbook Updates

We have posted updates of the following topics:

Breast > Fibroepithelial tumors > Tubular adenoma
by Joshua J.X. Li, M.B.Ch.B., Gary M. Tse, M.B.B.S.
Topic summary: Benign fibroepithelial tumor of the breast composed of compact bilayered tubules with sparse intervening stroma. Found in 2.8% of cases in a series of breast biopsies; most identified in young (20 – 40 years old) women and rarely in postmenopausal age group. May be associated with reproductive hormones due to high incidence in women of reproductive age. Histology recommended for definitive diagnosis; radiology and cytology usually allow identification of the benign nature of lesion but may not be sufficient in excluding differential diagnoses. Benign, indolent lesions; no increased risk of developing subsequent breast carcinoma. Curable by complete surgical excision.

Breast > Metaplastic carcinoma > Metaplastic
by Huina Zhang, M.D., Ph.D.
Topic summary: Heterogeneous group of invasive breast carcinomas characterized by differentiation of the neoplastic epithelium towards squamous cells or mesenchymal looking elements, including but not restricted to spindle, chondroid and osseous cells. Uncommon (0.2 – 1% of breast carcinomas); average age 55 years. Tends to have large tumor size, less nodal involvement and higher American Joint Committee on Cancer (AJCC) stage. Diagnosis by histopathological examination. Fibromatosis-like carcinomas and low grade adenosquamous carcinomas are associated with more indolent behavior. Treatment: mastectomy or local excision, with or without radiation and chemotherapy.

Placenta > Nonneoplastic placental conditions and abnormalities > Noninfectious > Maternal vascular malperfusion
by Jasmine Steele, M.D., Jonathan L. Hecht, M.D., Ph.D.
Topic summary: Conditions in which the functional capacity of the placenta is impaired due to altered maternal blood flow to the intervillous space. Reported incidence range is broad: 8% of low risk nulliparous women to 32.8% of term placentas in an unselected cohort. 2 patterns: global (small placenta with villous malformation: accelerated villous maturation or distal villous hypoplasia) and segmental (villous infarcts from occluded spiral arteries). Etiology: Maternal vascular disease; diabetes; chronic hypertension. Diagnosis: second and third trimester ultrasound for placental size of the placenta, uterine artery Dopplers or fetal growth delay. Close surveillance in subsequent pregnancy due to risk of recurrence (10 – 25%).

Salivary glands > Primary salivary gland neoplasms > Malignant > Acinic cell carcinoma
by Arash H. Lahouti, M.D., Rema A. Rao, M.D.
Topic summary: Low / intermediate grade malignant epithelial neoplasm of the salivary glands characterized by serous acinar cell differentiation (cytoplasmic zymogen granules) in at least some of the neoplastic cells. Approximately 6 – 8% of all salivary gland neoplasms and 10 – 17% of primary salivary gland malignancies. Most common site: parotid gland (80%). Radiology (ultrasound, CT or MRI) demonstrates presence and extent of mass lesion. 5 year survival: 97%; may recur years or decades after initial diagnosis. Radiotherapy may be indicated for tumors that cannot be completely excised or metastatic disease.

Transfusion medicine > Transfusion reactions & complications > Iron overload
by Maha Badawi, M.B.B.S.
Topic summary: Iron accumulates within various body organs after multiple transfusions. Occurs after transfusion of 10 – 20 units of red blood cells, affecting transfusion dependent patients. Each unit of red blood cells transfused contains 200 – 250 mg of iron. Asymptomatic at early stages; symptoms occur later after organ damage. Clinical features: heart failure, liver cirrhosis, diabetes, hypothyroidism, hypoparathyroidism, hypogonadism and skin hyperpigmentation. Patients who receive multiple transfusions must be screened for iron overload using serum ferritin measurement and organ assessment. Treatment is through iron chelators.

