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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5192_Библиотеки_им_академика_М_И_Перельмана.pdf
6.7 Neural Neoplasms
Antoni B myxoid area
Verocay body
Antoni A spindle cells
Fig. 6.25 Schwannoma (high mag). (From Rapini RP. Neural neoplasms. In: Practical Dermatopathology. 2nd ed. Philadelphia: Elsevier; 2012:367–377.)
■
Degenerative atypia is present in “ancient
schwannomas” (benign)
■
Boards tip: almost never see epidermis in biopsy
specimen since so deeply seated (typically appears
“shelled-out”)
• 10% of cases are bilateral acoustic neuromas seen in NF2
patients
Neurobroma (NF)
• Benign proliferation of Schwann cells 1 other nerve
components (broblasts, perineurial cells, intermediate
cells, and axons)
• Flesh-colored soft nodule w/ “buttonhole sign”
• Histology: dermal location; not as well-circumscribed as
PEN; wavy “buckled” nuclei; cells haphazardly arranged;
loose, myxoid stroma with ↑ mast cells and thin, wavy
collagen bers
■
S1001, neurolaments1
• 10% have multiple lesions → raises concern for NF1
• Plexiform neurobromas (“bag of worms”):
pathognomonic of NF1; ↑ risk of transformation to
malignant peripheral nerve sheath tumor (MPNST)
Nerve sheath myxoma (“neurothekeoma”)
• Formerly called “neurothekeoma” or “myxoid
neurothekeoma” → terms have been abandoned and
replaced by “nerve sheath myxoma” (preferred current
name)
• Soft skin-colored nodule; most commonly hands/ngers
of 40- to 50-year-old adults
• Histology: plexiform proliferation of discrete myxoid
lobules containing bland spindle cells
■
S1001 (unlike cellular neurothekeoma) (Fig. 6.26)
Cellular neurothekeoma
• Benign neoplasm; uncertain histogenesis
• Firm, pink papules on face of young adults (20–30 years
old); F . M
Fig. 6.26 Nerve sheath myxoma: the tumor is composed of discrete lobules
separated by brous septa. (From Calonje E, Damaskou V, Lazar AJ. Connective
tissue tumors. In: Calonje E, Brenn T, Lazar AJ, Billings SD, eds. McKee’s
Pathology of the Skin . 5th ed. Philadelphia: Elsevier; 2020:1698–1894.)
• Histology: dermal proliferation; nests and fascicles of
epithelioid cells (cells resemble Spitz nevus cells or
sarcoidal histiocytes)
■
Boards favorite: always S100 negative (vs. classic
“neurothekeoma”); but S100A61, NKI/C31, and PGP
9.51
Granular cell tumor
• Benign (malignant in 1%); neural-crest/Schwann cell
derived
• Most common in adults (particularly females and African
Americans)
• 90% solitary; rm asymptomatic nodule; tongue (#1),
but any site affected
• Histology: pseudoepitheliomatous hyperplasia overlying
an ill-dened dermal proliferation of large polygonal cells
with abundant pink, granular cytoplasm and a small
365
CHAPTER 6 • Neoplastic Dermatology
Fig. 6.27 Granular cell tumor. The tumor cells are large with abundant eosinophilic cytoplasm and uniform vesicular nuclei. (From Brinster NK, Liu V, Diwan H,
McKee PH. Granular cell tumor. In: Dermatopathology: A Volume in the High
Yield Pathology Series. Philadelphia: Elsevier; 2011:510–511.)
nucleus, pink cytoplasmic inclusions (pustulo-ovoid
bodies of Milian 5 aggregated lysosomes) (Fig. 6.27)
■
S1001
■
Boards favorite: if see SCC-like epidermal changes →
look in dermis for granular cell tumor!
