Page 45 - The Netter Collection of Medical Illustrations - Integumentary System_ Volume 4 ( PDFDrive )

Plate 2-18 Benign Growths

LEIOMYOMA Glycogen formation and breakdown
Gut Specific Pentose shunt
P
Cutaneous leiomyomas are uncommon benign tumors Hexokinase P 6-Phosphogluconic acid
of the arrector pili muscle of the skin. They can occur Glucose Glucose–6–phosphate
as a solitary tumor or as multiple lesions. Both types Transport Glycolysis Pentose phosphate
can be associated with underlying genetic defects. This Glucose system Fructose–6–phosphate
occurs more commonly in multiple cutaneous leiomyo- Fat formation and breakdown
matosis, and one needs to look for systemic findings in Phosphoglyceraldehyde Phosphoglycerol
affected patients. Other muscle sources of cutaneous
leiomyoma formation include the smooth muscle of
blood vessel walls and the dartos muscle. These rare Pyruvic acid Lactic acid
forms of cutaneous leiomyomas are named angioleio-
myomas and solitary genital leiomyomas, respectively.
Clinical Findings: Leiomyomas manifest as dermal Acetyl CoA CH 3 CO CoA
papules or nodules with a slight hyperpigmentation of
the overlying epidermis. They can also have a reddish Oxidative break-
or brownish hue. The tumors are 1 to 2 cm in diameter. down (Krebs or
They occur equally in males and females and affect all tricarboxylic acid Malonyl CoA Aceto–acetyl CoA
races. They may occur anywhere on the skin, but the cycle)
anterior chest and the genital region are two of the
more common areas of involvement. They typically are Circulation Oxaloacetic
tender, and they can be painful. Most leiomyomas acid COOH CH 2 COOH
_
_
become more painful and more sensitive over time. _ CH 2 HO C COOH Citric
acid
_
Cold temperatures have been shown to exacerbate the CO CH 2 COOH
_
pain. The leiomyomas exhibit the pseudo-Darier’s sign. COOH 2CO
This sign is elicited by rubbing the leiomyoma; on 2
manipulation, the lesion begins to twitch or fasciculate. 2H O C COOH -Keto-
It does not form an urticarial plaque as would be seen COOH 2 H C _ glutaric
_
2
with a true Darier’s sign (e.g., in cutaneous mastocyto- Malic _ CH 2 CH 2 COOH acid
_
sis). Malignant transformation is exceedingly rare. acid HO CH
_
Multiple cutaneous leiomyomas occur most com- COOH COO
monly on the trunk and proximal extremities. They are _ COOH
_
the same size as their solitary counterparts, but they can HO C H _ CH 2
_
become so numerous that they appear to coalesce into Fumarate H C H CH 2 Succinic
_
_
large plaques. In most patients, onset occurs in the third hydratase COO COOH acid
enzyme
to fifth decades of life. There is a definite autosomal Palmityl
dominant inheritance pattern to multiple cutaneous Albumin CoA
leiomyomas. These patients have a genetic defect in the Fatty acid
FH gene (also called MCUL1), which encodes the Krebs (NEFA) Fatty acid
cycle protein fumarate hydratase. The fumarate hydra- Triglyceride
tase protein has been found to have tumor suppressor
functions. Many different types of mutations have been
described, ranging from frameshift mutations to dele-
tion of entire genes. This most likely explains the variety
of phenotypes seen. The most concerning and life-
threatening aspect of this mutation is the possibility of
developing an aggressive and deadly form of papillary
renal cell carcinoma. This tumor in patients with mul-
tiple cutaneous leiomyomas tends to be highly aggres-
sive and metastasizes early. Early screening of the patient
and genetic screening of family members may help
decrease the risk of metastatic renal carcinoma. Patients
should be evaluated routinely for kidney disease.
The term Reed syndrome is used to denote women
with cutaneous leiomyomas and uterine leiomyomas.
Pathogenesis: Solitary leiomyomas not associated Low power. Tumor is located within the High power. Spindle cells are bland
with the fumarate hydratase protein defect are believed dermis and is composed of interlacing appearing with blunt-tipped ends.
to be caused by an abnormal proliferation of myocytes. fascicles of spindle-shaped muscle cells.
The cause for this proliferation is unknown. Fumarate
hydratase mutations result in a lack of tumor suppressor
function. The role of this tumor suppressor protein in
the production of multiple leiomyomas has yet to be the myocyte. Immunohistochemical staining can be frequently. Doxazosin and phenoxybenzamine have
determined. used to help differentiate difficult tumors. Leiomyomas both been successful. Calcium channel blockers such as
Histology: The tumor is located within the dermis stain with muscle markers such as smooth muscle actin. nifedipine have also been successful anecdotally. Gaba-
and is composed of interconnected fascicles of spindle- The overlying epidermis is usually normal. pentin and botulinum toxin have been reported to help.
shaped cells. The cells are arranged in a whorl-like Treatment: Surgical excision of the solitary form Surgical excision is warranted for any lesion that is
pattern. The cells are uniform and bland appearing. of leiomyoma is curative. Multiple cutaneous leiomyo- painful and not responding to therapy. Patients with
Mitosis should be absent. The cells have been described matosis can be treated with a number of medications multiple cutaneous leiomyomas should be evaluated for
as cigar shaped, meaning that they have a long, plump to help control the discomfort and pain. Use of α 1 - the genetic defect in the fumarate hydratase protein and
central region with blunt tip ends. The cell of origin is adrenergic receptor blockers has been reported most should have appropriate screening for kidney disease.
THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 31