硬脑膜 MALT 淋巴瘤：PathologyOutlines 专题全文（附 10 月 12 日教科书更新）MALT lymphoma of the dura (with Textbook Updates, 12 October 2026)

Scope: full text of the PathologyOutlines blog post “12 October 2026: Textbook Updates” (5 topic summaries and the featured image), plus the full topic page “MALT lymphoma of the dura” (all sections, 12 on-site images with captions, sample pathology report, differential diagnosis, practice questions and answers). The other 4 topics are included as blog summaries only.

Textbook Updates · 12 October 2026

We have posted updates of the following topics:

CNS & pituitary tumors > Lymphoma & histiocytic tumors > MALT lymphoma of the dura

by Giovanni Martino, M.D., Flavia Adotti, M.D., Antonio d’Amati, M.D., Martina Mandarano, M.D., Ph.D., Marco Gessi, M.D.

Topic summary: Extranodal, dural based, low grade B cell lymphoma of mucosa associated lymphoid tissue (MALT); can have plasmacytic differentiation. Mutations in TNFAIP3, NOTCH2 and TBL1XR1 genes and other chromosomal aberrations have been reported. Unlike other extranodal marginal zone lymphomas, no known pathogenetic mechanism has been described to date. Compression symptoms; most commonly headache, seizures and focal neurological defects. Indolent clinical course; most patients benefit from local treatment strategies.

Lung > Interstitial lung diseases associated with smoking > Alveolar macrophage pneumonia (desquamative interstitial pneumonitis)

by Akira Yoshikawa, M.D., Andrey Bychkov, M.D., Ph.D., Sakda Sathirareuangchai, M.D.

Topic summary: Rare form of idiopathic interstitial pneumonia characterized by accumulation of intra-alveolar macrophages with intracytoplasmic, finely granular brown pigment. Most cases are associated with cigarette smoking; may also occur in association with connective tissue disease, medications, inhalational exposures, aspiration or hereditary disorders. Diagnosis is based on clinical features, radiology and histopathology. Most common symptom is dyspnea, followed by nonproductive cough. Generally favorable prognosis with good response to treatment.

Skin nontumor > Other diseases of skin appendages > Acne vulgaris

by Andrew Kulbiski, M.D., Jayden Ray, D.O., Sepideh Nikki Asadbeigi, M.D.

Topic summary: Acne vulgaris is a common inflammatory skin condition that primarily affects the face and trunk. Clinical lesions range from noninflamed comedones to inflamed papules, pustules, nodules and cysts. Multifactorial pathogenesis involving increased sebum production, follicular hyperkeratinization, Cutibacterium acnes overgrowth and a resulting inflammatory immune response. In the Western world, acne vulgaris is highly prevalent among adolescents. Topical benzoyl peroxide, topical retinoids and topical antibiotics are first line treatments.

Skin nontumor > Infectious disorders > Chromoblastomycosis

by Peyker Temiz, M.D.

Topic summary: Chromoblastomycosis is an infrequent fungal infection that occurs sporadically in tropical and subtropical areas, caused by various darkly pigmented (dematiaceous) fungi. Granulomatous tissue reaction with neutrophilic abscess is seen. Primarily affects rural workers since it is caused by a variety of fungi found in soil, wood and decaying plant material. Most common in middle aged men. Infection usually appears on exposed skin, especially the lower legs and arms. Infection develops slowly, lasts for many years and is resistant to treatment.

Soft tissue > Uncertain differentiation > NUTM1 rearranged sarcoma

by Divya Bansal, M.B.B.S., M.D., Sunil Pasricha, M.B.B.S., M.D.

Topic summary: NUTM1 rearranged sarcoma is an emerging group of aggressive soft tissue sarcomas defined by chromosomal rearrangements involving the NUTM1 (NUT midline carcinoma family member 1) gene on chromosome 15q14, distinct from the more well known NUT carcinoma. Extremely rare entity. Rapidly growing, usually deep seated, often painful or palpable mass. Most common in the somatic soft tissues, thoracic region, gastrointestinal tract and body cavity. Metastasis is seen in 50% of adult cases at presentation; overall survival: 13.4 months.