Malignant peripheral nerve sheath
tumor (MPNST)
• Presents as a rapidly growing nodule within a plexiform
neurobroma (lifetime risk 5 2%–13%); may have a
large overlying CALM
• Histology: densely cellular proliferation of atypical
spindle cells often with large areas of necrosis
(“geographic necrosis”) and a high mitotic rate
■
Often only focally S1001
Merkel cell carcinoma (MCC)
• Aggressive malignant neoplasm (deadlier than
melanoma); most common in elderly on head/neck;
UV exposure is major risk factor; ↑ risk w/
immunosuppression
• Erythematous to violaceous papulonodule which grows
rapidly and has high propensity for metastasis (LN
metastasis 5 50%; distant metastasis 5 33%)
• Pathogenesis: Merkel cell polyomavirus (MCPyV)
implicated in 80% of cases in the United States and
Europe; UVR also plays a major role
■
MCPyV integrates into host genome → oncogene
expression, Rb inhibition → cell proliferation
MCPyV1: ↓ mutational burden and ↓ UV-signature
mutations (vs. MCPyV
recurrence risk)
■
UVR → inactivating mutations in p53 and other tumor
suppressor genes
• Histology: inltrative or nodular dermal/subcutaneous
mass composed of sheets of uniform basaloid cells with
high N:C ratio and nely speckled “salt-and-pepper”
tumors, which have higher
chromatin (usually without prominent nucleoli);
numerous mitoses (often . 30/mm
2
) and apoptotic
cells
■
Positive stains: CK20 (paranuclear dot pattern, highly
sensitive), neurolaments (paranuclear dot pattern,
highly sensitive), chromogranin/synaptophysin, NSE,
EMA, and CD56; MCPyV1 (80%)
■
Negative stains: TTF-1, CK7, S100, and CEA
• Histologic DDx
■
Small cell lung carcinoma (main consideration!): TTF11 and CK71; negative for CK20 and neurolaments
(lacks dot pattern)
■
Lymphoma: caution because MCC usually expresses
PAX-51 (80%–90%) and TdT1 (70%)
• Prognostic factors a/w poor outcomes
■
Clinical: male, immunosuppression, older age, head/
neck location, diameter . 2 cm, SLNB1
■
Histological: p631, inltrative (vs. nodular) growth
pattern, lymphovascular invasion (detected via H&E or
D2-40 immunostain), ↑ mast cell burden on histology,
MCPyV
(debatable)
• NCCN Workup and Treatment Guidelines
■
Initial workup
Given the high risk of MCC, additional initial
workup warranted and includes:
♦ H&P, complete skin and LN exam
♦ Imaging is encouraged in most cases (whole-
body PET with fused axial imaging may be most
sensitive for detecting metastasis at baseline)
♦ Consider quantication of serum MCPyV
oncoprotein antibodies
♦ If immunosuppressed, consider modication/
reduction of immunosuppression
■
Clinically node negative (N0)
Treatment
♦ No baseline risk factors → excision with 1 to
2 cm margins and SLNB
If clear margins, negative SLNB, and no
adverse risk factors → observe
If positive margins or other adverse risk factors
on excision specimen → re-excision or RT
♦ One or more baseline risk factor → excision with
individualized margins, SLNB, and adjuvant RT
with multidisciplinary consultation
Baseline risk factors for MCC include:
Tumor size . 1 cm
Chronic T-cell immunosuppression, HIV,
CLL, SOTR
H/N primary site
Lymphovascular invasion
♦ SLNB negative
Observe if low risk
Consider RT to nodal basin in high-risk
patients at increased risk for false-negative
SLNB
♦ SLNB positive
Node dissection and/or radiation AND
adjuvant systemic therapy (preferably in a
clinical trial, typically PD-1/PD-L1 inhibitors)
♦ Recurrent locally advanced MCC → consider
pembrolizumab
366
6.8 Smooth Muscle Neoplasms
■
Clinically node positive (N1)
Workup
♦ Imaging
♦ FNA or core biopsy
If negative → excisional biopsy of LN or
radiographic surveillance
Treatment
♦ If node positive (N1) and no disseminated
metastasis (M0) on workup:
Node dissection and/or radiation AND
adjuvant systemic therapy (preferably in a
clinical trial, typically PD-1/PD-L1 inhibitors)
■
Disseminated MCC (M1)
Treatment (clinical trial preferred)
♦ Consider any of the following therapies or
combinations of:
Systemic therapy
Typically, PD-1/PD-L1 inhibitors such as
avelumab, pembrolizumab, nivolumab
RT
Surgery
Palliative/supportive care
Primitive neuroectodermal tumor
(neuroblastoma)
• Third most common childhood malignancy
• Tumor of primitive neural crest cells of sympathetic
nervous system → adrenal gland or retroperitoneum
most common sites
■
In skin, usually metastatic although rarely can be
primary
• Clinical:
■
75% have metastatic disease at the time of diagnosis
■
Cutaneous metastases are presenting sign in 30% w/
metastatic disease → p/w multiple blue nodules on
trunk and extremities
■
Peripheral blanching after stroking lesion, due to
catecholamine release
■
“Raccoon eyes” (periorbital darkening/purpura) from
orbital metastases
■
↑ Urinary catecholamines (.90%)
■
Infants , 1 year old → favorable prognosis; older
children → poor prognosis
• Histology: dermal or subcutaneous nodule composed of
small, round, blue cells
■
NSE1 and neurolaments1 → favors neuroblastoma
over other small round blue cell tumors (lymphoma,
MCC, small cell lung carcinoma, Ewing sarcoma)
■
FISH for n-Myc aids in diagnosis and is a/w worse
prognosis
■
Pseudo Darier sign: stroking of lesion → becomes red,
painful, and elevated (as a result of contraction of
smooth muscle)
• Multiple lesions can occur as part of Reed syndrome (AD
inheritance, fumarate hydratase mutations, multiple
cutaneous and uterine leiomyomas and RCC) (Fig. 6.28)
• Histology: ill-dened dermal proliferation of haphazardly
arrayed, intersecting fascicles of smooth muscle cells
(spindle cells with bright pink cytoplasm and “cigar-
shaped” nuclei); lacks mitotic activity (Fig. 6.29)
■
Stains: desmin1, SMA1, and caldesmon1; smooth
muscle bers are pink-red with Masson trichrome stain
Fig. 6.28 Leiomyoma. Numerous grouped leiomyomata in a middle-aged
woman manifesting as tender erythematous papules on the trunk. (From Brinster
NK, Liu V, Diwan H, McKee PH. Leiomyoma and angioleiomyoma. In: Dermato-
pathology: A Volume in the High Yield Pathology Series . Philadelphia: Elsevier;
2011:523–524.)