5 April 2021: Textbook Updates

We have posted updates of the following topics:

Bone marrow neoplastic > Bone marrow – neoplastic myeloid > Myeloid neoplasms with germline predisposition and other organ dysfunction with GATA2 mutation
by Zhenya Tang, M.D., Ph.D., Courtney D. DiNardo, M.D.
Topic summary: 1 of 5 subgroups of myeloid neoplasms with germline predisposition and other organ dysfunction in the entity of myeloid neoplasms with germline predisposition in the revised 2016 WHO classification. In children, adolescents and young adults, 7 – 15% of primary myelodysplastic syndrome cases and up to 37% of patients with monosomy 7 (-7) are associated with germline GATA2 mutation. No significant difference in overall survival between myeloid neoplasm cases with GATA2 mutation and those with same type of myeloid neoplasm but without germline GATA2 mutation. Treatment: same as each type of myeloid neoplasm (e.g. myelodysplastic syndrome, myeloproliferative neoplasm or acute myeloid leukemia).

CNS tumor > Sellar region tumors > Pituicytoma
by Federico Roncaroli, M.D.
Topic summary: Pituicytoma belongs to the group of tumors arising from the neurohypophysis and pituitary infundibulum, together with spindle cell oncocytoma and granular cell tumor. Histologic features include fascicles of spindle cells or epithelioid cells expressing TTF1, S100 protein and GFAP. Usually in adults: 40 – 60 years; no obvious male or female predominance. Ultrastructural similarities suggest an origin from light and dark pituicytes. Diagnosis made on histology. Behaves as benign tumor; recurrence can occur when incompletely excised (4% of cases). Complete surgical excision is curative.

Muscle & peripheral nerve nontumor > Inflammatory myopathies > Immune mediated necrotizing myopathy
by Chunyu “Hunter” Cai, M.D., Ph.D.
Topic summary: Pathological definition of immune mediated necrotizing myopathy (IMNM) requires prominent myofiber necrosis, the absence of significant inflammatory infiltrates, negative major histocompatibility complex (MHC) class I expression and variable complement deposition on capillaries. IMNM is further classified by serum autoantibodies into anti-SRP, anti-HMGCR and seronegative groups. Major target organ of anti-SRP and anti-HMGCR are muscles, leading to myofiber necrosis and weakness. Statin exposure is highly associated with anti-HMGCR myopathy. Prognosis of IMNM is in general worse than other types of myositis. Initial treatment includes intravenous or oral steroids.

Ovary > Mucinous tumors > Mucinous borderline tumor / atypical proliferative mucinous tumor
by Neshat Nilforoushan, M.D., Russell Vang, M.D.
Topic summary: Noninvasive mucinous neoplasm with complex architecture and gastrointestinal type differentiation. Ovarian tumors with mucinous epithelium of gastrointestinal type and epithelial proliferation (tufting, stratification and villus formation) involving > 10% of tumor. Mean age: 45 years. May arise from mucinous cystadenoma. Symptoms most often are related to pelvic mass. Diagnosis may be suggested by pelvic ultrasound. Excellent prognosis; stage I at diagnosis. Treatment: surgery with staging.

Placenta > Nonneoplastic placental conditions and abnormalities > Noninfectious > Decidual arteriopathy
by Jasmine Steele, M.D., Jonathan L. Hecht, M.D., Ph.D.
Topic summary: Pattern of injury to maternal vessels of the decidua that occurs in late pregnancy. Closely associated with preeclampsia and fetal growth restriction. Early lesions (hypertrophic type) show mural thickening due to continuous endothelial damage and repair. Hypertrophic decidual arteriopathy: small arteries with thickened walls, swollen endothelial cells that detach into the lumen and a sparse collection of perivascular lymphocytes. Severe decidual arteriopathy: characterized by fibrinoid necrosis of vessel wall (amorphous eosinophilic vessel wall); with or without foamy macrophages (atherosis).

1 April 2021: Textbook Updates

We have posted updates of the following topics:

Appendix > Appendicitis > Enterobius vermicularis
by Eiman Adel Hasby Saad, M.D.
Topic summary: Nematode infection caused by human pinworm Enterobius vermicularis. Enterobiasis is one of the most common worm diseases in humans, occurring predominantly in children via fecal – oral transmission and also by inhalation of dust containing eggs. F > M (5 – 14 year age group) but overall M:F = 2:1. Worms live and reproduce in the ileum, cecum, colon and appendix. While diagnosis may be made by histology, it can also be made clinically. Treatment: either mebendazole, pyrantel pamoate or albendazole; any of them given in 1 dose initially, then another dose of the same drug 2 weeks later.