Featured Image

Topic full text: MALT lymphoma of the dura

Authors: Giovanni Martino, M.D., Flavia Adotti, M.D., Antonio d'Amati, M.D., Martina Mandarano, M.D., Ph.D., Marco Gessi, M.D. · Editorial Board Member: Jared T. Ahrendsen, M.D., Ph.D. · Last staff update: 6 October 2026 (update in progress)

Definition / general

• Extranodal, dural based, low grade B cell lymphoma of mucosa associated lymphoid tissue (MALT)
• Can have plasmacytic differentiation

Essential features

• Small to medium sized marginal zone B cell lymphoma arising in the dura
• B cell phenotype (CD20, CD79a) nonspecific for other lymphoma subtypes
• Usually, plasmacytic differentiation with monotypic plasma cell component
• Indolent clinical course; most patients benefit from local treatment strategies

Terminology

• Extranodal marginal zone lymphoma of mucosa associated lymphoid tissue
• MLD (MALT lymphoma of the dura)

ICD coding

• ICD-O: 9699/3 - MALT lymphoma of the dura
• ICD-10: C88.4 - extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT lymphoma)
• ICD-11: 2A85.3 - extranodal marginal zone B cell lymphoma, primary site excluding stomach or skin

Epidemiology

• Rare disease; incidence unknown (Acta Neurol Belg 2023;123:1189)
• Adult, median age = sixth decade
• M:F = 1:5 - 7 (WHO)
• Marginal zone lymphoma (MZL) is the most common lymphoma of the dura
• More common than intraparenchymal MALT lymphoma (Clin Lymphoma Myeloma Leuk 2018;18:34, Cancer Med 2020;9:663)

Sites

• Dural based
• Intracranial dura most commonly
• Extracranial dura (spinal cord) less frequently (Mod Pathol 2011;24:355, Am J Clin Pathol 2020;154:124)
• Multifocal disease reported in ~23% of patients; systemic recurrence is uncommon (Leuk Lymphoma 2017;58:882)

Pathophysiology

• Unlike other extranodal marginal zone lymphomas, no known pathogenetic mechanism has been described in this setting to date
• Mutations in TNFAIP3, NOTCH2 and TBL1XR1 genes, along with other chromosomal aberrations, have been reported (see Molecular / cytogenetics description) (Oncotarget 2016;7:43052)

Etiology

• Still not completely known
• Correlation with chronic inflammation has not yet been demonstrated (unlike MALT lymphomas of other sites, e.g., gastric)
• Onset of this disease in the setting of multiple sclerosis, Chlamydia psittaci infection and hepatitis C have been reported in single cases (Leuk Res 2012;36:e155, Hum Pathol 2011;42:738, World J Oncol 2020;11:122)

Clinical features

• Compression symptoms; most commonly
  • Headache
  • Seizures
  • Focal neurological defects
• References: Hum Pathol 2025;156:105683, Cancer 2020;126:2811

Diagnosis

• Diagnosis requires histological examination (J Clin Oncol 2005;23:5718)
• WHO 5th edition diagnostic criteria
  • Essential: dural based, marginal zone-like features and B cell markers with follicular dendritic cells (FDC) meshwork (CD21 / CD23 / CD35+)
  • Desirable: FISH analysis and gene rearrangement clonality assay, if not already demonstrated with immunophenotype

Laboratory

• Cerebrospinal fluid may show neoplastic cells in case of leptomeningeal infiltration (Neurology 2006;66:1763)

Radiology description

• MRI findings (Neurology 2006;66:1763)
  • Single or multiple plaque-like thickening of the dura
  • Can mimic meningioma
  • Extra-axial lesions show gadolinium enhancement
  • Underlying parenchymal vasogenic edema, hyperostosis or bone erosion have been reported

Prognostic factors

• Good prognosis with complete remission (better than parenchymal based MZL) (Am J Clin Pathol 2020;154:124)
• 3 year progression free survival: 89% (Leuk Lymphoma 2017;58:882)

Case reports

• 42 year old woman with positive history of MZL of the parotid gland, developed intracranial relapse 4 years later (Acta Neurol Belg 2023;123:1189)
• 49 year old woman with primary MZL of the dura mimicking meningioma (Surg Neurol Int 2024;15:113)
• 52 year old woman with primary MZL of the dura, initially misdiagnosed as meningioma, confirmed after progression and craniotomy (Acta Neurol Belg 2023;123:1189)
• 63 year old woman with massive kappa light chain amyloidosis associated with MZL of the dura (J Neurosurg 2002;96:368)
• 66 year old woman presented with 2 simultaneous intracranial MZL, located in 2 different regions (Front Oncol 2023;12:927086)
• 83 year old woman with MZL of the dura and lymphomeningothelial lesions (Int J Surg Pathol 2023;31:879)