6.8 SMOOTH MUSCLE NEOPLASMS
Pilar leiomyoma
• Benign proliferation of smooth muscle arising from
arrector pili
• Red-brown papules on trunk or extremities
■
Painful, especially with cold exposure
Fig. 6.29 Pilar leiomyoma. The reticular dermis is replaced by interlacing bundles
of smooth muscle cells (H&E). (From Patterson JW. Tumors of muscle, cartilage,
and bone. In: Weedon’s Skin Pathology. 4th ed. Philadelphia: Elsevier, 2016:
1029–1040.)
367
CHAPTER 6 • Neoplastic Dermatology
• Histologic DDx:
■
Smooth muscle hamartoma/Becker’s nevus: fewer and
more discrete smooth muscle bundles interspersed in
normal dermal collagen
■
Angioleiomyoma: larger and deeper; smooth muscle
bundles circumferentially arrayed around collapsed
vessels
• Treatment: excision if solitary; if multiple → gabapentin
or nifedipine (reduces smooth muscle contraction)
Genital Leiomyoma
• Solitary lesions on the vulva, scrotum, and areola arising
from supercial network of smooth muscle found at these
sites; asymptomatic
• Histology: similar to pilar leiomyomas, but often larger,
less sharply circumscribed, and may have mitoses
Angioleiomyoma
• Benign proliferation derived from smooth muscle in wall
of subcutaneous vessels
• Most commonly middle-aged females on lower
extremity; frequently painful (Box 6.2)
• Histology: subcutaneous, well-circumscribed nodule w/
compact fascicles of smooth muscle cells circularly
arrayed around vessels with collapsed (“slit-like”) lumens
(Fig. 6.30)
■
Is a proliferation of muscle in vessel wall, not a
proliferation of endothelial cells → central vascular
lumens are compressed by muscular wall → “slit-like”
lumens surrounded by a ton of circularly arrayed
smooth muscle
■
Stains: desmin1 (differentiates from myopericytoma),
SMA1, calponin1 and h-caldesmon1
Leiomyosarcoma (LMS)
• LMS divided into supercial and deep forms:
■
Deep LMS (subfascial variant): almost never
encountered by dermatologists (→ not discussed
further); deep soft tissue sarcoma; often arises
from smooth muscle walls of large vessels; usually
fatal
■
Supercial LMS (suprafascial variant): most relevant
variant for dermatologists; arises from arrector pili or
genital/areolar smooth muscle; generally good
prognosis
Dermal LMS: most behave in indolent fashion,
and some experts have argued they are not true
malignancies; however, a 2014 study from Mayo
Clinic reported a 10% metastatic rate with dermal
LMS
Subcutaneous LMS: arises from vascular smooth
muscle; behaves more aggressively than dermal
LMS → ↑ risk of metastases (esp. if diameter
. 5 cm)
• Red-brown nodules or plaques; most common on
extremities
• Histology: ranges from low-grade (resemble leiomyoma,
but have ↑ cellularity, ↑ mitotic activity, and
pleomorphism) to high-grade lesions (AFX-like)
■
Stains: desmin1 and SMA1
Box 6.2 Mnemonic: Painful Skin Lesions
“BANGLE(S)”
Blue rubber blebs
Angiolipoma
Neuroma
Glomus tumors
Leiomyoma
Eccrine Spiradenoma
Fig. 6.30 Angioleiomyoma. (From Patterson JW. Tumors of muscle, cartilage,
and bone. In: Weedon’s Skin Pathology. 5th ed. Philadelphia: Elsevier, 2021:
1081–1092.)
6.9 HEMATOLYMPHOID NEOPLASMS
Mycosis fungoides (MF)
Epidemiology
• Accounts for 50% of all primary cutaneous lymphomas
• Most common type of cutaneous T-cell lymphoma
• Onset typically in sixth or seventh decade, but can occur
in younger patients including children
Clinical features (Table 6.6)
• Progression though patch, plaque, and tumor stages
• Patch stage: irregular erythematous scaly patches occurring
in non–sun-exposed/bathing suit distribution; may be
pruritic (Fig. 6.31A)
• Plaque stage: well-demarcated variably shaped violaceous
to red-brown plaques; may be pruritic
• Tumor stage: rapidly enlarging nodules with frequent
ulceration; arises in a background of patch and plaque
lesions (otherwise unlikely to be MF) (Fig. 6.31B)
• Rare LN and visceral involvement
Histology
• Patch stage: epidermotropic atypical lymphocytes
(enlarged w/ cerebriform, hyperchromatic nuclei)
predominantly in the epidermis in clusters (Pautrier
368
6.9 Hematolymphoid Neoplasms
Table 6.6 Cutaneous T-Cell Lymphoma Staging
Stage T N M B
IA
IB
IIA T1 or T2 N1: no dermatopathic histological evidence of MF
IIB
IIIA
IIIB T4 N0-N2 M0
IVA1 T1-T4 N0-N2 M0
IVA2 T1-T4 N3: lymph nodes involved w/ loss of normal
IVB T1-T4 N0-N3 M1: metastasis B0-B2
B, Blood; BSA, body surface area; M, metastasis; MF, mycosis fungoides; N, node; T, tumor.