Bone marrow neoplastic > Bone marrow – neoplastic myeloid > MDS / MPN > Atypical chronic myeloid leukemia
by Benjamin Graham, M.D., Lee Bentley Syler, M.D., Ling Zhang, M.D.
Topic summary: Atypical chronic myeloid leukemia (aCML) is a leukemic disorder with myelodysplastic / myeloproliferative features present at initial diagnosis. Clonal hematopoietic stem cell disorder that manifests with leukocytosis. Rare subtype of myelodysplastic / myeloproliferative neoplasm (MDS / MPN). Median age at presentation: ~70 years; M:F = ~1:1, with slight male predominance. Peripheral blood and bone marrow always involved. Poor prognosis; median survival = 15 months, 5 year overall survival = 25%. No standard treatment; allogeneic stem cell transplant (SCT) is only treatment that achieves long term remission.

Esophagus > Carcinoma > Undifferentiated carcinoma
by Ryan Kendziora, M.D., Rondell P. Graham, M.B.B.S.
Topic summary: Rare and aggressive esophageal carcinoma. Neoplastic cells appear high grade with frequent rhabdoid appearance. M > F; median age in seventh decade. Subset of cases has associated Barrett esophagus and Barrett associated dysplasia. Presentation similar to other esophageal cancers. Seen as exophytic mass on esophagogastroduodenoscopy. Poor prognosis overall: currently 20% 1 year survival rate. Treatment: neoadjuvant chemotherapy followed by esophagogastrectomy.

Kidney nontumor > Infection > Acute pyelonephritis
by Shelby Barnachea, B.S., Jian-Hua Qiao, M.D.
Topic summary: Acute suppurative (pus forming) infection of kidney collecting system as well as renal parenchyma. E. coli is the most common uropathogen isolated from urine or pus cultures in almost 70% of cases. More common in women and in patients with diabetes. Impaired tissue perfusion and impaired immune response. Best imaging study for diagnosis is CT of kidneys, ureters and bladder. Early, mild cases treated with antibiotics and percutaneous drainage (PCD) have a good outcome; in advanced cases, treatment with nephrectomy has the best outcome.

Liver & intrahepatic bile ducts > Other malignancies > Combined hepatocellular carcinoma-cholangiocarcinoma
by Nathalie Guedj, M.D., Ph.D., Aurélie Beaufrère, M.D.
Topic summary: Combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CC) is a rare primary liver malignancy with unequivocal presence of both hepatocytic and cholangiocytic differentiation. cHCC-CC is predominantly observed in male patients. Gold standard diagnosis is based on histologic analysis of resected specimens after extensive tumor sampling. Prognosis is worse than hepatocellular carcinoma and similar to that of intrahepatic cholangiocarcinoma. Management of cHCC-CC is not standardized; surgical resection with lymph node dissection is the only curative option.

29 March 2021: Textbook Updates

We have posted updates of the following topics:

Colon > Inflammatory bowel disease > Inflammatory bowel disease, indeterminate type
by John D. Paulsen, M.D., Alexandros D. Polydorides, M.D., Ph.D.
Topic summary: Inflammatory bowel disease (IBD), indeterminate type is a provisional term used to describe cases of IBD in which a definitive diagnosis of ulcerative colitis or Crohn’s disease cannot be established on the basis of histopathological and clinical (including radiologic and endoscopic) data. IBD, indeterminate type is a diagnosis of exclusion and requires conflicting histopathological findings in a resection specimen or in the setting of contradictory clinical, imaging and radiological data. Limited clinical utility of serological markers ASCA and pANCA. Given similar ileal pouch anal anastomosis failure rates as ulcerative colitis, ileal pouch anal anastomosis probably warranted.

Kidney tumor > Adult renal cell carcinoma – common > Clear cell
by Behtash G. Nezami, M.D., Gregory MacLennan, M.D.
Topic summary: Most common renal epithelial tumor, typically with clear cytoplasm and a compact nested or acinar growth pattern, intersected by delicate vasculature and with characteristic alterations to chromosome 3p involving VHL (von Hippel-Lindau) gene inactivation. Cortical mass with golden yellow variegated cut surface. Multiple tumors may represent familial syndromes but retrograde venous extension from the dominant sporadic tumor is also possible. Risk factors: smoking, obesity, hypertension, long term dialysis and family history of kidney cancer. 60 – 80% found incidentally on radiologic imaging. Surgical resection of stages 1 – 3 can be curative but up to 33% will recur.