Treatment

• Local treatment strategies usually preferred over systemic treatment (J Clin Oncol 2005;23:5718)
• Surgical resection
• Adjuvant radiation or chemotherapy in variable combination (Clin Lymphoma Myeloma Leuk 2018;18:34, Cancer 2020;126:2811)

Gross description

• See Radiology description

Frozen section description

• Intraoperative frozen section may be helpful in exclusion of more aggressive neoplasms or meningioma
  • Small mature lymphocytes are typically observed with or without plasmacytic differentiation
  • Few or no mitoses are reported

Microscopic (histologic) description

• Mass forming proliferation of small lymphocytes (Am J Clin Pathol 2020;154:124)
• Morphology (J Clin Oncol 2005;23:5718, Leuk Lymphoma 2017;58:882)
  • Prominent plasmacytic differentiation
  • Monocytoid appearance (clear cytoplasm)
• Growth patterns
  • Vaguely nodular
  • Diffuse
• Reactive germinal centers variably present
  • Follicular colonization may be observed
• Small amount of large cell (< 5%)
• Plasma cell component (usually in limited quantity in comparison to parenchymal based MZL) (Am J Clin Pathol 2020;154:124)
• Entrapped meningothelium
• Rarely, Virchow-Robin spaces and brain parenchyma infiltration
• Occasional light chain amyloidosis (J Clin Oncol 2005;23:5718)

Microscopic (histologic) images

Contributed by Giovanni Martino, M.D. and Martina Mandarano, M.D., Ph.D.

Cytology description

• Varying numbers of mature lymphocytes, lymphoplasmacytes and plasma cells are observed in tissue smears; in some cases, nuclear inclusions such as Dutcher bodies are reported and may be a clue for diagnosis
• Most reported cases show no or very limited cerebrospinal fluid involvement; therefore, cerebrospinal fluid cytology examination may be of limited value in this lymphoma (Am J Clin Pathol 2020;154:124)

Positive stains

• B lineage marker: CD20, CD79a (J Clin Oncol 2005;23:5718)
• MUM1 / IRF4 (variable)
• BCL2
• Kappa and lambda chains: to highlight eventual light chain restriction
• Low proliferation index (Ki67) (Clin Lymphoma Myeloma Leuk 2018;18:34)
• As in primary cutaneous MZL (PCMZL), plasma cells are often IgG4+ (without IgG4 related disease) (Mod Pathol 2011;24:355)
• CD21, CD23 and CD35 to point out the possible presence of disrupted follicular dendritic cell meshwork (follicular colonization)
• Congo red can reveal the amyloid deposition (apple green birefringence) (J Neurosurg 2002;96:368)
• References: Cancer 2020;126:2811, Hum Pathol 2025;156:105683

Negative stains

• CD5, CD23, cyclin D1, CD10, BCL6 (J Clin Oncol 2005;23:5718)
• EBER (J Clin Oncol 2005;23:5718)
• Cytokeratins
• PR, SSTR2A
• STAT6, S100, MelanA, PRAME, SOX10

Molecular / cytogenetics description

• IG genes clonality assays to confirm the clonal nature of the proliferation
• Overall, similar genomic landscape of other MZL subtypes, except chromosome 3 and 18 are less frequently involved (Oncotarget 2016;7:43052)
• Characteristically, mutually exclusive genetic alterations correlate with distinct morphophenotypes
  • Monoallelic and biallelic inactivation of TNFAIP3 are more common in cases exhibiting plasmacytic differentiation, including 3 IgG4+ cases (Oncotarget 2016;7:43052)
  • Activating NOTCH2 mutations are mostly reported in cases with monocytoid appearance
  • NOTCH2 mutated cases generally display also inactivating TBL1XR1 mutations
• Other recurrent mutations in KLHL6 and MLL2
• Chromosomal aberrations such as losses at 1p36.32 (encompassing TNFRSF14, PRDM16, RPL22 and CAMTA1 genes) and gains at 6p25.3 (covering the IRF4 gene)
• IGH::MALT1 fusion [t(14;18)(q32;q21)] has been reported in 1 case (J Hematop 2008;1:131)

Sample pathology report

• Dural based lesion, CNS (e.g., frontal lobe), biopsy / excisional surgery:
  • Localization of mature B cell neoplasm with plasmacytic differentiation, consistent with extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (see comment)
  • Comment: Staging workup (imaging and bone marrow biopsy) is recommended to exclude systemic disease and to confirm primary dural localization.