T1: ,10% BSA
T1a: patches
T1b: plaques
T2: .10% BSA
T2a: patches
T2b: plaques
T3: tumors (lesions . 1 cm
diameter w/ deep infiltration)
T4: erythroderma (.80% BSA)
N0: no palpable nodes or histologic evidence of MF M0: no visceral
involvement
N0 M0 B0-B1
M0 B0-B1
N1a: clone-negative
N1b: clone-positive
N2: early involvement with MF, aggregates of atypi-
cal cells with preservation of nodal architecture
N2a: clone-negative
N2b: clone-positive
N0-N2 M0 B0-B1
N0-N2 M0 B0
M0 B0-B2
architecture
B0: ,5% peripheral lymphocytes
atypical
B0a: clone-negative
B0b: clone-positive
B1: .5% of lymphocytes atypical
but , 1000/mL
B1a: clone-negative
B1b: clone-positive
B1: .5% of lymphocytes atypical but
,1000/mL
B2: .1000/mL circulating atypical
lymphocytes (Sézary cells)
A
Fig. 6.31 Mycosis fungoides. (A) Patch stage. (B) Tumor stage. (From James WD, Elston DM, McMahon PJ. Cutaneous lymphoid hyperplasia, cutaneous T-cell lymphoma, other malignant lymphomas, and allied diseases. In: Andrews’ Diseases of the Skin Clinical Atlas. Philadelphia: Elsevier; 2018:501–516.)
microabscesses) and lined up at DEJ with clear halos
surrounding the cells; supercial dermal band-like/
“lichenoid” lymphocytic inltrate (predominantly
reactive lymphocytes); “wiry” papillary dermal brosis
(Fig. 6.32)
B
■
Clue to epidermotropism (vs. exocytosis) 5
intraepidermal lymphocytes out of proportion to the
degree of spongiosis
• Plaque stage: more prominent epidermotropism w/ more
atypical lymphocytes in the dense dermal band-like inltrate
369
CHAPTER 6 • Neoplastic Dermatology
Fig. 6.32 Mycosis fungoides. There is a band-like dermal inltrate with atypical
lymphocytes in the basal epidermis (H&E). (From Patterson JW. Cutaneous inltrates—lymphomatous and leukemic. In: Weedon’s Skin Pathology . 5th ed.
Philadelphia: Elsevier, 2021:1225–1272.)
• Tumor stage: ↑ density and depth of dermal inltrate of
atypical lymphocytes with decreased/absent
epidermotropism
■
Large cell transformation dened by . 25% large cells
(.4 times the size of a mature lymphocyte) 1/– CD30
expression (often present, but not required for
diagnosis; CD30 negative a/w poor prognosis)
• Immunophenotype:
■
Typical phenotype: CD31/CD41/CD8 mature T
lymphocytes
■
Variable loss of pan T-cell markers: CD7 loss (most
common, least specic) . CD5 and CD2 loss (less
common, more specic)
• Histologic features are often ambiguous in early patch
stage → molecular testing for T-cell receptor gene
rearrangement (TCR-GR) may be useful, but has pitfalls!