Laboratory Administration & Management of Pathology Practices > Personnel Management > Building resilience in the workplace
by Lewis A. Hassell, M.D.
Topic summary: Resilient work environment and culture is one that is capable of responding to a variety of stresses without compromising effectiveness. Proactive, regular assessment of organizational strengths, weaknesses, opportunities and threats. Transparency of motives and goals, openness and humility throughout organization. Promote and offer stress reduction strategies, such as wellness, exercise or other healthy living tools. Following sound accounting and budgeting principles. Achieving and maintaining organizational trust via consistent performance, alignment of goals and methods with public and partners.

Skin nonmelanocytic tumor > Carcinoma (nonadnexal) > Basal cell carcinoma
by Antonina Kalmykova, M.D., Phillip H. McKee, M.D.
Topic summary: Arises from the interfollicular or follicular epithelium. Nests of basaloid cells with peripheral palisading associated with a fibromyxoid stroma. Most common cancer type in fair skinned people. UV radiation induced carcinogenesis. Nodular variant usually presents as a pearly pink or flesh colored papule or nodule with arborizing and branching vessels. Histological type associated with risk of local recurrence. Treatment: surgery, Mohs micrographic surgery; curettage and electrodesiccation for tumors with lower risk of local recurrence; radiation therapy.

Soft tissue > Fibroblastic / myofibroblastic > Solitary fibrous tumor
by Josephine K. Dermawan, M.D., Ph.D., Karen Fritchie, M.D.
Topic summary: Fibroblastic tumor characterized by haphazardly arranged spindled to ovoid cells, prominent staghorn vasculature and NAB2-STAT6 gene rearrangement. Occurs at any anatomical site, superficial and deep soft tissues, visceral organs and bone, with a wide range of histological patterns. Paracentric inversion involving chromosome 12q, resulting in NAB2-STAT6 gene fusion. Symptoms associated with anatomic location. Imaging features are nonspecific and diagnosis is dependent on histologic findings. 10 – 30% (local or distant) recurrence rate. Surgical resection remains gold standard of treatment.

25 March 2021: Textbook Updates

We have posted updates of the following topics:

Microbiology & parasitology > Fungi > Molds > Zygomycetes
by Alison Burkett, M.D., Sawanan Saitornuang, B.S., Sixto M. Leal, Jr., M.D., Ph.D.
Topic summary: Rapidly growing molds with worldwide geographic distribution. Pauciseptate, broad ribbon-like hyphae. Rapidly progressive angioinvasive disease. Most often affects immunocompromised patients and uncontrolled diabetics. Most common human infections: Rhizopus, Mucor, Rhizomucor. Diagnosis determined by direct examination in tissue. Surgical debridement and IV amphotericin B (lipid formulation) is standard therapy.

Skin nonmelanocytic tumor > Fibrous, fibrohistiocytic and myofibroblastic neoplasms > Atypical fibroxanthoma
by Pavandeep Gill, M.D., Phyu Aung, M.D., Ph.D.
Topic summary: Benign adnexal neoplasm of eccrine origin. Often multiple 1 – 4 mm, firm papules. Typically occurs after puberty; most common during reproductive years. Represents adenoma of acrosyringium, the intraepidermal eccrine sweat duct. Vulvar syringomas often present with pruritus and are often bilateral; oral contraceptive pills or menstruation may worsen symptoms. On face, in particular, can be clinically suspected; biopsy required for confirmation. Treatment necessary only for cosmetic reasons or quality of life; excision or cryotherapy / laser therapy is most common.

Skin nonmelanocytic tumor > Adnexal tumors > Sweat gland derived (apocrine & eccrine glands) > Syringoma
by Aadil Ahmed, M.D., Sara C. Shalin, M.D., Ph.D.
Topic summary: Rare low grade malignant cutaneous tumor of uncertain differentiation. Usually presents on the sun exposed skin of elderly patients with a slight male predominance. Associations with ultraviolet radiation exposure and ultraviolet radiation signature mutations in TP53, Li-Fraumeni syndrome, xeroderma pigmentosum, radiotherapy, immunosuppression, organ transplantation. Requires use of ancillary techniques (i.e. immunohistochemistry panels) to rule out other differential diagnoses. Treatment involves complete surgical removal with wide local excision or Mohs micrographic surgery.