Differential diagnosis

• With other small to medium B cell lymphomas, such as (J Neurosurg 2002;96:368, J Clin Oncol 2005;23:5718):
  • Lymphoplasmacytic lymphoma:
    • Morphophenotype overlaps; IgM monoclonal component and MYD88 L265P mutation required
  • Chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL):
    • CD5+ / CD23+, usually lymphocytosis
  • Mantle cell lymphoma:
    • Cyclin D1+, SOX11+
  • Follicular lymphoma:
    • CD10+ / BCL6+
• Plasma cell neoplasms in cases of extreme plasmacytic differentiation:
  • Differential diagnosis can be very tricky, although isolated extraosseous plasma cell neoplasms are very rare
  • FISH analyses may be helpful to distinguish the different diseases (Semin Diagn Pathol 2025;42:150944)
• Meningiomas:
  • In selected cases, radiologic features like contrast enhancement, bone erosion and the absence of calcification may be helpful in the diagnosis of lymphoma (Neuroradiology 2021;63:1215)
  • Histology is mandatory for a certain diagnosis
• IgG4 related disease in its lesion forming variant, when a prominent plasmacytic component is reported:
  • In these cases, the IgG4 / IgG ratio should be carefully evaluated, as in the IgG4 related disease consensus guidelines (Mod Pathol 2012;25:1181)
  • Plasma cells in IgG4 related disease are polyclonal
  • Cases with oligoclonal or monoclonal plasma cells should be carefully evaluated with clinical and serological data, as an overlap between MALT lymphoma and IgG4 related disease has been reported in rare cases
• Meningeal melanoma or metastatic dissemination of cutaneous melanoma:
  • Some cases may be considered in cases of plasmacytoid-like morphological variants; in these cases, an appropriate immunohistochemical panel is mandatory to render the correct diagnosis
• In selected cases, a differential diagnosis with dural based solid tumors should be considered:
  • Hypercellular solitary fibrous tumor (SFT):
    • Hypercellular SFT may be diagnosed with STAT6 immunohistochemistry and a careful examination of the stromal component
  • Small cell sarcomas, such as Ewing sarcoma:
    • May also be considered
    • Immunohistochemical (e.g., CD99) and appropriate molecular testing are mandatory to correctly render the diagnosis

Additional references

• WHO Classification of Tumours Editorial Board: Haematolymphoid Tumours, 5th Edition, 2024

Practice question #1

Which of the following histologic findings is most characteristic of marginal zone lymphoma (MZL) of the dura?

1. Diffuse brain parenchymal invasion
2. Extensive coagulative necrosis
3. Follicular colonization by neoplastic marginal zone B cells
4. High grade cytologic atypia with brisk mitotic activity
5. Perivascular pseudorosettes

Practice answer #1

C. Follicular colonization by neoplastic marginal zone B cells. Follicular colonization is a well recognized feature of MZL and may be seen in dural cases. Answer D is incorrect because dural MZL is a low grade lymphoma with bland cytology and low mitotic activity. Answer B is incorrect because extensive necrosis is not a typical finding and should prompt consideration of a different diagnosis. Answer A is incorrect because the tumor usually remains confined to the dura and lacks significant brain parenchymal invasion. Answer E is incorrect because perivascular pseudorosettes are characteristic of ependymoma and are not seen in MZL.

Reference: MALT lymphoma of the dura

Practice question #2

Histologic examination of a dural based lesion shows small mature lymphocytes with plasmacytic differentiation and residual reactive germinal centers infiltrated by marginal zone cells. Which histologic finding is demonstrated in the image above?

1. Diffuse large B cell lymphoma
2. Follicular colonization
3. Follicular lymphoma
4. Geographic necrosis
5. Starry sky pattern

Practice answer #2

B. Follicular colonization. The image shows residual reactive germinal centers infiltrated and partially replaced by marginal zone B cells, a characteristic feature of marginal zone lymphoma. Answer C is incorrect because follicular lymphoma is a distinct B cell lymphoma characterized by a neoplastic follicular growth pattern and typically expresses CD10 and BCL6. Answer D is incorrect because geographic necrosis is not present and is uncommon in this indolent lymphoma. Answer A is incorrect because diffuse large B cell lymphoma is composed of sheets of large atypical lymphoid cells, which are not seen in this image. Answer E is incorrect because a starry sky pattern is characteristic of highly proliferative lymphomas, particularly Burkitt lymphoma, and is not present in this lesion.

Reference: MALT lymphoma of the dura