■
False positives: clonal rearrangements detected in some nonneoplastic inammatory dermatoses (including eczema) →
must correlate w/ clinical and histologic ndings
■
False negatives: common in very early patch stage
• Hypopigmented MF (variant): favors darkly pigmented
patients; more common presentation in young patients;
usually CD4 /CD81→ cytotoxic phenotype → a/w more
interface changes (apoptotic keratinocytes and pigment
incontinence) → explains hypopigmentation seen clinically
advanced MF and Sezary patients, but a/w high mortality
and recurrence) represent other treatment options
Clinical variants
• Folliculotropic: 10% of patients; head/neck area a/w
papules/acneiform lesions (early) to plaques with
alopecia (advanced) (Fig. 6.33); histology: atypical
inltrates involve follicular epithelium 1 follicular
mucinosis; ↑ depth makes it more refractory to
treatment → worse prognosis (similar to tumor stage
MF), sustained remission is rare
• Pagetoid reticulosis (Woringer-Kolopp disease): rare,
progressive solitary psoriasiform plaque on distal
extremities; histology: very prominent epidermotropism
in a pagetoid pattern; good prognosis
• Granulomatous slack skin: extremely rare; sagging skin
folds in the axilla/groin; granulomatous inammation w/
multinucleated giant cells, atypical lymphocytes, and
prominent elastophagocytosis (→ loss of elastic recoil);
indolent course; usually evolves to classic MF; up to 30%
develop Hodgkin lymphoma
Sézary syndrome
• Erythroderma (intensely pruritic); lymphadenopathy and
neoplastic Sézary cells in the skin, blood, and LNs;
considered distinct from MF
• Must demonstrate a circulating population of CD4
1
neoplastic T-cells with an absolute count . 1000 cells/mL or
expanded CD4
1
CD4
/CD7- cells $ 40% or CD41/CD26 cells $ 30%
1
T-cell population n CD4/CD8 ratio $ 10,
• Histologic features may be nonspecic or resemble MF
(often more spongiosis, less epidermotropism than typical
MF); CD4
1
/8 , PD-11, TOX1, KIRDL21
• Treatment: ECP 1 systemic therapies (e.g., bexarotene);
chemotherapy, mogamulizumab, and alemtuzumab for
worse cases; poor prognosis
Adult T-cell leukemia/lymphoma (ATLL)
• a/w HTLV-1 virus → endemic in areas with high virus
prevalence (Japan, Caribbean, Central Africa)
• p/w leukemia, lymphadenopathy, organomegaly,
hypercalcemia, and skin lesions; poor prognosis
Treatment
• Patch/plaque stage: topical/intralesional steroids, topical
nitrogen mustard/mechlorethamine, topical bexarotene/
alitretinoin, and phototherapy, (NB UVB for patch and PUVA)
• Can add methrotrexate (MTX) or pralatrexate, oral
acitretin or bexarotene for progressive disease
• More advanced disease: histone deacetylase inhibitors
(vorinostat, romidepsin, resminostat), brentuximab
vedotin (anti-CD30 antibody) for transformed MF,
mogamulizumab (anti-CCR4 antibody; useful because
MF homes to skin using CCR4)
• Systemic chemotherapy (e.g., CHOP, gemcitabine,
doxorubicin): reserved for advanced/rapidly progressive
disease, ↑ risk of secondary infections; radiotherapy (local
if few tumors vs. total skin electron beam for generalized
plaques/tumors), ECP (for erythrodermic MF), and
allogeneic stem cell transplant (effective for some
370
Fig. 6.33 Alopecia mucinosa. (From James WD, Elston DM, Treat JR, Rosenbach
MA, Neuhaus IM. Cutaneous lymphoid hyperplasia, cutaneous T-cell lymphoma,
other malignant lymphomas, and allied diseases. In: Andrews’ Diseases of the
Skin. 13th ed. Philadelphia: Elsevier; 2020:731–749.)
6.9 Hematolymphoid Neoplasms
• Histopathology resembles MF, but has characteristic
“oret” or “clover-leaf” malignant T cells
■
Immunophenotype: CD41/CD8 /CD251, PD-1
1
Lymphomatoid papulosis (LyP)
• CD301 lymphoproliferative disorder, along with ALCL
(see below) and “borderline” cases—this group of
A
disorders are indolent with recurrences but good
prognosis overall
• Any age, but favors adults in 40s (vs. PLEVA, which favors
children); multiple (10–20 lesions usually), recurrent,
ulcerative, and red-brown papulonodules on trunk and
extremities → individual lesions self-resolve in 1 to
2 months → heals w/ atrophic varioliform scars
(Fig. 6.34A)
Erythrocytes in epidermis
Edematous dermal papilla
Localized papule of
lymphocytes
Eosinophil
Neutrophil
Atypical lymphocytes
Erythrocyte
B
C
Fig. 6.34 Lymphomatoid papulosis. (A) Clinical presentation with varied skin lesions (e.g., papules, pustules, necrotic lesions) in different stages of evolution. (B) and
(C) Diffuse inltrate, extending into the dermis, with atypical lymphocytes, as well as some neutrophils and neutrophils. ( A, From James WD, Elston DM, McMahon PJ.
Cutaneous lymphoid hyperplasia, cutaneous T-cell lymphoma, other malignant lymphomas, and allied diseases. In: Andrews’ Diseases of the Skin Clinical Atlas
Philadelphia: Elsevier; 2018:501–516. B and C, From Rapini RP. Myeloproliferative disorders. In: Rapini RP, ed. Practical Dermatopathology. 3rd ed. Philadelphia:
Elsevier; 2021:341–364.)