Stomach > Polyps > Fundic gland polyp
by Naziheh Assarzadegan, M.D., Raul S. Gonzalez, M.D.
Topic summary: Benign cystic hyperplastic proliferation of oxyntic gland. Can be sporadic, associated with familial adenomatous polyposis (FAP) or arise as part of a familial condition confined to the stomach without polyposis coli. Most commonly encountered form of gastric polyps; peak incidence in fifth or sixth decade of life in sporadic cases and second and third decade in FAP patients. Current guidelines do not recommend polypectomy or surveillance endoscopy for sporadic cases.

Testis & epididymis > Sex cord-stromal tumors > Adult granulosa cell
by Kristine M. Cornejo, M.D.
Topic summary: Sex cord stromal tumor resembling granulosa cells of the Graafian follicles of the ovary. Rare, low grade, indolent tumor; 10% have malignant potential. Derived from granulosa cells in which FOXL2, a granulosa cell expressed gene, plays a role in regulating cell fate. Imaging studies may identify a testicular mass; definitive diagnosis is made by histopathologic examination only. Treatment: Radical orchiectomy; testis sparing surgery / wedge excision for smaller, benign tumors; retroperitoneal lymph node dissection and platinum based chemotherapy for metastatic disease.

22 March 2021: Textbook Updates

We have posted updates of the following topics:

Autopsy & forensics > General > Cause, manner, mechanism of death & death certificate
by Michelle Stram, M.D., Sc.M.
Topic summary: Cause of death (etiologically specific disease or injury) and the manner of death (how the death came about) are determined based on the circumstances of the death (determined by scene investigation, interviews, review of medical history), examination of the body (external exam, autopsy) and ancillary studies (toxicology, histopathology, vitreous chemistry, microbiology, etc.) as appropriate. Mechanism of death is the immediate physiologic derangement resulting in death (e.g. hemorrhage, sepsis, asphyxia), which is not etiologically specific. The purpose of the death certificate is to legally document occurrence of death and to provide mortality statistics for public health purposes.

Bone & joints > Other nonneoplastic > Ganglion
by Serenella Serinelli, M.D., Ph.D., Gustavo de la Roza, M.D.
Topic summary: Most common soft tissue mass found in the hand and wrist. 60 – 70% of the soft tissue masses in the hand and wrist; F:M = 3:1. Can occur at any age. Cystic fluid analysis: gelatinous material containing mainly hyaluronic acid and lesser amounts of glucosamine, globulins and albumen. Etiology is unclear. Clinical presentation is usually adequate for diagnosis. Ultrasound: well defined, unilocular or multilocular, noncompressible and anechoic or hypoechoic fluid collection. Benign condition; prognosis for most patients is excellent. Indications for treatment include pain, stiffness, weakness and cosmetic appearance.

Cervix > Premalignant / preinvasive lesions – H&E > HSIL / CIN II / CIN III
by Khaled J. Alkhateeb, M.B.B.S., Ziyan T. Salih, M.D.
Topic summary: Precancerous squamous proliferative lesion with full thickness nuclear atypia and varying degrees of cytoplasmic maturation. High risk (HR) HPV driven precancerous lesion (HPV 16 most common). 2 tier grading has better reproducibility: low grade squamous intraepithelial lesion (LSIL) / high grade squamous intraepithelial lesion (HSIL). Occurs in women of reproductive age, predominantly at transformation zone. Diagnosis: Cytology / Pap test. CIN II shows high spontaneous regression rate (42% and 50% at 12 and 24 months, respectively), particularly in young women (< 30 years). Treatment generally recommended for CIN II / CIN III or unspecified HSIL, except during pregnancy.

Ovary > Sex cord stromal tumors > Fibroma
by Gulisa Turashvili, M.D., Ph.D.
Topic summary: Benign stromal tumor composed of fibroblastic cells within a variably collagenous stroma. Important differential diagnoses for cellular fibroma include diffuse adult type granulosa cell tumor and fibrosarcoma. Most common ovarian stromal tumor; ~4% of all ovarian tumors. Neoplastic transformation of ovarian stromal cells due to hereditary or sporadic genetic abnormalities. Histologic examination for definitive diagnosis. Can lead to nonspecific increase in serum CA125. Prognosis is excellent in most cases. Treatment: surgical excision (salpingo-oophorectomy, oophorectomy or ovarian sparing procedure with or without hysterectomy depending on patient’s age).