371
CHAPTER 6 • Neoplastic Dermatology
• Histology (all histological variants have the same clinical
presentation)
■
Type A (75%; most classic form, most important for
Boards): wedge-shaped inltrate with clusters of large,
atypical, Reed-Sternberg-like CD301 (Ki-1)
lymphocytes, ↑ mitotic activity and atypical mitoses,
mixed inammation (lymphocytes, eosinophils, and
neutrophils); overlying ulceration and parakeratotic
scale (see Fig. 6.34B and C)
■
Type B (MF-type, 10%–15%): histologically resembles
patch/plaque MF; epidermotropic inltrate of small,
hyperchromatic, cerebriform CD41 cells; CD30 usually
negative (rarely see large CD301 cells in this variant)
■
Type C (ALCL-type, 10%): dense pan-dermal inltrate
with sheets of CD41/CD82/CD301 large lymphocytes;
histologically indistinguishable from anaplastic large
cell lymphoma (ALCL) and large cell transformation
of tumor-stage MF → need clinical correlation
■
Type D (epidermotropic CD81 variant, ,5%):
abundant epidermotropic CD4-/CD81/CD301 cells;
histologically resembles aggressive epidermotropic
T-cell lymphoma, but has much better prognosis →
need clinical correlation to ensure correct diagnosis;
also could confuse histologically with pagetoid
reticulosis (very different clinical presentation)
■
Type E (angioinvasive LyP; ,5%): Angiodestructive
clusters of small-medium CD4
2
/CD81/CD30
1
lymphocytes, along with brinous vasculitis/thrombi;
histologically resembles extranodal NK/T-cell
lymphoma,
■
Type 6p25.3 (chromosomal rearrangement of DUSP22-
gd-TCL, angioinvasive ALCL
IRF4): Biphasic growth pattern 5 small cerebriform
lymphocytes in epidermis and dense collections of
large, atypical lymphocytes in dermis; CD4
1
CD30
immunophenotype
2
/CD82/
• TCGR clonal rearrangement in 40%–90% (not correlated w/
biologic behavior); identical clones may be demonstrated in
peripheral blood of patients with severe disease
• Excellent prognosis (.99% disease-specic survival;
overall survival at 10 years 5 92%)
• Up to 25% of LyP patients have an associated malignant
lymphoma (MF . Hodgkin disease, ALCL . others);
may arise before, during or after LyP diagnosis;
recommend Q6-12mo followup to assess for development
of malignant lymphoma
■
Fascin, TGF-b pathway, CD30 promotor alterations all
a/w hrisk of associated malignant lymphoma (MF,
ALCL, HD, etc.)
■
Editor note (TH): I often wonder if LyP is not truly a
disease sui generis, but rather a “clinical reaction pattern” or
clinical phenotype that arises when a “pre-lymphomatous
cell” with some oncogenic driver mutation for lymphoid
cells attempts to grow into a full-blown lymphoma but
lacks the necessary “second-hit” (may be one of the genes
already shown to be a/w hrisk of developing a secondary
malignant lymphoma) n without a second-hit, the lesion
regresses/is partially killed off by the patient’s immune
system n clinical lesion regression. This could explain
why LyP has one common clinical presentation despite
having many histological variants with vastly different
immunophenotypes, and why multiple distinct types of
malignant lymphomas have been seen to arise in
association with LyP. In fact, some experts have recently
raised concern that Type B LyP may be better classied
as papular MF. I think it is possible that LyP may just be
a “common clinical phenomenon” that can be seen
during the progression of multiple distinct types of
malignant lymphomas early in their tumorigenesis
(“lymphomagenesis”) when they have enough “juice” to
get started (papules, nodules), but not enough to keep it
going, so they regress. Over time, perhaps some of these
aspiring lymphomas develop the necessary second-hit that
allows them to become full-edged MF or pcALCL. Further
research and time will tell!
• Treatment: only treat if symptomatic, because treatment
does not prevent secondary lymphomas; MTX → dramatic
improvement in 90% (recurs within weeks of stopping),
phototherapy is also rst line; brentuximab can be used if
the former therapies are ineffective
• Boards pearls
■
Type A LyP is distinguished from PLEVA by presence of
large CD301 cells, and “dirty inltrate” containing
numerous eosinophils (never seen in PLEVA) and
neutrophils
■
25% have antecedent, concurrent, or subsequent
malignant lymphomas (MF . ALCL, Hodgkin
lymphoma . others)
■
Dermal hypersensitivity reactions (scabies, bug bites,
and drug reactions) often have scattered CD301 cells
→ may histologically mimic LyP
Primary cutaneous anaplastic large cell
lymphoma (pcALCL)
• Must exclude systemic ALCL!!!