Testis & epididymis > Sex cord-stromal tumors > Adult granulosa cell
by Kristine M. Cornejo, M.D.
Topic summary: Sex cord stromal tumor resembling granulosa cells of the Graafian follicles of the ovary. Rare, low grade, indolent sex cord stromal tumor; 10% have malignant potential. Mean age: 40 years (range: 14 – 87 years). Derived from granulosa cells in which FOXL2, a granulosa cell expressed gene, plays a role in regulating cell fate. Unilateral testicular mass or swelling. Imaging studies (e.g. ultrasound) may identify a testicular mass, definitive diagnosis is made by histopathologic examination only. Most are benign. Treatment: radical orchiectomy; testis sparing surgery / wedge excision for smaller, benign tumors.

18 March 2021: Textbook Updates

We have posted updates of the following topics:

Autopsy & forensics > Types of injuries > Therapy related deaths
by Mark A. Giffen, Jr., D.O.
Topic summary: Deaths which occur due to complications of medical treatment. A variety of medications and medically prepared solutions can result in complications which may cause or contribute to death. Vast majority of deaths during medical procedures occur as a direct result of the underlying natural disease process or injury which required the treatment. Despite safeguards, a variety of medical errors can occur during treatment. Comorbidities often potentiate or adversely impact medical complications. Some jurisdictions use a separate classification for most accidental or natural complications of medical treatment: therapeutic complication.

Lymphoma & related disorders > Mature T/NK cell disorders > T/NK cell disorders with a leukemic component > Aggressive NK cell leukemia
by Siba El Hussein, M.D., Joseph Khoury, M.D.
Topic summary: Aggressive NK cell leukemia (ANKL) is a rare disease with a dismal prognosis and many diagnostic challenges. ANKL overlaps morphologically and genetically with extranodal NK / T cell lymphoma; however, its clinical presentation is acute and outcome is poorer. Epidemiology: Asian population; median age 40 years; no gender predilection. Clinical features: Fever, B symptoms, hepatosplenomegaly, lymphadenopathy. Prognosis is very poor with a median survival of less than 2 months, despite intensive chemotherapy. Allogeneic hematopoietic stem cell transplantation improves outcome in ANKL patients for a limited time.

Skin nontumor > Dermal collagen and elastic tissue alterations, and cutaneous deposits > Atrophic papulosis
by Maryam Aghighi, M.D., Kiran Motaparthi, M.D.
Topic summary: Rare vasculopathy with benign skin limited form and frequently lethal systemic variant with intestinal involvement. Occurs in patients of all ages, mostly in young adults. More commonly affects proximal extremities and trunk. High interferon alpha expression and accumulation of late stage complements (C5b9) in diseased vessels. Early disease: up to 5 mm in diameter, skin colored papules on proximal extremities and trunk. Diagnosis methods include biopsy from skin, intestines or other involved organs. Benign atrophic papulosis: normal life expectancy, no systemic involvement. Average 2 year survival in untreated patients with systemic disease.

Soft tissue > Fibroblastic / myofibroblastic fibrosarcoma > Myxoinflammatory fibroblastic sarcoma
by Shima Rastegar, M.D., David Suster, M.D.
Topic summary: Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare, low grade sarcoma with prominent myxoid stroma, mixed inflammation, virocyte-like cells, pseudolipoblast-like cells and emperipolesis. Approximately 75% of tumors arise in the distal upper and lower extremities, including forearm, elbow, wrist, hand and fingers or ankle, feet and toes. Currently classified under tumors of unknown etiology. Clinicopathologic diagnosis: a combination of the appropriate clinical setting along with the characteristic histopathologic findings. Treatment involves wide local excision with or without radiation therapy. Completeness of initial surgical excision correlates with a lower incidence of recurrence.