• Solitary (.multiple [20%]), growing, ulcerated tumors up
to 10 cm (larger than LyP); usually adults, M . F; unlike
LyP, lesions do not rapidly “come and go”
• Frequently persists/relapses in skin; infrequent nodal
involvement (10%)
• Histology: sheets of large, atypical CD30
comprising . 75% of inltrate
1
lymphocytes
• Usually lack ALK translocations (vs. systemic ALCL);
EMA negative as well
• 6p25.3 rearrangements (DUSP22-IRF4) predicts good
prognosis in systemic ALCL; found in 25%–30% of pcALCL
• Very good prognosis (90% 5-year survival)
■
Features a/w poor prognosis: older age, generalized
skin involvement, no spontaneous remission, leg
involvement/extensive regional single-limb disease,
solid organ transplant
• Treatment: surgical excision or radiation (rst-line);
low-dose MTX (second-line); Brentuximab vedotin
(anti-CD30 antibody) is a good option in recalcitrant
cases or for spread to lymph nodes
Subcutaneous panniculitis-like T-cell
lymphoma (SPTCL)
• Lymphoma composed of CD4–/ CD81/ CD56–/ TIA11/
Granzyme B1 (cytotoxic) T lymphocytes with a/b phenotype
■
Category previously included aggressive forms now
re-classied as g/d-delta T-cell lymphoma (universally
fatal)
372
6.10 Fibrohistiocytic Neoplasms
• Any age affected; generalized subcutaneous nodules on
legs and trunk; lesion regression n focal lipoatrophy;
systemic symptoms may occur (e.g., fever, weight loss,
h LFTs, cytopenia)
• Histology: subcutaneous lobular inltrate of neoplastic
T cells that “rim” adipocytes; prominent necrotic debris
and cytophagocytosis (“beanbag cells”); lacks interface
changes at DEJ and angiodestruction (vs. g/d-delta T-cell
lymphoma); lacks nodular lymphoid aggregates and
germinal center formation (vs. lupus profundus)
• Good prognosis (80% 5-year survival), but 15% develop
hemophagocytic lymphohistiocytosis (high mortality,
may be a/w HAVCR2 mutations);
• Treatment: steroids, MTX, cyclosporine
Primary cutaneous g/d T-cell
lymphoma
• Aggressive CD4 /CD8 (“double negative”) T-cell
lymphoma w/ expression of g/d T-cell receptor and
cytotoxic markers (CD561, TIA-11, granzyme B1, and
perforin1)
■
b-F1 negative (vs. SPTCL, which is b-F11), TCR-d
positive
• Multiple eroded nodules and plaques 1 visceral involvement
• Histology: dense dermal and subcutaneous lymphoid
inltrate w/ epidermotropism, lichenoid interface
changes (major clue), vascular destruction, 1/– fat
rimming (mimicking SPTCL)
■
Lichenoid interface changes distinguish from SPTCL
(which never has epidermal involvement)
■
Lupus profundus is extremely hard to distinguish →
g/d stain is helpful; also lupus tends to have reactive
lymphoid follicles with clusters of CD1231
plasmacytoid dendritic cells (not seen in g/d TCL)
• Rapidly fatal
Extranodal NK/T-cell lymphoma,
nasal type
1
• EBV
lymphoma with NK phenotype
• Abrupt onset of ulcerated tumors, most commonly on
nasal region
• Histology: variably sized neoplastic cells with prominent
vascular destruction, 1/– epidermotropism
• CD21/CD561 and CD31 (cytoplasmic, not surface)
• Usually fatal
Aggressive epidermotropic cytotoxic
(CD81) T-cell lymphoma
Primary cutaneous CD4-positive small/
medium pleomorphic T-cell
lymphoproliferative disorder
• Presents as a solitary plaque or nodule on the head/neck
(.upper trunk) with an excellent prognosis
• Histology: dense dermal/subcutaneous inltrate of small
to medium lymphocytes; minimal to no
epidermotropism; MF-like immunophenotype (CD4
CD8
/CD30 )
1
/
• Histology and immunophenotype indistinguishable from
tumor stage MF → need clinical correlation (lacks preceding
MF patches/plaques)
CD81 acral T-cell lymphoma
• Usually 1 or a few nodules on acral sites
• Histology: dense dermal inltrate of small-to-medium
atypical lymphocytes (CD31, CD81, TIA-11) with
nuclear atypia; no epidermotropism; perinuclear dot
pattern with CD68 stain
• Indolent course with good prognosis; surgical excision or
radiotherapy if needed
Primary cutaneous B-cell neoplasms
• B-cell neoplasms limited to the skin after systemic workup
(except intravascular B-cell lymphoma); relatively less
common than T-cell neoplasms
• IgH clonality studies are useful in differentiating low-grade
B-cell lymphomas from cutaneous lymphoid hyperplasia
• Typically CD201 and CD79a1 (Table 6.7)
Leukemia cutis
• Most commonly acute myeloid leukemia (AML)
■
Generally there is preceding marrow and peripheral
blood involvement, but aleukemic forms can occur
• Violaceous papules and nodules at any location
• Skin involvement is most common with myelomonocytic
and monocytic types
• Histology: Grenz zone, diffuse dermal inltrate
of myeloid blasts (monotonous cells with high
N:C ratio and ne chromatin); may be seen in sheets,
nodules, perivascularly, or as inltrative cords
(“Indian-ling”)
• MPO1, CD117 (c-KIT)1, CD131, CD331, and
CD341
• Boards fodder: chloromas 5 green nodules in the setting
of AML, because of myeloperoxidase activity
• Old name 5 Ketron-Goodman type of pagetoid
reticulosis
• Eruptive ulcerated tumors with visceral involvement
• Histology: malignant, cytotoxic, CD81 inltrate with
prominent epidermotropism and angiodestruction
■
Histologically indistinguishable from other
epidermotropic CD81 lymphomas (MF, pagetoid
reticulosis, and type D LyP) → distinction best made
clinically
• Usually fatal
6.10 FIBROHISTIOCYTIC NEOPLASMS
Dermatobroma (DF)
• Common benign brohistiocytic lesion; favors adults
(F . M); most commonly on lower extremities
• Firm dermal papules w/ overlying pigmentation and
“dimple” sign (moves downward when pinched)
• Unclear pathogenesis, may be related to prior trauma/bug
bite
373
CHAPTER 6 • Neoplastic Dermatology
Table 6.7 Cutaneous B-Cell Lymphomas
Clinical Features Histopathologic Features
Primary cutaneous
follicle center cell
lymphoma
Primary cutaneous
marginal zone
lymphoma
Primary cutaneous
diffuse large B-cell
lymphoma, leg type
Intravascular B-cell
lymphoma
Violaceous, usually solitary papule or nodule on the
scalp/forehead or back (“Crosti lymphoma”);
excellent prognosis
Purple to brown nodule on the upper extremities or
trunk; excellent prognosis
Elderly, F . M; red to brown nodule on distal
extremity (leg #1), but can occur at other sites;
must exclude systemic disease; less favorable
prognosis (5-year survival 5 50%)
Purple patches and plaques; trunk/thighs; usually
systemic involvement including CNS (→ neuro
deficits), but can be limited to the skin
Irregularly shaped neoplastic follicles; lacks a well-dened mantle zone and
tingible body macrophages
-Usually lacks t(14;18) IgH-Bcl-2 translocation characteristic of systemic
follicular lymphoma
-BCL-6(1) and BCL-2(–)
-Boards Mnemonic: Severity of cutaneous B-Cell lymphomas correlates
with their “BCL score:” Marginal zone lymphoma (least dangerous, lowest “BCL score” 5 2, because BCL-2 1) , Primary cutaneous follicle
center cell lymphoma (second least dangerous, second lowest “BCL
score” 5 6, because BCL-61) , pcDLBCL (highest danger level, highest
“BCL score” 5 8, because BCL-21 and BCL-61)”
Nodular dermal inltrate with prominent monocytoid B cells (small lympho-
cytes with clear halo) and often numerous plasma cells (major clue),
some with Dutcher bodies
-BCL-6(–) and BCL-2(1)
Dense sheets of large round, markedly atypical lymphocytes w/ mitoses
and apoptotic debris in dermis and possibly subcutis; Grenz zone
-Bcl-21, BCL-61 (most cases), and MUM-1 1
Large atypical CD201 B lymphocytes within vessels
• Histology: dermal spindle cell proliferation with
whorled/curlicue pattern, peripheral collagen trapping,
admixed inammatory cells, Touton-type giant cells that
may contain hemosiderin, overlying epidermal
hyperplasia (“tabled rete”), basal hyperpigmentation and
folliculosebaceous induction (Boards tip—induction
may resemble supercial BCC!!!); frequently abuts but
never deeply inltrates fat
■
Immunophenotype:
Positive: Factor XIIIa, CD10 (strong, diffuse),
stromelysin-3 (distinguishes from DFSP)
Negative: CD34, S100, and pan-keratin
• Key distinguishing features of DF (vs. DFSP):
■
Collagen trapping (best appreciated at periphery)
■
Touton-type giant cells and foamy histiocytes (never
seen in DFSP)
■
Hemosiderin-laden histiocytes/Touton giant cells
(never seen in DFSP)
■
DF only “irts” with upper part of fat, but never
penetrates it deeply (Fig. 6.35)
■
Epidermal and folliculosebaceous induction (rarely
seen in DFSP)
■
Factor XIIIa1, stromelysin-31, and CD34 negative
• DF variants:
■
Cellular DF: ↑ cellularity, cells arranged in longer
fascicles; more mitoses; most common type to be
confused w/ DFSP (see above clues)
■
Hemosiderotic: prominent hemosiderin and small
blood vessels
■
Lipidized/xanthomatous: prominent foam cells
■
Aneurysmal: large cavernous vascular spaces;
clinically worrisome for melanoma or malignant
vascular lesion
■
DF with “monster” cells: contains large, bizarre, and
highly pleomorphic cells; mitoses are rare, never see
atypical mitoses
• ↑ Risk of local recurrence w/ aneurysmal, atypical, and
cellular DFs → re-excision recommended
Fig. 6.35 Cellular dermatobroma (cellular benign brous histiocytoma). Stellateshaped lesion that extends into the supercial subcutis along brous septa.
(From Buehler F, Billings SD. Soft tissue tumors and tumor-like reactions. In:
Busam KJ, ed. Dermatopathology: A Volume in the Series: Foundations in Diag-
nostic Pathology. 2nd ed. Philadelphia: Elsevier; 2016:513–594.)
Dermatobrosarcoma protuberans
• Tumor of intermediate malignant potential characterized
by t(17;22) COL1A1-PDGFB fusion
■
Most common abnormality: supernumerary ring
chromosomes (chr22 most commonly)
• Young to middle-aged adults; M F; favors trunk (shoulder
#1), proximal extremities, and groin » head/neck
• Mnemonic: “DFSP affects people 17 to 22 years old
Called Pat” → helps remember young age (17–22) and
the order of the fused genes (17 5 COL1A1; 22 5 PDGFB)
• Firm plaque that expands and develops multinodular
appearance (Fig. 6.36)
374