Stains & molecular markers > DUX4
by Bradford Siegele, M.D., J.D.
Topic summary: Double homeobox 4 transcription factor, encoded by retrogene material within D4Z4 polymorphic macrosatellite repeat sequence. Nuclear marker with limited expression in normal tissues (fetal skeletal muscle, mature testis). Decreased epigenetic repression of the D4Z4 macrosatellite array and resulting expression of DUX4 is hypothesized to be primarily responsible for facioscapulohumeral dystrophy 1 (FSHD1) pathophysiology. Used to differentiate CIC-DUX4 fusion tumors from many other small round blue cell tumors in pediatric, adolescent and young adult population.

15 March 2021: Textbook Updates

We have posted updates of the following topics:

Bone & joints > Other tumors > Adamantinoma
by Borislav A. Alexiev, M.D., William B. Laskin, M.D.
Topic summary: Rare malignant primary bone tumor of uncertain histogenesis characterized by epithelial structures embedded in a mesenchymal (osteofibrous dysplasia-like) stroma. Wide age range: 4 – 75 (median age: 30.8 years); M:F = 5:4. In 85 – 90% of cases, the tumor is localized to median third of the diaphysis of the tibia. Previous studies provide strong arguments that the epithelial component of adamantinoma directly derives from the mesenchymal tissue and gradually increases in amount. The definitive diagnosis is mainly established by histopathological examination. Typically treated surgically with wide local resection; intralesional or marginal excision carries an increased risk of local recurrence.

Breast > Infectious > Filariasis
by Andrii Puzyrenko, M.D., Ph.D., Julie M. Jorns, M.D.
Topic summary: Lymphatic filariasis is caused by a chronic mosquito borne parasitic infection that involves the lymphatic vessels and lymph nodes of a human host. Inguinal (femoral) lymph nodes and lower extremities are most commonly involved. Mosquito deposits larvae into the bloodstream, which migrate to host lymph nodes and grow into adult worms. Antifilarial IgG1 and IgG4 antibody detected in peripheral blood by enzyme linked immunoassay (ELISA). Good prognosis if treated early. Diethylcarbamazine (DEC) is recommended as potential monotherapy; single combined dose of ivermectin, albendazole and DEC resulted in clearance of microfilaria in 96% of affected patients for up to 3 years. Surgical treatment may be an option.

Stains & molecular markers > Carbonic anhydrase IX
by Nick Baniak, M.D.
Topic summary: Member of zinc metalloenzyme family, which accelerates the rate of conversion between carbon dioxide (CO2) and bicarbonate (HCO3). Carbonic anhydrase IX (CAIX / CA9) is a transmembrane protein (membranous expression); primarily used in differentiating kidney tumors but not specific to renal primary tumors. CAIX is under control of the hypoxia inducible factor 1 (HIF1) and is predominantly located in chronically hypoxic tumor regions. Prognostic role under investigation in multiple organ systems; may be associated with worse outcome in clear cell renal cell carcinoma and papillary renal cell carcinoma.

Stomach > Lymphoma > MALT lymphoma
by Dorukhan Bahceci, M.D., Kwun Wah Wen, M.D., Ph.D.
Topic summary: Extranodal lymphoma composed of morphologically heterogeneous small B cells, including marginal zone (centrocyte-like) cells, cells resembling monocytoid cells, small lymphocytes and scattered immunoblasts and centroblast-like cells. Most gastric MALT lymphomas associated with gastritis caused by Helicobacter pylori infection. 7 – 8% of all B cell non-Hodgkin lymphomas; median age: seventh decade. Related to chronic inflammatory disorders driven by infectious agents or autoimmune stimuli. Diagnostic workup includes endoscopic findings, histology with immunohistochemistry and molecular analysis. H. pylori eradication is first line therapy; if this fails, second line therapy involves chemotherapy and radiation.

Testis & epididymis > Sex cord-stromal tumors > Leydig cell
by Zhengshan Chen, M.D., Ph.D., Manju Aron, M.D.
Topic summary: Most common sex cord stromal tumor of the testis, comprised of cells resembling nonneoplastic Leydig cells. Histology: diffuse / nodular growth of polygonal cells with abundant eosinophilic cytoplasm, uniform round nuclei and prominent central nucleoli; Reinke crystals may be present. 1 – 2% of testicular tumors in adults and 3 – 6% of testicular tumors in prepubertal males. Produces androgen, mainly testosterone, which can cause symptoms. Diagnosis: tumor histology and immunohistochemistry. Benign Leydig cell tumors: excellent prognosis, curative by surgery; malignant Leydig cell tumors: poor survival, most develop metastatic disease leading to death.

11 March 2021: Textbook Updates

We have posted updates of the following topics:

Bone marrow neoplastic > Bone marrow – neoplastic myeloid > Myelodysplastic syndromes (MDS) > Isolated del(5q)
by Natasha Iranzad, M.D., Endi Wang, M.D., Ph.D.
Topic summary: Myelodysplastic syndrome (MDS) characterized by anemia with or without other cytopenias or thrombocytosis in conjunction with chromosome 5q deletion with or without one additional cytogenetic abnormality apart from monosomy 7 or del(7q). Subtype of MDS in low risk group with relatively good prognosis. Loss of tumor suppressor genes in deleted region of 5q results in haploinsufficiency of several genes. Commonly presents with anemia, usually macrocytic, often severe. Median survival is approximately 5.5 – 12 years. Lenalidomide, a thalidomide analogue, has been shown to be beneficial.

CNS tumor > Meningeal tumors > Atypical meningioma
by Chunyu “Hunter” Cai, M.D., Ph.D., Jesse L. Kresak, M.D., Anthony T. Yachnis, M.D.
Topic summary: A meningioma of intermediate aggressiveness between benign and malignant forms, comprising 5 – 15% of meningiomas. 29 – 52% recur (versus 7 – 25% of classic meningiomas and 50 – 94% of anaplastic meningiomas). Arising from the meningothelial cells or the arachnoid layer. Clinical presentation of atypical and anaplastic meningioma is similar to their benign counterpart. Diagnose by imaging and pathology of biopsy / resection specimen. Gross total resection; postsurgical radiation is often offered for atypical meningiomas, especially after a subtotal resection.

Gallbladder & extrahepatic bile ducts > Gallbladder nonneoplastic > Adenomyomatous hyperplasia
by Alan A. George, D.O., Monica T. Garcia-Buitrago, M.D.
Topic summary: Benign reactive nonneoplastic lesion of the gallbladder. Most common benign gallbladder polypoid lesion after cholesterol polyps. Also called adenomyoma, adenomyomatosis. F:M = 3:1; wide age range, most patients diagnosed in their 50s. Sites: gallbladder (fundus if localized), rarely extrahepatic bile ducts. Associated with chronic inflammation / injury (cholecystitis, cholelithiasis). Usually diagnosed by microscopic evaluation of hematoxylin and eosin stained slides. Ultrasound is the most commonly used imaging modality; CT or MRI may also be used.

Skin nontumor > Dermal non-granulomatous granulocyte-rich reaction patterns > Behçet disease
by Amira Elbendary, M.B.B.Ch., M.Sc.
Topic summary: An autoinflammatory multisystemic disease. Recurrent oral and genital ulcers in 90% of cases. Distinct geographic distribution pattern along the ancient Silk Road. Mucocutaneous, ocular, cardiovascular, renal, gastrointestinal, pulmonary, urologic, central nervous system, joint, blood vessel and lung involvement. Oral ulcerations (95% of cases) on lips, gingival, buccal mucosa and tongue, leaves no scars. Diagnosis based on international criteria for Behçet disease – point score system. Worst prognosis reported in patients with retinal vasculitis, where blindness can occur. Treatment is tailored to each patient’s clinical manifestations.

Soft tissue > Vascular > Malignant > Angiosarcoma
by S. Shawn Liu, M.D., Ph.D., Vindhya Bellamkonda, M.D., Thuy L. Phung, M.D., Ph.D.
Topic summary: Highly malignant neoplasm showing morphological or immunophenotypic evidence of endothelial differentiation. Irregularly shaped anastomosing vascular channels or sheet-like growth. Accounts for about 2 – 3% of all soft tissue sarcomas in adults. Pathogenesis of angiosarcoma is characterized by a rapid and extensive infiltrating overgrowth of vascular endothelial cells. Etiology is unknown in most cases. Patients typically present with a blue or purple lesion on the scalp or face that has been present for several months and can be rapidly growing. Surgical resection is the main treatment modality, in addition to chemotherapy and radiotherapy.